Calculate in- and exclusion criteria and age groups
Source:R/f_trialPopulation.R
f.trialPopulation.RdTrial concept calculated: inclusion and exclusion criteria as well as age groups that can participate in a trial, based on protocol-related information. Since CTGOV uses single text field for eligibility criteria, text extraction is used to separate in- and exclusion criteria. (See dfMergeVariablesRelevel with an example for healthy volunteers.)
Arguments
- df
data frame such as from dbGetFieldsIntoDf. If `NULL`, prints fields needed in `df` for calculating this trial concept, which can be used with dbGetFieldsIntoDf.
Value
data frame with columns `_id` and new columns: `.trialPopulationAgeGroup` (factor, "P", "A", "P+A", "E", "A+E", "P+A+E"), `.trialPopulationInclusion` (string), `.trialPopulationExclusion` (string).
Examples
# fields needed
f.trialPopulation()
#> $euctr
#> [1] "e3_principal_inclusion_criteria"
#> [2] "e4_principal_exclusion_criteria"
#> [3] "f111_in_utero"
#> [4] "f112_preterm_newborn_infants_up_to_gestational_age__37_weeks"
#> [5] "f113_newborns_027_days"
#> [6] "f114_infants_and_toddlers_28_days23_months"
#> [7] "f115_children_211years"
#> [8] "f116_adolescents_1217_years"
#> [9] "f11_trial_has_subjects_under_18"
#> [10] "f12_adults_1864_years"
#> [11] "f13_elderly_65_years"
#>
#> $ctgov
#> [1] "eligibility.criteria.textblock" "eligibility.maximum_age"
#> [3] "eligibility.minimum_age"
#>
#> $ctgov2
#> [1] "protocolSection.eligibilityModule.maximumAge"
#> [2] "protocolSection.eligibilityModule.minimumAge"
#> [3] "protocolSection.eligibilityModule.eligibilityCriteria"
#> [4] "protocolSection.eligibilityModule.stdAges"
#>
#> $isrctn
#> [1] "participants.ageRange" "participants.inclusion" "participants.exclusion"
#>
#> $ctis
#> [1] "ageGroup"
#> [2] "authorizedPartI.trialDetails.trialInformation.eligibilityCriteria.principalInclusionCriteria.principalInclusionCriteria"
#> [3] "authorizedPartI.trialDetails.trialInformation.eligibilityCriteria.principalExclusionCriteria.principalExclusionCriteria"
#> [4] "authorizedApplication.authorizedPartI.trialDetails.trialInformation.eligibilityCriteria.principalInclusionCriteria.principalInclusionCriteria"
#> [5] "authorizedApplication.authorizedPartI.trialDetails.trialInformation.eligibilityCriteria.principalExclusionCriteria.principalExclusionCriteria"
#>
# apply trial concept when creating data frame
dbc <- nodbi::src_sqlite(
dbname = system.file("extdata", "demo.sqlite", package = "ctrdata"),
collection = "my_trials", flags = RSQLite::SQLITE_RO)
trialsDf <- dbGetFieldsIntoDf(
calculate = "f.trialPopulation",
con = dbc)
#> Querying database (26 fields)...
trialsDf
#> _id .trialPopulationAgeGroup
#> 1 12949496 P
#> 2 13281214 P
#> 3 17473621 P
#> 4 2012-003632-23-CZ P+A
#> 5 2012-003632-23-SE P+A
#> 6 2014-002606-20-PT P
#> 7 2014-003556-31-GB P
#> 8 2014-003556-31-SE P
#> 9 2022-500244-37-00 A+E
#> 10 2022-501142-30-00 A
#> 11 2023-505613-24-00 P
#> 12 2023-508143-51-01 A+E
#> 13 2024-510663-34-00 P
#> 14 20343063 P
#> 15 61070850 P
#> 16 76463425 P
#> 17 80181452 P
#> 18 88261002 P
#> 19 NCT00617929 P+A+E
#> 20 NCT01125800 P+A
#> 21 NCT01483820 P+A
#> 22 NCT01505608 P+A
#> 23 NCT01592045 P
#> 24 NCT02620761 P
#> 25 NCT03280147 P
#> 26 NCT03325439 P
#> 27 NCT03431558 P
#> 28 NCT03876704 P
#> 29 NCT04001712 P
#> 30 NCT04041765 P
#> 31 NCT05969327 P
#> .trialPopulationInclusion
#> 1 All infants with a gestation ≥ 34 weeks and a birth weight ≥ 2000 grams admitted to the neonatal intensive care unit with a clinical diagnosis of PPHN, and commenced on iNO will be deemed potentially eligible for this study. The process of iNO initiation in PPHN on clinical grounds is standardised in the NICUs. In addition, the infants must satisfy the following criteria: 1. ≤ 10 postnatal days of life and within 24 hrs of admission 2. Echocardiography diagnosis of PPHN (see below)3. Absence of significant congenital heart defect excluding a small atrial septal defect or ventricular septal defect (measuring less than 3mm) 4. Indwelling arterial line; oxygenation index ≥25 on at least two consecutive arterial blood gas samples at least 20 minutes apart
#> 2 All infants aged less than 29 weeks admitted to the NICU with a PDA identified on echocardiography between 36 and 48 hours of life will be eligible for inclusion. A comprehensive assessment of PDA significance will be performed using echocardiography to derive a PDA risk score based using a mathematical formula:(Gestation in weeks × -1.304) + (PDA diameter in mm × 0.781) + (Left ventricular output in ml/kg/min × 0.008) + (maximum PDA velocity in m/s × -1.065) + (LV a` wave in cm/s × -0.470) + 41, where 41 is the constant of the formulaInfants with a risk score ≥ 5.0 are deemed to be at high risk of developing CLD/death and will be randomised to either arm.
#> 3 1. Infants with gestational age ≥ 35 weeks and birth weight ≥ 2000 grams (p25)2. Postnatal age > 24 hours – 14 days3. No history of birth trauma/cephalhematoma/bleeding4. Total serum bilirubin levels are 10 and less than19 mg/dl (cut-off value for medium risk infants, gestational age 35-36 6/7 weeks and fit), and radar serum bilirubin total 12 less 22 mg/dl (limit value lower risk infants aged ≥ 38 weeks and fit)5. Asian race6. No circulatory disturbances, respiratory disorders, and saturation above 90%7. The patient's parents/guardians agree to participate in the study and sign an informed consent
#> 4 1. Primary HLH patients of both genders, up to and including 18 years at diagnosis, who have been previously treated by conventional therapy, and who present a reactivation of the disease. 2. Patients must also: - Present reactivation or Worsening, or No Further Improvement of the disease for at least 4 weeks from initiation of treatment after having achieved at least Partial or Incomplete Response see definitions in Table 1 OR b. Show No Response for at least 2 weeks from initiation of treatment or Worsening of the disease see definitions in Table 1 OR c. Show Intolerance to conventional treatment of HLH, as judged by the treating physician 3. Diagnosis of primary HLH according to the following criteria as per the HLH-2004 protocol: a. A molecular diagnosis or familial history consistent with primary HLH, or b. Five out of the eight criteria below are fulfilled: - Fever - Splenomegaly - Cytopenias affecting 2 of 3 lineages in the peripheral blood haemoglobin 90 g/L platelet 100 x 109/L neutrophils 1 x 109/L - Hypertriglyceridemia fasting triglycerides 3 mmol/L or 265 mg/dL and/or hypofibrinogenemia 1.5 g/L - Haemophagocytosis in bone marrow, spleen or lymph nodes with no evidence of malignancy - Low or absent natural killer NK-cell activity - Ferritin 500 mg/L - Soluble CD25 sCD25 i.e. soluble IL-2 receptor 2400 U/mL. In case the diagnosis of HLH is based on the 5 of the 8 above criteria and not on a molecular finding or a familial history consistent with primary HLH, the patient is eligible to enter the study if there is a. Reactivation, or Worsening, or No Further Improvement for at least 4 weeks from initiation of treatment of the disease after having achieved at least Partial or Incomplete Response see definitions in Table 1. In this specific situation, Worsening and No Further Improvement must include abnormal sCD25 or ferritin 2000 ng/ml OR a.b. No Response for at least 2 weeks from initiation of treatment or Worsening of the disease without previous Partial or Incomplete Response. Soluble CD25 must be abnormal or ferritin 2000 ng/ml and the evaluation and approval by the Scientific Steering Committee is mandatory see definitions in Table 1 OR b.c. Intolerance to conventional treatment of HLH, as judged by the treating physician and approval by the Scientific Steering Committee is mandatory 4. Patients must have received treatment for HLH according to the conventional therapy at the site e.g. corticosteroids alone or in combination with etoposide, cyclosporin, methotrexate etc.. At the time of enrollment, eligible patients might still be receiving treatment induction or maintenance or might have already discontinued it. 5. Informed consent signed by the patient if 18 years old, or by the patients legal representatives with the assent of patients who are legally capable of providing it. 6. Having received guidance on contraception for both male and female patients sexually active and having reached puberty: Female of child-bearing potential, having a negative urine pregnancy test at screening, unless true abstinence is in line with the preferred and usual lifestyle of the patient, must agree to use adequate methods of birth control from screening until 6 months after receiving last dose of the study drug. Men with partnerss of child-bearing potential must agree to take appropriate precautions to avoid fathering a child from screening until 6 months after receiving last dose of the study drug.
#> 5 1. Primary HLH patients of both genders, up to and including 18 years at diagnosis of HLH, or at an age appropriate to be treated in the investigators practice. The diagnosis must be made on the following criteria as per HLH-2004 protocol: a. A molecular diagnosis or familial history consistent with primary HLH OR b. 5 out of 8 criteria below are fulfilled: - Fever - Splenomegaly - Cytopenias affecting 2 of 3 lineages in the peripheral blood hemoglobin 90g/L platelets 100x109/L neutrophils 1x109/L - Hypertriglyceridemia fasting triglycerides 3mmol/L or 265mg/dL and/or hypofibrinogenemia 1.5g/L - Hemophagocytosis in bone marrow, spleen or lymph nodes, with no evidence of malignancy - Low or absent natural killer NK-cell activity - Ferritin 500g/L - Soluble CD25 sCD25 i.e. soluble IL-2 receptor 2400U/mL 2. Presence of active disease as assessed by treating physician 3. Patients having already received HLH conventional therapy must fulfill one of the following criteria as assessed by the treating physician: - Having not responded - Having not achieved a satisfactory response - Having not maintained a satisfactory response - Showing intolerance of conventional HLH treatment At the time of enrollment, eligible patients might still be receiving treatment induction or maintenance or might have discontinued it. 4. Informed consent signed by the patient if 18 years old or by their legally authorized representatives with the assent of patients who are legally capable of providing it. 5. Having received guidance on contraception for both male and female patients sexually active and having reached puberty: Females of child-bearing potential, having a negative pregnancy test at screening and unless true abstinence is in line with the preferred and usual lifestyle of the patient, must agree to use adequate methods of birth control from screening until 6 months after receiving last dose of the study drug. Males with partners of child-bearing potential must agree to take appropriate precautions to avoid fathering a child from screening until 6 months after receiving last dose of the study drug.
#> 6 1. Children 3 months to 18 years of age with a minimum weight of 6 kg at the time of randomization. An approved protocol will be implemented prior to enrolment of each subsequent age group. 2.Presence of an index VTE which is confirmed by imaging. Index VTE include, but are not limited to, deep vein thrombosis, pulmonary embolus, cerebral sinovenous thrombosis, renal vein thrombosis, portal vein thrombosis, and splanchnic thrombosis. 3.Intention to manage the index VTE with anticoagulation treatment for at least 12 weeks or intention to manage the index VTE with anticoagulation treatment in neonates for at least 6 weeks. 4.Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative has been informed of all pertinent aspects of the study. Depending on local regulations, whenever the minor is able to give assent, the minors assent must also be obtained. 5.Subjects/legally acceptable representatives who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 6. For women of childbearing potential: agreement to remain abstinent refrain from heterosexual intercourse or use highly effective method of contraception throughout the study and for at least 33 days 5 half -lives plus 30 days after the last dose of assigned treatment.
#> 7 Each subject must meet the following criteria to be enrolled in this study. 1. Subject was randomized in Study ROPP-2008-01, Section D 2. Subjects parent or legally authorized representatives must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the subject.
#> 8 Each subject must meet the following criteria to be enrolled in this study. 1. Subject was randomized in Study ROPP-2008-01, Section D 2. Subjects parent or legally authorized representatives must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the subject.
#> 9 Diagnosis of symptomatic COVID-19 of less than 5 days’ duration, with at least 1 point in at least 4 items of the symptom evaluation table, and at least 2 points in at least 2 items, OR a minimum total score of 6 points (Table 1) / Diagnosis of COVID-19 confirmed in the last 48 hours by a positive test for SARS-CoV-2 RNA by RT PCR or a rapid validated antigen test (excluding self-test), in a specimen from the upper respiratory tract, the saliva (antigen test), the lower respiratory tract or an expectorated sputum / No indication that the patient will be hospitalized in the next 48 hours for COVID-19 related reasons / Adult male or female patients aged ≥ 18 years / Females must have a negative pregnancy test or must be post-menopausal / Able to understand and willing to sign an IRB/IEC approved written informed consent document. / Able to understand and be available for daily phone calls to evaluate symptoms.
#> 10 Age > 18 years old / Pregnant, Gestational age ≥ 37 weeks / Singleton pregnancy with cephalic presentation / Nulliparous / PROM without labour beyond 12 hours / Unfavourable cervix (Bischop score < 6) / Able to give her informed consent / Ability to comply with the requirement of the study / Covered by the French Social Security welfare system
#> 11 Panel A: Is undergoing treatment for possible, probable, or proven invasive fungal infection (IFI) known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (which can include candidiasis) / Panel B: has an investigator-assessed diagnosis of possible, probable, or proven IFI known or suspected to be cause by fungal pathogens against which POS has demonstrated activity (and cannot include candidiasis) / Has a central line (eg, central venous catheter, peripherally-inserted central catheter) in place or planned to be in place before beginning IV study intervention / Has a body weight of ≥500 g / The participant (or legally acceptable representative) has provided documented informed consent for the study.
#> 12 In order to be eligible to participate in this study, a subject must meet all of the following criteria: •\tCervical SCI neurological level C1-Th1, •\tFunctionally hindering generalized spasticity of the upper extremities with insufficient effect or too many side effects of oral spasmolytics and/or local treatments •\tAmerican Spinal Injury Association (ASIA) Impairment Scale: A,B,C,D •\t> 1 year after onset of SCI •\tOver 18 years old •\tNo progressive disease •\tStabile medical situation for undergoing the ITB-trial and a final implantation of a baclofen pump after positive test •\tNo muscle or nerve blocks < 6 months for start of study
#> 13 Age. Neonates and infants who are aged less than 6 months (corrected age) at the time of the informed consent signed by legally acceptable representative (LAR) of minors. Preterm neonates and infants will be eligible for inclusion but must have reached Post-Menstrual Age (PMA) of at least 28 weeks. / Participants who are hospitalised with influenza infection, confirmed by a positive rapid molecular diagnostic test for influenza, or a local quantitative RT-PCR test and who must have a potential for improvement. Subjects with negative rapid molecular test result suspected of having influenza can be enrolled following confirmatory testing by quantitative RT-PCR. / Weight. Body weight ≥1kg. / Sex. Male or female. / Informed Consent Legally acceptable representative (LAR) of minors are willing and able to give written informed consent to participate in the study (or included as permitted by local regulatory authorities, IECs or local laws).
#> 14 1. Preterm infants less than 1800 g birth weight, either sex2. Infants with gestational age less than 32 weeks (depending FUR)
#> 15 1. Both male and female infants, aged less than 28 days2. Hospitalised in the Intensive Care Unit (ICU) or Neonatal Intermediate Care Unit (NICU) 3. Weight less than 1500 g at birth4. Fed exclusively via enteral route5. Haemodynamic stability (arterio-venous 3 - 5) 6. Have not received prior formulas with added energy substrates7. Signed informed consent by parents or guardians
#> 16 1. Gestational age at birth <32 weeks, or birth weight <1,500 g2. The infant is receiving ≤30 ml/kg/day of milk at randomisation 3. Written informed parental consent is obtained To ensure the widest applicability to preterm infants across the UK, those exclusively breast milk fed, formula milk fed, or receiving mixed feeds will be included.
#> 17 1. Gestational age of 23 0/7 - 27 6/7 weeks2. Postnatal age less than 12 hours3. Necessity for any form of positive pressure support (mechanical or nasal ventilation or continuous positive airway pressure [CPAP])4. Singleton or second born in case of multiple pregnancy5. Parental consent for participation
#> 18 Infants will be eligible to participate if:1. Gestational age at birth is less than 32 weeks2. Less than 72 hours old3. Written informed parental consent is obtainedIf infants are receiving antibiotic treatment for suspected or confirmedInfection, they are still eligible for recruitment.
#> 19 * Timing of relevant evaluations: Taking in account the need for rapid intervention, if white blood count is less than 200 on day +20, bone marrow aspirate should be performed on day +21. Unless there is an increase in absolute neutrophil count (ANC) to \\> 500 in the following 7 days, bone marrow aspirate should be repeated on day +28. If the white blood count is still less than 200 and bone marrow is acellular, bone marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and availability of cord blood (CB) units assessed. If the BM or PBSC donor is not confirmed within 14 days of the request for the donation (typically second donation from the same donor), CB unit should be used instead.Primary or secondary graft failure after hematopoietic stem cell transplantation defined as a \\> 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day +42 with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor, hematopoietic cell graft or conditioning regimen should be considered for this study.* primary graft failure is defined as: * ANC \\< 500 * BM \\< 10% on two occasions (Day +21 and Day +28) * Donor chimerism need not to be considered, provided there is no evidence of malignancy* secondary graft failure is defined as \\< 5% cellularity and ANC \\< 500 for more than 7 days any time after primary engraftment). * Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \\[IUD\\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. * Patients or their guardian are able and willing to provide written informed consent.Patient
#> 20 * Phase I - Patients aged ≥12 months and \\<18 years, Phase II - Patients ≥12 months* Phase I - Histologically confirmed diagnosis of medulloblastoma, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, high grade glioma, or osteosarcoma, that has progressed despite treatment with standard therapies, or for which no standard treatments are available (patients with brainstem gliomas are excluded). Phase II - Histologically confirmed diagnosis of recurrent or relapsed medulloblastoma with at least one measurable lesion.* Performance Status: Karnofsky ≥60% for patients \\>10 yrs, Lansky ≥50 for patients less than or equal to 10 yrs* Protocol-defined renal , liver and bone marrow function* Negative pregnancy test before starting study treatment. If of child bearing potential must use 'highly effective' methods of contraception.* All patients must consent to provide a tumor sample
#> 21 * Subjects must have histologically proven neuroblastoma or medulloblastoma and confirmation of refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression* Subjects must be age \\>12 months and diagnosed before the age of 21* Measurable disease, including at least one of the following:* Measurable tumor \\>10mm by CT or MRI* Positive bone marrow biopsy/aspirate.* Positive MIBG* Current disease state must be one for which there is currently no known curative therapy* Lansky Play Score or Karnofsky scale must be more than 30* Subjects without bone marrow metastases must have an ANC \\> 750/μl and platelet count \\>50,000/μl* Adequate Renal Function Defined As* Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or* A serum creatinine based on age/gender* Adequate liver function must be demonstrated, defined as:* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age* SGPT (ALT) \\< 10 x upper limit of normal (ULN) for age* SGOT (AST) \\< 10x upper limit of normal (ULN) for age* No other significant organ toxicity defined as \\> Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE V4.0- http://ctep.cancer.gov/forms/CTCAEv4.pdf)* A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)* Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.* Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines* Subjects may have received microtubulin inhibitors during previous therapies.
#> 22 * Subjects must have histologically proven Neuroblastoma and confirmation of primary refractory or recurrent disease with histologic confirmation at diagnosis or at the time of recurrence/progression. Subjects must have primary refractory or have early relapse disease (early relapse disease is defined as having received ≤ one or two relapse therapies).* Subjects must be age \\>12 months and diagnosed before the age of 21 years* Measurable disease, including at least one of the following:Measurable tumor \\>10 mm by CT or MRI Positive bone marrow biopsy/aspirate Positive MIBG* Current disease state must be one for which there is currently no known curative therapy* Lansky Play Score or Karnofsky scale must be more than 30* Subjects without bone marrow metastases must have an ANC \\> 750/μl and platelet count \\>50,000/μl* Adequate Renal Function Defined As Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or* A serum creatinine based on age/gender table* Adequate liver function must be demonstrated, defined as:Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age SGPT (ALT) \\< 10 x upper limit of normal (ULN) for age SGOT (AST) \\< 10x upper limit of normal (ULN) for age* No other significant organ toxicity defined as \\>Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE V4.0- http://ctep.cancer.gov/forms/CTCAEv4.pdf)* A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)* Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.* Informed Consent: All subjects and/or legal guardians must sign written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines* Subjects may have received microtubulin inhibitors during previous therapies.* Subjects may have received any number of prior biological therapies.
#> 23 * Diagnosis of high-risk neuroblastoma* 8 years of age or younger at diagnosis of high-risk neuroblastoma* Patients must have completed therapy including intensive induction followed by autologous stem cell transplantation (ASCT) and radiotherapy \\* Radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor* Must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases, and bone metastases AND must also meet the protocol specified criteria for bone marrow response as follows: \\* No more than 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy* Patient who have no tumor seen on the prior bone marrow, and then have ≤ 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible* No more than 12 months from starting the first induction chemotherapy after diagnosis to the date of ASCT \\* For patients who became high-risk neuroblastoma after initial non-high risk disease, the 12 months period should start from the date of induction therapy for high-risk neuroblastoma to the date of ASCT* No progressive disease at time of registration except for protocol-specified bone marrow response* Adequate hematological, renal, hepatic, pulmonary and cardiac function* CNS toxicity \\< Grade 2
#> 24 1. Gestational age at birth 23 0/7 to 27 6/7 weeks by best obstetrical dating 2. No previous exposure to indomethacin 3. Clinical determination to use indomethacin to attempt closure of PDA 4. No known congenital abnormalities involving the kidneys, heart or lungs 5. No preexisting renal dysfunction, defined as serum creatinine > 1.0 mg/dl, or urine output <1.0 ml/kg/hour over the previous 24 hours.
#> 25 Inclusion criteria for the initial observation part of study preceding randomization 1. Neonates aged 0-28 days, either inborn or outborn, who are currently admitted in the Neonatal Unit of the centre. 2. Whose birth weight is greater than or equal to1000 grams (it should be reliably ascertained from records of a hospital) 3. Whose residence is within approximately 15 kms from the center, so that the infant can be brought back to the center for follow-up 4. Who have suspected septicemia for which a conventional or BACTEC/BACTALERT blood culture is sent and for which the treating physician decides to start antibiotics Inclusion criteria for Randomization applicable after 7 days of therapy of above patients with sensitive antibiotics: 1. Positive blood culture other than Staphylococcus aureus 2. No signs and symptoms of sepsis from end of day 5 through end of day 7 of starting sensitive antibiotics
#> 26 - Confirmation on video-electroencephalography (VEEG) of >= 2 minutes of cumulative electroencephalographic neonatal seizures (ENS), or >=3 identifiable ENS prior to entering the Evaluation Period, despite receiving previous antiepileptic drug treatment for the treatment of electroencephalographic seizures. The occurrence of ENS during an up to 1-hour period must be confirmed either by the local or central VEEG reader prior to drug administration. Preferably, the central VEEG reader should confirm the required ENS - Subject is male or female and must be at least 34 weeks of corrected gestational age (CGA). In addition, term neonates up to 27 days of postnatal age (PNA) and preterm neonates up to 40 weeks of CGA and 27 days of PNA can be enrolled - Subject weighs at least 2.3 kg at the time of enrollment - Subjects with or without concomitant hypothermia treatment
#> 27 Neonates with: birth weight ≤ 2500 g and ≥ 1000 grams. gestational age ≥ to 28 +0 weeks to 36+6. family planned on staying in the study area for at least 1 month • parents/ caretaker willing to provide consent. newborn initiated enteral feeding via (gavage feeding with expressed breast milk or formula, direct breast feeding or cup and spoon feeding at or within 48 hours of birth.)
#> 28 - admitted to the neonatal intensive care unit (NICU) within 24 hours after birth - gestational age younger than 34 weeks - birth weight less than 1500 gram - informed consent was obtained from the infants' parents or guardians
#> 29 1. Preterm neonates ≤ 33 weeks gestational age. 2. Preterm neonates who need respiratory support (either nasal canula, continuous positive airway pressure (CPAP) or mechanical ventilation).
#> 30 - Very low birth weight infants (< 1500 g) - Gestational age below 32 weeks - Risk of Early-Onset sepsis from maternal and neonate factors - Inborn neonates
#> 31 - -Inclusion Criteria: full term newborns with clinical and laboratory findings of early onset of sepsis (EOS).
#> .trialPopulationExclusion
#> 1 1. Lethal congenital anomalies or obvious syndrome 2. Bleeding diathesis (abnormal coagulation screen/platelet <100,000/ mm3) 3. The presence of Intraventricular haemorrhage4. Diastolic Hypotension (defined as a diastolic blood pressure less than the 3rd centile for any given gestation) unresponsive to medical treatment (≥30 mL/kg fluid bolus and ≥ 2 inotropes of at least 10 μg/ kg/min) 5. Hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia6. Evidence of renal impairment (Creatinine > 100micromol/l) 7. Severe Hypovolaemia: Heart rate > 180, capillary refill > 5 seconds, urine output < 0.5ml/kg/hour, in addition to diastolic hypotension mentioned above
#> 2 1. Lack of consent or study investigators to carry out echocardiogram examination2. Lethal congenital abnormality or obvious syndrome3. Pulmonary hypoplasia4. Known or suspected NEC5. Thrombocytopenia: platelet count < 100/mm26. Impaired renal function creatinine > 100 μmol/L; and/or oliguria < 1ml/kg/hour7. Culture positive sepsis8. Congenital heart disease other than a PDA or a patent foramen ovale9. Active bleeding including grade 3 or higher IVH or gastrointestinal haemorrhage
#> 3 1. Genetic, metabolic disorders, hemolytic anemia (examination of GDS levels, blood group, and rhesus, peripheral blood picture)2. Infection (clinical fever or hypothermia and increased leukocyte laboratory tests)3. The direct bilirubin level exceeds 2 mg/dl or 20% of the total serum bilirubin level
#> 4 1. Diagnosis of secondary HLH consequent to a proven rheumatic or neoplastic disease. 2. Body weight 3 kg. 3. Patients treated with: - any T-cell depleting agents such as anti-thymocyte globulin ATG, anti-CD52 during the previous 2 weeks prior to screening - anti-CD20, as part of EBV infection treatment, within the previous week prior to screening - any other biologic drug within 5 times their defined half-life period a list of some of the most commonly used biologic half-lives will be included in the Study Specific Risk Management Plan. 4. Isolated or multiple acute organ failures heart, lung or kidney requiring aggressive therapy such as high doses of inotropic drugs, circulatory assistance, hemofiltration or haemodialysis, artificial ventilation. 5. Active mycobacteria, Shigella, Campylobacter, Leishmania or Salmonella infections. 6. Evidence of past or active tuberculosis. 7. Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies. 8. History of malignancy. 9. Patient who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function. 10. History of hypersensitivity or allergy to any components of the study regimen. 11. Receipt of a live or attenuated live including BCG vaccine within the last 12 weeks before screening. 12. Pregnant or lactating female patients.
#> 5 1. Diagnosis of secondary HLH consequent to a proven rheumatic or neoplastic disease. 2. Body weight 3 kg. 3. Patients treated with: - any T-cell depleting agents such as anti-thymocyte globulin ATG, anti-CD52 during the previous 2 weeks prior to screening - any other biologic drug within 5 times their defined half-life period, expect for rituximab in case of documented B-cell EBV infection 4. Active mycobacteria, Histoplasma Capsulatum, Shigella, Campylobacter, Leishmania or Salmonella infections. 5. Evidence of history of tuberculosis or latent tuberculosis. 6. Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies. 7. Presence of malignancy. 8. Patient who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function. 9. History of hypersensitivity or allergy to any components of the study regimen. 10. Receipt of a live or attenuated live including BCG vaccine within the last 12 weeks before screening. 11. Pregnant or lactating female patients.
#> 6 1. Anticoagulant treatment for the index VTE for greater than 7 days prior to randomization. 2. Cerebral sinovenous thrombosis in Germany only. 3. Thrombectomy, thrombolytic therapy, or insertion of a caval filter to treat the index VTE 4. A mechanical heart valve 5.Active bleeding or high risk of bleeding e.g. central nervous system CNS tumors at the time of randomization. 6.Intracranial bleed, including intraventricular hemorrhage, within 3 months prior to randomization. 7.Abnormal baseline liver function ALT 3 x upper limit of normal ULN or conjugated bilirubin 2x ULN at randomization. 8.At the time of randomization, inadequate renal function as defined in Section 7.2.2 Estimated Glomerular Filtration Rate Assessment of the protocol. 9.Platelet count 50109 per L at randomization. 10.At the time of randomization, uncontrolled severe hypertension as defined in Section 7.1 Physical Examination of the protocol. 11.At the time of randomization, use of prohibited concomitant medication as listed for apixaban in Section 5.5 Concomitant Medication of the protocol. 12.Known allergy to apixaban. 13.Female subjects who are either pregnant or breastfeeding a child. 14.Geographically unavailable for follow-up. 15.Family members who are either investigational site staff members directly involved in the conduct of this trial or site staff members otherwise supervised by the Investigator. Family members who are Pfizer or Bristol Myers Squibb BMS employees directly involved in the conduct of this trial. 16.Taking an investigational drug in other studies within 30 days before the first dose of apixaban and/or during study participation. N.B. using marketed medications commonly used in usual and customary practice, though not labeled for use in children, is acceptable. 17.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
#> 7 Subjects who meet any of the following criteria will be excluded from the study. 1. Any other condition or therapy that, in the Investigators opinion, may pose a risk to the subject or interfere with the subjects ability to be compliant with this protocol or interfere with the interpretation of results 2. The subject or subjects parent or legally authorized representatives is unable to comply with the protocol as determined by the Investigator
#> 8 Subjects who meet any of the following criteria will be excluded from the study. 1. Any other condition or therapy that, in the Investigators opinion, may pose a risk to the subject or interfere with the subjects ability to be compliant with this protocol or interfere with the interpretation of results 2. The subject or subjects parent or legally authorized representatives is unable to comply with the protocol as determined by the Investigator
#> 9 Patients with an indication for hospitalization (e.g. SpO2 <92%) / Liver enzyme elevation more than 3x above normal in the last 4weeks or at inclusion / Patients who are detained or committed to an institution by a lawcourt or by legal authorities (subject is vulnerable, such as deprived of freedom) / Patients participating in another clinical trial with a new investigational drug or investigational non-drug treatment / Known allergy or intolerance to pamapimod or any other ingredient of the IMP or another P38 inhibitor / Known allergy or intolerance of clinical relevance to pioglitazone or any other ingredient of the IMP. / Patients where oral administration of pioglitazone is contraindicated (i.e. cardiac failure or history of cardiac failure (NYHA stages I to IV),with hepatic impairment, diabetic ketoacidosis, current bladder cancer or a history of bladder cancer, uninvestigated macroscopic haematuria / Any use of CYP450 2C8 inducers (e.g. rifampicin) / Known or suspected active viral (including HIV, hepatitis B, hepatitisC), bacterial, mycobacterial or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected. / Pregnant or breastfeeding women / Any uncontrolled concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements as determined at the discretion of the investigator
#> 10 Unable to understand French language / Known HIV seropositivity / Placenta praevia / Fetal death / Abnormal FHR (Fetal Heart Rate) / Contraindication to misoprostol / Contraindication to balloon / Contraindication to oxytocin / Patient subject to a legal protection order (curatorship or tutorship) / Refusal to participate / Contraindication for vaginal delivery / Loss of meconium amniotic fluid (LA) / Temperature > 38.2°C / Intrauterine infection / IUGR with Doppler anomaly / Fetus with expected polymalformative syndrome / Scarred womb / Suspicion of genital herpes
#> 11 Has received POS within 30 days before Day 1 / Has enrolled previously in the current study and been discontinued / Has QTc prolongation at screening >500 msec / Has significant liver dysfunction / Is hemodynamically unstable, exhibits hemodynamic compromise, or is not expected to survive at least 5 days / Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis. / Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption / Has known or suspected active COVID-19 infection / Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study intervention used / Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT interval (QT) prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of first dose of study intervention / Has received any listed prohibited medications within the specified timeframes before the start of study intervention / Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Panel B) / Has suspected/proven invasive candidiasis (Panel B)
#> 12 A potential subject who meets any of the following criteria will be excluded from participation in this study: •\tPregnancy •\tWomen of child bearing potential •\tNursing women •\tAllergy baclofen •\tContra indication ITB (increased bleeding tendency, increased intracranial pressure, severe pressure ulcer) •\tOral anticoagulants •\tSevere depression •\texcessive alcohol use •\tPatients depending on ventilation •\tNot adequately treated SAS •\tPcCO2 > 6,5 KPa
#> 13 Participants who are known or suspected to be hypersensitive to any component of the study medication. / Participants who, in the judgment of the investigator, are unlikely to complete the course of treatment due to their current disease process. / Liver function: •\tSubjects who meet the following criteria at Baseline: ALT ≥3xULN with Bilirubin ≥2xULN or Isolated bilirubin ≥ 2xULN and >50% direct bilirubin or ALT ≥5xULN Inclusion of subjects with liver function tests that fall outside these criteria must be discussed and agreed with the medical monitor. •\tCurrent or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of benign conditions such as Gilbert's syndrome). Inclusion of subjects with neonatal hyperbilirubinaemia may be considered if appropriately managed according to local guidelines and must be discussed with the medical monitor. / Participants who require concurrent therapy with another anti influenza drug. / Participants who have participated in a study using an investigational drug within 30 days prior to Baseline. / Child in care (CiC), as defined below: •\tA child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. •\tThe definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a CiC does not include a child who is adopted or has an appointed legal guardian. / Patients undergoing treatment by Extracorporeal membrane oxygenation (ECMO) or hemofiltration. / Participants who are positive for SARS-CoV-2, as determined by a diagnostic test, at screening.
#> 14 1. Newborns multiple malformations2. Early neonatal sepsis3. Does not provide consent to participate in the study
#> 15 1. Patients suffering from inborn errors of metabolism in any variant or a disease in itself a negative influence on growth (congenital heart disease, kidney failure, genetic diseases)2. Post-operative state greater than 72 hours
#> 16 1. Infants with a severe congenital anomaly2. Infants who, in the opinion of the treating clinician, have no realistic chance of survival 3. Infants who are unlikely to be traceable for follow-up at 24 months of age (for example, infants of non-UK residents)
#> 17 1. Clinical decision not to administer therapies (infant not considered viable)2. Dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment3. Known or suspected congenital heart disease (not including a persistent ductus arteriosus and/or an atrial septum defect)
#> 18 1. Infants with severe congenital anomalies 2. Anticipated enteral fasting of more than 14 days 3. Infants who, in the opinion of the treating clinician, have no realistic prospect of survival
#> 19 The presence of any of the following excludes a patient from study enrollment:* Uncontrolled active infection defined as more than one week with no response to appropriately chosen antibiotics* Evidence of recurrence of primary malignancy.* Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate methods as described.* Allergy to rituximab.* Evidence of HIV infection or positive HIV serology.* Autologous recovery defined as defined as greater than 90% recipient PCR product in the competitive VNTR PCR performed on gradually increasing white blood cell count.Donor Inclusion Criteria:* Related donors must be 2-75 years of age and in good health.* Meets match criteria* Able and willing to undergo cell collection procedures (bone marrow cell collection or leukapheresis)* Not pregnant or lactating.* HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.* Patients or their guardian are able and willing to provide informed consent
#> 20 * Systemic anti-cancer treatment within 2 weeks prior to first dose (6 weeks for nitrosourea, mitomycin and monoclonal antibodies).* Focal radiotherapy within 4 weeks prior to first dose, or full spinal radiotherapy within 3 months of first dose.* Unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia or other specifications in the eligibility criteria for this study), or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal Investigator (PI) and documented.* Major surgery, serious illness or traumatic injury within 2 weeks of starting study therapy. Patients anticipated to require major surgery within the first 2 cycles of treatment.* Patients requiring a nasogastric tube for drug administration (G-tubes are permitted)* Impaired cardiac function* Pregnant or breast-feeding females* Impairment of gastrointestinal (GI) function or GI diseaseOther protocol-defined inclusion/exclusion criteria may apply
#> 21 * Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects), generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas).* Subjects who have received any myeloablative therapy within the previous 2 months.* Subjects receiving anti-tumor therapy for their disease or any investigational drug concurrently* Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is \\> Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic therapy.* Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a patient's ability to sign or the legal guardian's ability to sign the informed consent, and patient's ability to cooperate and participate in the study* Subjects with known hypersensitivity to any of the components of the drugs to be administered on study
#> 22 * Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects), generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas). Subjects may not have received more than 1 cycle of Irinotecan and Temozolomide as previous relapse therapy.* Subjects who have received any myeloablative therapy within the previous 2 months.* Subjects receiving any investigational drug concurrently* Subjects with serious infection or a life-threatening illness (unrelated to tumor) that is \\> Grade 2 (NCI CTCAE V4.0), or active, serious infections requiring parenteral antibiotic therapy.* Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study* Subjects with known hypersensitivity to any of the components of the drugs to be administered on study.* Subjects who have previously been treated with TPI 287.
#> 23 * Prior anti-GD2 antibody therapy* Prior vaccine therapy for neuroblastoma* Concurrent anti-cancer or immunosuppressive therapy
#> 24 1. Enrollment in concurrent study in which interventions may contribute confounding variables or have competing outcomes 2. Infants with antenatally or postnatally diagnosed renal or urinary tract abnormalities 3. Infants with umbilical cord or infant blood pH below 7.0 at any time before enrollment 4. Attending physician unwilling to have infant participate in study 5. Absence of informed consent
#> 25 Exclusion criteria for the initial observation part of study preceding randomization: 1. Central Nervous System infection (Central Nervous System infection (meningitis will be defined as CSF Cells >25 per uL with polys >60% OR [(CSF glucose <20 mg/dL OR CSF:blood* glu ratio <0.6) AND (CSF protein >150 mg/dL in term OR >180 mg/dL in preterm)] 2. Septic arthritis, osteomyelitis or deep-seated abscess as clinically judged by the treating team 3. Life threatening congenital malformations as judged by the principal investigator of the centre Exclusion criteria for randomization applicable after 7 days of therapy of above patients with sensitive antibiotics: 1. Sterile blood culture 2. Suspected contaminants in blood culture. 3. Growth of Staphylococcus aureus in blood culture 4. Growth of fungal organism in blood culture 5. Diagnosis of meningitis, septic arthritis, osteomyelitis, abscess 6. Has not gone into remission on day 5 or have recurrence of symptoms from day 5 through day 7 7. If the empiric antibiotic is resistant but neonate has shown improvement of signs and symptoms of sepsis and there is ambiguity regarding in vivo sensitivity of antibiotic use
#> 26 Subjects are not permitted to be enrolled in the study if any of the following criteria are met: - Subject receiving antiepileptic drug (AED) treatment other than phenobarbital, midazolam, phenytoin, levetiracetam (≤60 mg/kg/day), or lidocaine for the treatment of seizures prior to or at the time of enrollment (Confirmatory Cohorts only) - Subject with seizures responding to any of the following: previous AED treatment immediately prior to BRV treatment, pyridoxine treatment, or correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) - Subject requires extra corporeal membrane oxygenation - Subject has seizures related to prenatal maternal drug use or drug withdrawal - Subject has known severe disturbance of hemostasis, as assessed by the Investigator - Subject has a poor prognosis for survival, as judged by the Investigator - Subject has 2x upper limit of normal (ULN) of any of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), with the following exception: For subjects with perinatal asphyxia, elevation of AST, ALT or ALP <5x ULN is acceptable, if initial and peak elevation of liver function tests (LFTs) occurs within 5 days after birth, and the time course of LFT elevation is compatible with hepatic injury due to perinatal asphyxia. The determination of ULN will be based on the subject's gestational age (GA) and the site's normal range values for the respective GA - Subject has direct (conjugated) bilirubin levels >2 mg/dL - Subject requiring or expected to require phototherapy or exchange transfusion due to elevated bilirubin - Subject with rapidly increasing bilirubin that may preclude the subject from inclusion in the study at the discretion of the Investigator
#> 27 Neonate with congenital anomalies. early-onset sepsis. birth weight less than 1000 g. gestational age less than or equal to 27weeks+6 days. history of Chorioamnionitis or maternal group B streptococcus colonization. Reversed or absent end-diastolic flow on maternal umbilical artery Doppler where available.
#> 28 - congenital malformation - chromosomal disease, genetic metabolic diseases - the infants or his/mother has abnormal thyroid function or parathyroid gland function - neonatal necrotizing enterocolitis, diarrhea - intracranial hemorrhage of 3 degrees or above - pulmonary hemorrhage - liver enzymes elevated by more than 2 times, cholestasis - death or discharge against medical advice - refuse to take part in the study
#> 29 1. Neonate>33 wks gestational age. 2. Neonates on room air. 3. Neonates with major congenital or cardiac anomalies
#> 30 - Birth weight < 600 g - Gestational age < 26 weeks - Multiple Congenital Anomaly - Neonates with suspected congenital syndrome
#> 31 - Preterm newborn, NPO neonates , infants with maternal risk factors , such as clinical and/or histological chorioamnionitis, neonates delivered at home ,neonates to mothers with premature rupture of membrane, and major congenital abnormalities which may be predisposing factors for development of EOS.