Prophylactic treatment of the ductus arteriosus in preterm infants by paracetamol

Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen - TREOCAPA

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-004297-26-FR

Enrollment

824

Registered

2020-02-28

Start date

2020-04-17

Completion date

Unknown

Last updated

2025-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patent ductus arteriosus

Interventions

Trade Name: Paracetamol Pharmaceutical Form: Solution for infusion INN or Proposed INN: acetaminophen Other descriptive name: PARACETAMOL Concentration unit: mg/kg milligram(s)/kilogram Concentration

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: ? Birth between 23-26 W for Phase II, between 23-28 W for Phase III ? Post natal age =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: ? Parental refusal ? Birth defect / Congenital anomaly ? Twin-to-twin transfusion syndrome ? Suspicion of pulmonary hypoplasia - Suspicion of hepatic impairment (hemorrhagic syndrome and/or severe hypoglycemia) ? Clinical instability that can lead to rapid death ? Impossibility to start treatment before 12 hours of life ? Parents placed under judicial protection ? Participation in other clinical trial using acetaminophen during the first 5 days of life, indomethacin or ibuprofen during the first 3 days of life or using rescue treatment of PDA not recommended in the TREOCAPA trial

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary objectives : Phase II: The objective of Phase II is to define the minimum effective dose of acetaminophen to close the ductus arteriosus before or at day 7 in preterm infants of 23-26 weeks of gestation Phase III: The primary objective is an increase in surviving without severe morbidity at 36 weeks of post menstrual age (or at discharge if it occurs before) from 50% (placebo group) to 60% in group receiving a prophylactic treatment by acetaminophen during the first 5 days of life.;Secondary Objective: Secondary objectives : Phase II: ? Tolerance of acetaminophen at each dose ? Pharmacokinetics of acetaminophen and evaluation of the concentration-response curve (i.e., acetaminophen exposure vs. time to close the ductus arteriosus or decrease the size of ductus). ? To evaluate the relationship between acetaminophen concentration and toxicity occurrence. Phase III: ? Early prophylactic treatment by acetaminophen decreases pain score and opiate consumption during the first 5 days of life. ? Early prophylactic treatment by acetaminophen reduces the number of back-up treatment of PDA (NSAIDs, surgery, trans-catheter procedure) ? Early prophylactic treatment by acetaminophen reduces catecholamines, opioid and parenteral nutrition requirements ? Pharmacokinetics of acetaminophen (in 50 preterms).;Primary end point(s): Primary endpoint of phase II is the closure of Ductus Arteriosus (DA) assessed by echocardiography during the first 7 days of life, defined as DA closed at two consecutive echocardiographies or if the DA is closed at echocardiography of Day 7 Primary endpoint of phase III is the survival without severe morbidity at 36 weeks of post menstrual age or at first discharge home, whichever comes first. The severe morbidities include bronchopulmonary dysplasia (BPD Grade 3 according to NIH consensus), necrotizing enterocolitis (NEC) of Bell's stage II or III, intraventricular hemorrhage (IVH) grade III-IV or cystic leukomalacia observed at a	—

Measure

Time frame

Main Objective: Primary objectives : Phase II: The objective of Phase II is to define the minimum effective dose of acetaminophen to close the ductus arteriosus before or at day 7 in preterm infants of 23-26 weeks of gestation Phase III: The primary objective is an increase in surviving without severe morbidity at 36 weeks of post menstrual age (or at discharge if it occurs before) from 50% (placebo group) to 60% in group receiving a prophylactic treatment by acetaminophen during the first 5 days of life.;Secondary Objective: Secondary objectives : Phase II: ? Tolerance of acetaminophen at each dose ? Pharmacokinetics of acetaminophen and evaluation of the concentration-response curve (i.e., acetaminophen exposure vs. time to close the ductus arteriosus or decrease the size of ductus). ? To evaluate the relationship between acetaminophen concentration and toxicity occurrence. Phase III: ? Early prophylactic treatment by acetaminophen decreases pain score and opiate consumption during the first 5 days of life. ? Early prophylactic treatment by acetaminophen reduces the number of back-up treatment of PDA (NSAIDs, surgery, trans-catheter procedure) ? Early prophylactic treatment by acetaminophen reduces catecholamines, opioid and parenteral nutrition requirements ? Pharmacokinetics of acetaminophen (in 50 preterms).;Primary end point(s): Primary endpoint of phase II is the closure of Ductus Arteriosus (DA) assessed by echocardiography during the first 7 days of life, defined as DA closed at two consecutive echocardiographies or if the DA is closed at echocardiography of Day 7 Primary endpoint of phase III is the survival without severe morbidity at 36 weeks of post menstrual age or at first discharge home, whichever comes first. The severe morbidities include bronchopulmonary dysplasia (BPD Grade 3 according to NIH consensus), necrotizing enterocolitis (NEC) of Bell's stage II or III, intraventricular hemorrhage (IVH) grade III-IV or cystic leukomalacia observed at a

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Secondary

Measure	Time frame
Secondary end point(s): Main secondary endpoints of phase II are tolerance of acetaminophen. We will investigate: (1) Acetaminophen serum levels (2) Serum ALAT & ASAT (3) Prospective clinical monitoring (4) Adverse effects and concomitant drug exposures Main secondary endpoints of phase III are: (1) Number of rescue treatment to close ductus by non steroid antiinflamatory drugs (NSAIDs) or by surgery or by transcatheter. (2) Diastolic systemic arterial pressure during the first week (3) Early and all Pulmonary hemorrhage (4) Cathecholamines, and opiate consumption during the first week of life (5) Volume of enteral nutrition during the first week of life (6) Interaction between parent involvement during the first week of life and medical care;Timepoint(s) of evaluation of this end point: At 36 weeks of post menstrual age or at first discharge home	—

Measure

Time frame

Secondary end point(s): Main secondary endpoints of phase II are tolerance of acetaminophen. We will investigate: (1) Acetaminophen serum levels (2) Serum ALAT & ASAT (3) Prospective clinical monitoring (4) Adverse effects and concomitant drug exposures Main secondary endpoints of phase III are: (1) Number of rescue treatment to close ductus by non steroid antiinflamatory drugs (NSAIDs) or by surgery or by transcatheter. (2) Diastolic systemic arterial pressure during the first week (3) Early and all Pulmonary hemorrhage (4) Cathecholamines, and opiate consumption during the first week of life (5) Volume of enteral nutrition during the first week of life (6) Interaction between parent involvement during the first week of life and medical care;Timepoint(s) of evaluation of this end point: At 36 weeks of post menstrual age or at first discharge home

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Countries

Austria, Belgium, Denmark, Estonia, Finland, France, Greece, Hungary, Ireland, Italy, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom

Contacts

Public ContactSandrine COUFFIN-CADIERGUES

Inserm

rqrc.siege@inserm.fr33144 23 64 16

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026