Prophylactic Treatment of the Ductus Arteriosus in Preterm Infants by Acetaminophen

Summary

TREOCAPA is a Phase II/III European Multicentre study concerning the prophylactic treatment by Acetaminophen of extremely preterm infant during the first five days after birth. The Phase II is a dose finding phase in order to assess the minimum effective dose regimen of acetaminophen for the closure of PDA for neonates with a gestational age less than 27 weeks This part of the study will be conducted in 11 NICUs, in 4 countries (France, UK, Finland and Denmark). The Phase III is The phase III is a randomized, multicenter, double-blind, placebo-controlled superiority trial, two arms in a 1:1 ratio, evaluating an increasing of 10% of the percentage of survival without severe morbidity at 36 weeks of post menstrual age. In the intervention arm, 20 mg/kg followed by 7.5 mg/kg quarter in die (QID) will be administered to the 27-28 weeks gestational age group (dosage confirmed through PK/PD data analysis from the previous Finnian study) and the dosage selected after the conclusion of the Phase II will be administered to the 23-26 weeks gestational age group. A group sequential design, with a total of 3 analyses (2 interim analyses and a final) and the O'Brien-Fleming alpha spending function is chosen for the trial. At the same time, a Bayesian sequential analysis is planned for safety endpoints

Timeline

Start

2020-10-29

Primary completion

2024-06-20

Completion

2024-06-20

Publications

• Results Padavia F, Treluyer JM, Cambonie G, Flamant C, Rideau A, Tauzin M, Patkai J, Gascoin G, Lumia M, Aikio O, Foissac F, Urien S, Benaboud S, Lui G, Froelicher Bournaud L, Zheng Y, Kemper R, Tortigue M, Baruteau AE, Kallio J, Hallman M, Diallo A, Levoyer L, Roze JC, Bouazza N. Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis. Clin Pharmacokinet. 2025 Nov;64(11):1681-1691. doi: 10.1007/s40262-025-01567-4. Epub 2025 Sep 1.
• Results Ursino M, Alberti C, Cambonie G, Kemp R, Vanhecke A, Levoyer L, Diallo A, Hallman M, Roze JC; TREOCAPA study group. TREOCAPA: prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen-statistical analysis plan for the randomized phase III group sequential trial. Trials. 2025 Feb 13;26(1):52. doi: 10.1186/s13063-025-08751-8.
• Results Bouazza N, Cambonie G, Flamant C, Rideau A, Tauzin M, Patkai J, Gascoin G, Lumia M, Aikio O, Lui G, Bournaud LF, Walsh-Papageorgiou A, Tortigue M, Baruteau AE, Kallio J, Hallman M, Diallo A, Levoyer L, Treluyer JM, Roze JC. Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach. Paediatr Drugs. 2024 Jan;26(1):83-93. doi: 10.1007/s40272-023-00602-w. Epub 2023 Nov 17.
• Results Padavia F, Treluyer JM, Cambonie G, Flamant C, Rideau A, Tauzin M, Patkai J, Gascoin G, Lumia M, Aikio O, Foissac F, Urien S, Benaboud S, Lui G, Froelicher Bournaud L, Zheng Y, Kemper R, Tortigue M, Baruteau AE, Kallio J, Hallman M, Diallo A, Levoyer L, Roze JC, Bouazza N. Population Pharmacokinetics of Intravenous Paracetamol and Its Metabolites in Extreme Preterm Neonates in the Context of Patent Ductus Arteriosus Treatment. Clin Pharmacokinet. 2024 Dec;63(12):1689-1700. doi: 10.1007/s40262-024-01439-3. Epub 2024 Nov 22.
• Results Wan M, Turner MA, Cambonie G, Kemper R, Bouafia N, Levoyer L, Diallo A, Hallman M, Roze JC. Experience and lessons learned relating to investigational product supply in the design and delivery of a paediatric investigator-initiated clinical trial. Contemp Clin Trials Commun. 2025 Jun 30;46:101517. doi: 10.1016/j.conctc.2025.101517. eCollection 2025 Aug.
• Roze JC, Cambonie G, Flamant C, Patkai J, Muhlbacher T, Gascoin G, Rideau Batista Novais A, Tauzin M, Le Duc K, Beuchee A, Joye S, Babacheva E, Bouissou A, Ligi I, Tammela O, Plourde M, Dempsey E, Tosello B, Nguyen K, Vincent M, Andresson P, Binder C, Kruse C, Barcos Munoz F, Kuhn P, Proenca E, Bartocci M, Kermorvant-Duchemin E, Nellis G, Lumia M, Giapros V, Rigo V, Sankilampi U, Mendes da Graca A, Ronnestad A, Soukka H, Mondi V, Aikio O, Torre-Monmany N, Ruegger C, Baud O, Zeitlin J, Morgan AS, Baruteau AE, Ancel PY, Carbajal R, Bouazza N, Diallo A, Levoyer L, Kemper R, Hallman M, Alberti C, Ursino M; TREOCAPA Study Group. Prophylactic Treatment of Patent Ductus Arteriosus With Acetaminophen: A Randomized Clinical Trial. JAMA Pediatr. 2026 Apr 1;180(4):374-383. doi: 10.1001/jamapediatrics.2025.6150.

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