Efficacy and safety of paracetamol in the treatment of patent ductus arteriosus in preterm infants.

Phase 1

• Conditions: Patent ductus arteriosus; MedDRA version: 16.1Level: LLTClassification code 10034190Term: PDA Repair patent ductus arteriosusSystem Organ Class: 100000004865; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2013-003883-30-IT
• Lead Sponsor: Aziende Chimiche Riunite Angelini Francesco ACRAF S.p.A

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-11-12
• Study Completion: 2019-04-17
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

Male or female preterm infants with no limitation of race.
Gestational age 25+0-31+6 weeks.
Age 24-72 hours.
Echocardiographic evidence of hemodynamically significant patent ductus arteriosus at the first 24-72 hours of life.
The diagnosis of hemodynamically significant PDA requiring treatment will be made by echocardiographic demonstration of a ductal left-to-right shunt, with a left atrium-to-aortic root ratio >1.3 or a ductal size >1.5 mm and excluding the cases in which the closing flow pattern suggests a restrictive PDA [Varvarigou 1996, Su 2008].
Willingness of the parents/legally authorized representative/child to sign the Informed Consent Form.

Are the trial subjects under 18? yes
Number of subjects for this age range: 110
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Outborn patients.
Major congenital anomalies, including but not limited to congenital heart defects, Down syndrome newborn and/or newborn suffering from congenital anomalies diagnosed during the fetal period.
Known positive HIV and/or known positive HCV newborn’s mother.
Life threatening infection, complicated or not by multiple organ dysfunction and failure syndrome.
Hydrops fetalis.
Pulmonary hypertension diagnosed in the first 24-48 hours of life by means of heart ultrasound when the presence of a right-to-left shunt through the foramen ovale or ductus arteriosus is demonstrated, or when the estimated pulmonary pressure, in terms of the tricuspid regurgitation jet, is greater than two-thirds of the systemic arterial pressure.
Grade 3 or 4 intraventricular haemorrhage (IVH).
Urine output <1 ml/kg of body weight/h during a 24 h collection period or urine output <0.5 ml/kg of body weight/h in case it is measured at 24 hours of life of newborn.
Serum creatinine concentration > 1.5 mg/dl (132 µmol/l).
Platelet count < 50,000/mm3.
Major bleeding, as revealed by haematuria, or blood in the endotracheal aspirate, gastric aspirate, or stools, or consistent oozing of blood from puncture sites.
Severe liver failure, defined as elevated liver enzymes (ALT/GPT and AST/GOT) > 2 times the upper boundary of the normal range. For this kind of population the following normal ranges will be considered [Rosenthal, 1997]:
- ALT/GPT: 6-50 U/L
- AST/GOT: 35-140 U/L
Medical need of administering other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) different from ibubrofen.
Participation to another trial involving any investigational drug.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The study objective is to assess the efficacy and safety of paracetamol in comparison to ibuprofen in the treatment of patent ductus arteriosus in preterm infants.;Secondary Objective: Not applicable;Primary end point(s): Primary end-point: <br>success rate in closing PDA using paracetamol in comparison to ibuprofen after the first 3 days of treatment. <br>;Timepoint(s) of evaluation of this end point: Day 3 (visit 3)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints: <br>•number of re-openings at 30 days; <br>•success rate in closing PDA after the second treatment course of ibuprofen as rescue medication; <br>•success rate of closing PDA after the first day and the second day of the first treatment course;<br>•incidence of surgical ligation at 30 days;<br>•incidence of renal failure, liver failure, gastrointestinal complications (including isolated intestinal perforation) at 30 days;<br>•incidence of death at 30 days and at 40 weeks post-conception;<br>•incidence of sepsis at 30 days; <br>•hospital-stay duration in Neonatal Intensive Care Unit;<br>•occurrence of adverse events at 30 days. <br>;Timepoint(s) of evaluation of this end point: Day 30 (followup 3) or 40 weeks post-conception (follow-up 4)