Randomized Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus

NCT03701074 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-081/730216-8
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the present study is to determine whether treatment of hemodynamically significant patent ductus arteriosus with a combined therapy of intravenous Ibuprofen and oral acetaminophen has higher success rate in closing the ductus arteriosus than a standard treatment strategy of using intravenous ibuprofen alone among preterm infants.

Conditions

Patent Ductus Arteriosus; Preterm Infant; Bronchopulmonary Dysplasia

Keywords

patent ductus arteriosus; acetaminophen; ibuprofen; bronchopulmonary dysplasia; mechanical ventilation

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Ductus Arteriosus Closure/Constriction

  Ductal closure/constriction rate as defined based on the echocardiographic findings. Ductal closure/constriction will be defined as the complete closure of ductus or ductal diameter \<1 mm

  24-48 hours after the completion of study intervention

Secondary Outcomes (22)

• Echocardiographic Patent Ductus Arteriosus Parameters Before and After the Study Intervention

  24-48 hours after the completion of study intervention

• Ventilatory Settings Before and After the Study Intervention

  24-48 hours after the completion of study intervention

• Proportion of Participants With Liver Injury

  24-48 hours after the completion of study intervention

• Proportion of Participants With Renal Injury

  24-48 hours after the completion of study intervention

• Proportion of Participants With Hematological Adverse Events

  24-48 hours after the completion of study intervention

Study Arms (2)

ibuprofen and acetaminophen arm (intervention arm)

EXPERIMENTAL

ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Acetaminophen will be administered as oral formulation. Acetaminophen is given at a dose of 15 mg/Kg/dose, q 6 hours, for 3 days (total of 12 doses).

Drug: Ibuprofen and acetaminophen

ibuprofen and placebo arm (control arm)

ACTIVE COMPARATOR

ibuprofen and acetaminophen will be administered concomitantly. Ibuprofen will be administered through intravenous route. The dose of ibuprofen will be the standard dosing regimen used in our unit: dosing based on the postnatal age. For Infants \> 108 h of postnatal age: 18 mg/kg/dose loading dose followed by 9 mg/kg/dose, two doses at q24 intervals, started 24 h after the loading dose. Placebo will be sterile water, with similar volume and color as acetaminophen, will be given through the oro-gastric tube, for three days at 6 h intervals.

Drug: Ibuprofen and placebo

Interventions

Ibuprofen and acetaminophen DRUG

Intravenous ibuprofen given concomitantly with oral acetaminophen

ibuprofen and acetaminophen arm (intervention arm)

Ibuprofen and placebo DRUG

Intravenous ibuprofen given concomitantly with oral placebo

ibuprofen and placebo arm (control arm)

Eligibility Criteria

• Age: 5 Days - 21 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infant ≤27 6/7
• Written parental consent is obtained
• Infant requires respiratory support
• diagnosis of a persistent patent ductus arteriosus after 5 days of age, (defined as at least two of the following:
• Ductus size ≥ 1.5 mm
• Maximum flow velocity through the ductus ≤ 2 m/s
• Left atrium to aorta ratio ≥ 1.4
• Wide pulse pressure
• B-type natriuretic peptide (BNP)
• Attending neonatologist made decision to treat patent ductus arteriosus

You may not qualify if:

• No parental consent
• Infants \> 21days of postnatal age
• Congenital anomalies such as cardiac or multiple anomalies
• Infection (e.g., septicemia, pneumonia)
• Bleeding disorder or platelet count\< 50,000/ml
• Acute kidney injury (AKI)defined as oliguria (urine output\< 0.5 ml/kg/hr for 16hrs) and/or serum creatinine \> 1.5 mg/dl
• Elevated liver enzymes (\>2 fold from upper normal limits)
• Pulmonary hypertension or right to left shunt through the ductus arteriosus
• Diagnosis of necrotizing enterocolitis
• Unable to tolerate oral medications at the time of enrollment.

Sponsors & Collaborators

• University of South Alabama: lead

Study Sites (1)

University of South Alabama

Mobile, Alabama, 36607, United States

Location

MeSH Terms

Conditions

Ductus Arteriosus, Patent; Premature Birth; Bronchopulmonary Dysplasia

Interventions

Ibuprofen; Acetaminophen

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Results Point of Contact

• Title: Ramachandra Bhat
• Organization: University of South Alabama

rambhat79@gmail.com

2514151055

Study Officials

• Fabien Eyal, MD

  University of South Alabama

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: October 9, 2018
• Study Start: December 15, 2018
• Primary Completion: October 30, 2020
• Study Completion: December 2, 2020
• Last Updated: April 30, 2026
• Results First Posted: May 11, 2021

Record last verified: 2026-04

Locations

US (1)