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

NCT ID: NCT03701074

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-15
• Study Completion Date: 2020-12-02

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.

Detailed Description

The primary objectives of the study are to confirm the safety of oral acetaminophen in extremely low birth infants, given concomitantly with intravenous ibuprofen and also to determine its efficacy in significantly increasing the rates of ductal closure when compared to only intravenous ibuprofen therapy. Hence primary outcome variable include patent ductus arteriosus closure success rate, based on the 2-D transthoracic echocardiographic evidence.

This study is a single center, randomized, double blinded, placebo controlled trial. Preterm infants with gestational age of with a gestational age ≤27 6/7 weeks by the best obstetric estimate are eligible for enrollment.

For randomization, the study population will be stratified to two subgroups based on gestational age (GA ≤24 weeks and > 25 weeks). Randomization will occur by using computer generated random sequence, using a 4-block design, with 1:1 parallel allocation. Allocations include treatment and control arm. Treatment arm will receive combination of intravenous ibuprofen and oral acetaminophen, while control arm will receive intravenous Ibuprofen and oral placebo.

Conditions

Patent Ductus Arteriosus; Preterm Infant; Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ibuprofen and acetaminophen arm (intervention arm)

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).

Group Type: EXPERIMENTAL

Ibuprofen and acetaminophen

Intervention Type: DRUG

Intravenous ibuprofen given concomitantly with oral acetaminophen

ibuprofen and placebo arm (control arm)

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.

Group Type: ACTIVE_COMPARATOR

Ibuprofen and placebo

Intervention Type: DRUG

Intravenous ibuprofen given concomitantly with oral placebo

Interventions

Ibuprofen and acetaminophen

Intravenous ibuprofen given concomitantly with oral acetaminophen

Intervention Type: DRUG

Ibuprofen and placebo

Intravenous ibuprofen given concomitantly with oral placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Preterm infant ≤27 6/7

2. Written parental consent is obtained

3. Infant requires respiratory support

4. diagnosis of a persistent patent ductus arteriosus after 5 days of age, (defined as at least two of the following:

1. Ductus size ≥ 1.5 mm

2. Maximum flow velocity through the ductus ≤ 2 m/s

3. Left atrium to aorta ratio ≥ 1.4

4. Wide pulse pressure

5. B-type natriuretic peptide (BNP)

5. Attending neonatologist made decision to treat patent ductus arteriosus

Exclusion Criteria

1. No parental consent

2. Infants > 21days of postnatal age

3. Congenital anomalies such as cardiac or multiple anomalies

4. Infection (e.g., septicemia, pneumonia)

5. Bleeding disorder or platelet count< 50,000/ml

6. Acute kidney injury (AKI)defined as oliguria (urine output< 0.5 ml/kg/hr for 16hrs) and/or serum creatinine > 1.5 mg/dl

7. Elevated liver enzymes (>2 fold from upper normal limits)

8. Pulmonary hypertension or right to left shunt through the ductus arteriosus

9. Diagnosis of necrotizing enterocolitis

10. Unable to tolerate oral medications at the time of enrollment.

• Minimum Eligible Age: 5 Days
• Maximum Eligible Age: 21 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of South Alabama

OTHER

Sponsor Role: lead

Responsible Party

Ramachandra Bhat

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fabien Eyal, MD

Role: STUDY_DIRECTOR

University of South Alabama

Locations

University of South Alabama

Mobile, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15-081/730216-8

Identifier Type: -

Identifier Source: org_study_id