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

Bronchopulmonary Dysplasia Clinical Trial

Official title:

Single Center, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of Acetaminophen in Preterm Infants Used in Combination With Ibuprofen for Closure of the Ductus Arteriosus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03701074
• Other study ID #: 15-081/730216-8
• Status: Terminated
• Phase: Phase 2
• Start date: December 15, 2018
• Est. completion date: December 2, 2020

Study information

• Verified date: April 2021
• Source: University of South Alabama
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 2, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Days

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Ductus Arteriosus, Patent
• Patent Ductus Arteriosus
• Premature Birth
• Preterm Infant

Intervention

Drug:
• Ibuprofen and acetaminophen
Intravenous ibuprofen given concomitantly with oral acetaminophen
• Ibuprofen and placebo
Intravenous ibuprofen given concomitantly with oral placebo

Locations

Country	Name	City	State
United States	University of South Alabama	Mobile	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of South Alabama

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ductus Arteriosus Closure/Constriction Rate	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	Echocardiographic Patent Ductus Arteriosus Parameters Before and After the Study Intervention		24-48 hours after the completion of study intervention
Secondary	Ventilatory Settings Before and After the Study Intervention		24-48 hours after the completion of study intervention
Secondary	Rate of Liver Injury	liver enzymes before and after the study intervention	24-48 hours after the completion of study intervention
Secondary	Rate of Renal Injury	Blood urea nitrogen (BUN) and serum creatinine before and after the study intervention	24-48 hours after the completion of study intervention
Secondary	Rate of Hematological Adverse Events	Hematocrit and platelets before and after the study intervention	24-48 hours after the completion of study intervention
Secondary	Total Number of Days of Mechanical Ventilation		from randomization until discharge/40 weeks post menstrual age
Secondary	Total Number of Days of Need for Supplemental Oxygen		from randomization until discharge/40 weeks post menstrual age
Secondary	Duration of Noninvasive Ventilation		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Persistence of Ductus-needing Pharmacological Treatment		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Surgical Ligation of PDA		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Bronchopulmonary Dysplasia		at 36 weeks post menstrual age
Secondary	Percentage of Infants Requiring Home Oxygen Therapy		at discharge/40 weeks post menstrual age
Secondary	Death Before Discharge		until discharge/40 weeks post menstrual age
Secondary	Time to Achieve Full Enteral Feeding	Time to achieve 120 ml/kg/day of enteral feeding	from birth until discharge/40 weeks post menstrual age
Secondary	Days on Total Parenteral Nutrition		from birth until discharge/40 weeks post menstrual age
Secondary	Retinopathy of Prematurity		from birth until discharge/40 weeks post menstrual age
Secondary	Rate of Spontaneous Intestinal Perforation		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Necrotizing Enterocolitis		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Gastrointestinal Hemorrhage		from randomization until discharge/40 weeks post menstrual age
Secondary	Rate of Late Onset Sepsis		from randomization until discharge/40 weeks post menstrual age
Secondary	Length of Hospital Stay		from birth until discharge/40 weeks post menstrual age
Secondary	Rate of Periventricular Leukomalacia		from randomization until discharge/40 weeks post menstrual age