Addition of Acetaminophen in Standard PDA Management

Monotherapy (Ibuprofen) vs. Combination Therapy (Ibuprofen and Acetaminophen) in the Management of Patent Ductus Arteriosus in Premature Infants: A Randomized Controlled Trial

Patent ductus arteriosus is a common morbidity in preterm infants and management of PDA varies among neonatologist. The investigators are conducting a randomized controlled trial to determine the rates of initial patent ductus arteriosus (PDA) closure after completion of a first treatment course.

Study Overview

• Status: Withdrawn
• Conditions: Patent Ductus Arteriosus
• Intervention / Treatment: Drug: Intravenous Ibuprofen + Oral Acetaminophen; Drug: Intravenous Ibuprofen

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants 23 0/7 to 27 6/7 weeks' gestational age and birth weight < 1000 grams

• Hemodynamically significant PDA as defined by any of the following:

  1. Increased ventilator or oxygen support attributed by the clinician to be due to increased left-right shunting through the PDA
  2. Hypotension and/or widening pulse pressure requiring continuous dopamine infusion (hypotension is defined as mean arterial pressure (MAP) at least 2-3 mmHg below the infants' post menstrual age)
  3. Signs of congestive heart failure (e.g increased pulmonary congestion on chest radiograph or hepatomegaly on physical examination)

• Echocardiographic criteria:

  1. Ratio of the smallest ductal diameter to the ostium of the left pulmonary artery > 0.5

Exclusion Criteria:

• No enteral feedings
• PDA-dependent congenital heart disease
• Prior treatment with prophylactic indomethacin
• Prior PDA treatment with any medications
• Suspected or diagnosed acute necrotizing enterocolitis (NEC) or spontaneous intestinal perforation
• Abnormal liver enzymes (ALT > 60 IU/L and AST > 60 IU/L)
• Platelets count < 50,000 /μl; and / or active intracranial, gastrointestinal, or other bleeding
• Major congenital anomalies such as neural tube defect, known or suspected chromosomal abnormality, and gastrointestinal defect
• Prior enrollment to other interventional clinical study where PDA is an outcome variable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Ibuprofen+Acetaminophen Group; Infants with PDA randomized to the combined treatment group receiving intravenous ibuprofen (10 mg/kg intravenous ibuprofen followed by 5 mg/kg 24 and 48 hours subsequently) and oral acetaminophen (15 mg/kg oral acetaminophen [160 mg/5ml concentration] every 6 hours for a total of 12 doses).	Drug: Intravenous Ibuprofen + Oral Acetaminophen; The combined treatment group will receive 10 mg/kg intravenous ibuprofen followed by 5 mg/kg 24 and 48 hours subsequently and will in addition receive 15 mg/kg oral acetaminophen [160 mg/5ml concentration] every 6 hours for a total of 12 doses.
PLACEBO_COMPARATOR: Ibuprofen Group; Infants with PDA randomized to the control mono therapy group receiving intravenous ibuprofen (10 mg/kg intravenous ibuprofen followed by 5 mg/kg 24 and 48 hours subsequently) alone.	Drug: Intravenous Ibuprofen; The control monotherapy group will receive 10 mg/kg intravenous ibuprofen followed by 5 mg/kg 24 and 48 hours subsequently.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of infants with PDA closure.	Percentage of patients who demonstrated PDA closure.	During hospitalization, up to 10 days

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Sanket D Shah, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2021
• Primary Completion (ACTUAL): May 12, 2021
• Study Completion (ACTUAL): May 12, 2021

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: July 18, 2019
• First Posted (ACTUAL): July 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Ductus Arteriosus, Patent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: IRB201901829 -A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No