Addition of Acetaminophen in Standard PDA Management

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Patent Ductus Arteriosus

Intervention / Treatment
-----------------
* Drug: Intravenous Ibuprofen
* Drug: Intravenous Ibuprofen + Oral Acetaminophen


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Increased ventilator or oxygen support attributed by the clinician to be due to increased left-right shunting through the PDA 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) Signs of congestive heart failure (e.g increased pulmonary congestion on chest radiograph or hepatomegaly on physical examination) Echocardiographic criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 23 Weeks
Maximum Age: 28 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ibuprofen+Acetaminophen Group<br>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<br>* 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.<br>|
| Placebo Comparator: Ibuprofen Group<br>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<br>* The control monotherapy group will receive 10 mg/kg intravenous ibuprofen followed by 5 mg/kg 24 and 48 hours subsequently.<br>|

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 |