Combination of Acetaminophen and Ibuprofen in the Management of Patent Ductus Arteriosus

NCT03103022 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB201601912 - Jax
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Patent ductus arteriosus or PDA is a blood vessel that connects the right and left side of the heart that usually closes after birth but remains open in some premature infants born before 30 weeks' gestation. When this blood vessel remains open for a long time, it may cause problems such as bleeding in the lung and brain, lung injury due to prolonged need of ventilator, and poor kidney function. It sometimes becomes necessary to close this blood vessel in the preterm infant. Currently, this blood vessel can be closed either by medication or surgery. Pain medications such as Ibuprofen and Indomethacin are routinely used medications to close PDA. However, in the last 5 year, acetaminophen has been found as an alternative medication to close PDA in preterm infants. In multiple studies, acetaminophen is found to be a safe alternative medication with lower side effects than current standard management. Intravenous Ibuprofen is approved by FDA to treat PDA in preterm infants. Although not approved by FDA, oral ibuprofen is being used for the management of PDA. However, the success rate of a single medication is approximately 70%. Both medications have been used in the previous clinical studies to treat the same condition in the preterm infants and fewer side effects were reported. Mechanism of both medications to close PDA is different and may work more effectively together than single medication alone. In this study, the investigator are going to use these two medications (Ibuprofen and Acetaminophen) at the same time if the child needs treatment and is eligible to participate in this study. This study is based on the assumption that by using both medications at the same time, investigator can close this blood vessel more effectively than with either drug alone.

Conditions

Patent Ductus Arteriosus; Neonate

Outcome Measures

Primary Outcomes (1)

• Ductal closing rate

  To determine the ductal closure rate on echocardiography after completion of a first treatment course.

  within 24-48 hrs after completion of treatment.

Secondary Outcomes (11)

• Rate of ductal reopening

  From birth until discharge / 36 weeks post menstrual age

• Neonatal outcomes - Sepsis

  until discharge / 36 weeks post menstrual age

• Neonatal outcomes - Necrotizing Enterocolitis

  until discharge / 36 weeks post menstrual age

• Neonatal outcomes - Bronchopulmonary Dysplasia

  until discharge / 36 weeks post menstrual age

• neonatal outcomes - Ventilator days

  until discharge / 36 weeks post menstrual age

Study Arms (1)

Interventional Group

EXPERIMENTAL

Preterm infants who met the eligibility criteria will receive both oral acetaminophen and ibuprofen. Oral acetaminophen \[160 mg/5ml concentration\] will be administered every 6 hours with dose of 15 mg/kg/dose for a total of twelve doses and oral ibuprofen \[100 mg/5 ml\] at 10 mg/kg/dose on first day followed by 5 mg/kg/dose at 24 and 48 hours for a total of three doses

Drug: Acetaminophen; Drug: ibuprofen

Interventions

Acetaminophen DRUG

Oral acetaminophen \[160 mg/5ml concentration\] will be administered every 6 hours with dose of 15 mg/kg/dose for a total of twelve doses

Also known as: Tylenol

Interventional Group

ibuprofen DRUG

Oral ibuprofen \[100 mg/5 ml\] at 10 mg/kg/dose on first day followed by 5 mg/kg/dose at 24 and 48 hours for a total of three doses

Also known as: Motrin

Interventional Group

Eligibility Criteria

• Age: 23 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infant with gestational age 23 to 30 weeks at birth and birth weight between 500 - 1000 grams
• Postnatal age less than equal to 14 days
• Hemodynamically significant PDA as defined by any of the following:
• Increased ventilator support attributed by the clinician to be due to PDA
• Hypotension and/or widening pulse pressure requiring vasopressors
• Signs of congestive heart failure such as pulmonary congestion
• Echocardiographic criteria:
• Ratio of the smallest ductal diameter to the ostium of the left pulmonary artery \> 0.5

You may not qualify if:

• PDA-dependent congenital heart disease
• Prior treatment with prophylactic indomethacin
• Significant hyperbilirubinemia requiring exchange transfusion
• Active or suspected necrotizing enterocolitis (NEC) and/or intestinal perforation
• Abnormal liver enzymes
• Platelets count \< 50000 /l and / or active intracranial or gastrointestinal bleeding or from any other site
• Major congenital anomalies such as neural tube defect, chromosomal abnormality and gastrointestinal defect

Sponsors & Collaborators

• University of Florida: lead

Study Sites (2)

Wolfson Children's Hospital

Jacksonville, Florida, 32207, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (32)

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MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 6, 2017
• Study Start: June 12, 2017
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)