Acetaminophen vs Indomethacin in Treating hsPDA

November 27, 2019 updated by: University of Tennessee

Comparison of the Efficacy of IV Acetaminophen Versus IV Indomethacin in Treatment of Hemodynamically Significant PDA in VLBW Infants

The purpose of this study is to see if acetaminophen (Tylenol) is as effective as indomethacin in closing patent ductus arteriosus in premature infants.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The study will be a randomized, controlled, non-inferiority trial, and the investigators plan to enroll premature infants <32 weeks, <1500g, and who are < 21 days of age at Regional One Health, LeBonheur Children's Hospital, and Methodist Germantown NICUs in Memphis, TN. A study group of 42 patients for each group will be needed to allow a maximum difference of 25% to consider non-inferiority in the closure rate between IV acetaminophen and IV indomethacin (with power of 80% and alpha of 0.05).2 The investigators' goal will be to enroll 50 infants for each treatment group, to help with an expected 20% drop out rate either due to complications or parents removal of consent. Dosages: IV acetaminophen 15mg/kg/dose every 6 hours for 12 doses,6 IV indomethacin dose will depend on age.IV indomethacin will be given every 12 hours for 3 doses. The infants will be eligible for the study after primary attending has made the decision to treat the hsPDA. The goal will be 50 infants in the IV acetaminophen group and 50 infants in the IV indomethacin group.

Informed consent will be obtained from the parent after ECHO has been obtained and the primary attending has decided to treat PDA in the infant who meets inclusion criteria without any of the exclusion criteria. The investigators will use block randomization and stratify by site to generate 140 random values of either 0 for acetaminophen or 1 for indomethacin. The goal will be 50 infants randomized to acetaminophen group and 50 infants randomized to indomethacin group. The numbers will be placed in opaque envelope and opened after consent is obtained. The primary team will not be blinded given the different frequencies of administration of acetaminophen and indomethacin. The first ECHO will be read by staff pediatric cardiologist. A pediatric cardiologist will retrospectively go back and read all ECHOs blinded for standardization.

Prior to induction of treatment, we will record complete blood count (CBC) and complete metabolic panel (CMP) with AST/ALT. After treatment, the investigators will record AST/ALT within 48 hours, and will record follow-up ECHO reports that occur within seven days of initiation of treatment. The decision to repeat treatment will be left to primary attending's discretion. The primary attending will determine any additional medical or surgical treatment if indicated. Data regarding ROP, IVH, and BPD will be collected from patient's chart prior to discharge.

Primary outcome will be the rate of successful PDA treatment by ECHO in each group. Successful PDA treatment will be defined as no longer meeting ECHO criteria for hsPDA. Secondary outcome data will be recorded and include the following: retreatment, surgical closure, days on invasive mechanical ventilation, duration of supplemental oxygen requirement, respiratory support at 36 weeks post-menstrual age (PMA), NEC, ROP, days to full feeds, gastrointestinal perforation, length of stay, renal dysfunction defined by UOP < 1cc/kg/hr in an 8 hour period, creatinine elevation greater than 1.5 mg/dL, and discharge disposition.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38103
        • LeBonheur Children's Hospital
      • Memphis, Tennessee, United States, 38138
        • Methodist-Lebonheur Germantown Hospital
      • Memphis, Tennessee, United States, 38163
        • Regional One Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 7 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Gestational age at birth 22 weeks to 31 6/7 weeks.
  • Birth weight ≤ 1500 grams
  • Day of life ≤ 21 days
  • ECHO findings:

Left-to-right ductal flow AND 2 of the following 3:

  • Ductal size > 1.5mm at smallest diameter
  • Reversal of flow in descending aorta
  • Left atrial size to aortic root ratio >1.5
  • Platelet count > 50,000

Exclusion Criteria:

  • Ductal dependent congenital heart disease
  • Major congenital anomaly
  • Life-threatening infection
  • Urine output < 1cc/kg/hr in prior 8 hours
  • Serum creatinine > 1.8 mg/dL
  • Hyperbilirubinemia requiring exchange transfusion
  • Active NEC Stage 2 or 3 using Bell's staging criteria
  • Active intestinal perforation
  • Liver dysfunction [2x upper limit of normal for aspartate aminotransferase(AST) and/or alanine aminotransferase (ALT)]
  • Active GI bleeding
  • Concurrent hydrocortisone use
  • Known IVH Grade 3 or 4

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Indomethacin
Indomethacin as drug to treat PDA.
Drug: Indomethacin
IV indomethacin will be given every 12 hours for 3 doses. If <48 hours old, 1st dose 0.2 mg/kg, 2nd dose 0.1 mg/kg, and 3rd dose 0.1mg/kg. If 2-7 days old, 1st dose 0.2 mg/kg, 2nd dose 0.2 mg/kg, and 3rd dose 0.2 mg/kg. If >7 days old, 1st dose 0.2 mg/kg, 2nd dose 0.25 mg/kg, and 3rd dose 0.25 mg/kg.
Other Names:
  • Indocin
Experimental: Acetaminophen
Acetaminophen as drug to treat PDA.
Drug: Acetaminophen
15mg/kg/dose every 6 hours for 12 doses
Other Names:
  • Ofirmev

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Successful treatment of PDA closure
Time Frame: Follow-up ECHO to assess for closure within 7 days of treatment initiation
Definition of successful treatment of PDA is the PDA no longer meets the echocardiogram inclusion criteria.
Follow-up ECHO to assess for closure within 7 days of treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PDA retreatment
Time Frame: 1 year
Did the patient require a second course of treatment with either indomethacin or acetaminophen. Did the PDA require surgical closure.
1 year
Supplement O2 requirement at 36 weeks PMA
Time Frame: Until 36 weeks PMA
Was infant on >21% O2 at 36 weeks post-menstrual age
Until 36 weeks PMA
Nectrotizing enterocolitis
Time Frame: 1 year
As defined by Bell's Staging criteria, at any time during hospital stay
1 year
Gastrointestinal perforation
Time Frame: 1 year
As defined by xray demonstration of free peritoneal air or as diagnosed by surgery
1 year
Mortality
Time Frame: 1 year
Death before discharge from NICU stay
1 year
Days on invasive mechanical ventilation
Time Frame: 1 year
Days on invasive mechanical ventilation
1 year
Days on supplement oxygen
Time Frame: 1 year
Days on supplement oxygen
1 year
Days to full feeds
Time Frame: 1 year
Day till the infant reaches 120 kcal/kg/d
1 year
Length of stay
Time Frame: 1 year
Time from NICU admission to NICU discharge
1 year
Retinopathy of prematurity
Time Frame: 1 year
Stage of ROP and if any treatment was needed
1 year
Creatinine elevation greater than 1.5 mg/dL
Time Frame: 1 year
Creatinine elevation greater than 1.5 mg/dL
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Tennessee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2016

Primary Completion (Actual)

September 1, 2018

Study Completion (Actual)

September 1, 2018

Study Registration Dates

First Submitted

April 30, 2018

First Submitted That Met QC Criteria

May 23, 2018

First Posted (Actual)

May 25, 2018

Study Record Updates

Last Update Posted (Actual)

December 3, 2019

Last Update Submitted That Met QC Criteria

November 27, 2019

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-04411-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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