Clinical trial NCT03537144: Acetaminophen vs Indomethacin in Treating hsPDA
Official title: Comparison of the Efficacy of IV Acetaminophen Versus IV Indomethacin in Treatment of Hemodynamically Significant PDA in VLBW Infants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Patent Ductus Arteriosus
Keywords: Patent ductus arteriosus
acetaminophen
indomethacin
Lead sponsor: University of Tennessee
Sponsor class: OTHER
First posted: 2018-05-25
Enrollment: 37
Sex: ALL
Minimum age (years): 22
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Successful treatment of PDA closure
timeFrame: Follow-up ECHO to assess for closure within 7 days of treatment initiation
Secondary outcomes:
measure: PDA retreatment
timeFrame: 1 year
measure: Supplement O2 requirement at 36 weeks PMA
timeFrame: Until 36 weeks PMA
measure: Nectrotizing enterocolitis
timeFrame: 1 year
measure: Gastrointestinal perforation
timeFrame: 1 year
measure: Mortality
timeFrame: 1 year
measure: Days on invasive mechanical ventilation
timeFrame: 1 year
measure: Days on supplement oxygen
timeFrame: 1 year
measure: Days to full feeds
timeFrame: 1 year
measure: Length of stay
timeFrame: 1 year
measure: Retinopathy of prematurity
timeFrame: 1 year
measure: Creatinine elevation greater than 1.5 mg/dL
timeFrame: 1 year
Other outcomes:
Locations:
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: Methodist-Lebonheur Germantown Hospital
state: Tennessee
city: Memphis
country: United States
facility: Regional One Health
state: Tennessee
Study officials:
References:
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