NCT03537144

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jun 2016

Geographic Reach
1 country

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2016

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

April 30, 2018

Completed
25 days until next milestone

First Posted

Study publicly available on registry

May 25, 2018

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2018

Completed
Last Updated

December 3, 2019

Status Verified

May 1, 2018

Enrollment Period

2.3 years

First QC Date

April 30, 2018

Last Update Submit

November 27, 2019

Conditions

Patent Ductus Arteriosus

Keywords

Patent ductus arteriosusacetaminophenindomethacin

Outcome Measures

Primary Outcomes (1)

  • Successful treatment of PDA closure

    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 Outcomes (11)

  • PDA retreatment

    1 year

  • Supplement O2 requirement at 36 weeks PMA

    Until 36 weeks PMA

  • Nectrotizing enterocolitis

    1 year

  • Gastrointestinal perforation

    1 year

  • Mortality

    1 year

  • +6 more secondary outcomes

Study Arms (2)

Indomethacin

ACTIVE COMPARATOR

Indomethacin as drug to treat PDA.

Drug: Indomethacin

Acetaminophen

EXPERIMENTAL

Acetaminophen as drug to treat PDA.

Drug: Acetaminophen

Interventions

IndomethacinDRUG

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.

Also known as: Indocin
Indomethacin
AcetaminophenDRUG

15mg/kg/dose every 6 hours for 12 doses

Also known as: Ofirmev
Acetaminophen

Eligibility Criteria

Age22 Weeks - 32 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

LeBonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Methodist-Lebonheur Germantown Hospital

Memphis, Tennessee, 38138, United States

Location

Regional One Health

Memphis, Tennessee, 38163, United States

Location

Related Publications (18)

  • Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011 Dec;128(6):e1618-21. doi: 10.1542/peds.2011-0359. Epub 2011 Nov 7.

    PMID: 22065264RESULT

  • Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One. 2013 Nov 4;8(11):e77888. doi: 10.1371/journal.pone.0077888. eCollection 2013.

    PMID: 24223740RESULT

  • Nadir E, Kassem E, Foldi S, Hochberg A, Feldman M. Paracetamol treatment of patent ductus arteriosus in preterm infants. J Perinatol. 2014 Oct;34(10):748-9. doi: 10.1038/jp.2014.96. Epub 2014 May 22.

    PMID: 24854626RESULT

  • Jain A, Shah PS. Diagnosis, Evaluation, and Management of Patent Ductus Arteriosus in Preterm Neonates. JAMA Pediatr. 2015 Sep;169(9):863-72. doi: 10.1001/jamapediatrics.2015.0987.

    PMID: 26168357RESULT

  • Oncel MY, Yurttutan S, Degirmencioglu H, Uras N, Altug N, Erdeve O, Dilmen U. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2013;103(3):166-9. doi: 10.1159/000345337. Epub 2012 Dec 19.

    PMID: 23258386RESULT

  • EL-Khuffash A, James AT, Cleary A, Semberova J, Franklin O, Miletin J. Late medical therapy of patent ductus arteriosus using intravenous paracetamol. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F253-6. doi: 10.1136/archdischild-2014-307930. Epub 2015 Feb 4.

    PMID: 25653299RESULT

  • Gokmen T, Erdeve O, Altug N, Oguz SS, Uras N, Dilmen U. Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr. 2011 Apr;158(4):549-554.e1. doi: 10.1016/j.jpeds.2010.10.008. Epub 2010 Nov 20.

    PMID: 21094951RESULT

  • Evans N, Malcolm G, Osborn D, Kluckow M. Diagnosis of patent ductus arteriosus in preterm infants. Neonatal Rev 2004; 5: e86-e97.

    RESULT

  • Silverman NH, Lewis AB, Heymann MA, Rudolph AM. Echocardiographic assessment of ductus arteriosus shunt in premature infants. Circulation. 1974 Oct;50(4):821-5. doi: 10.1161/01.cir.50.4.821. No abstract available.

    PMID: 4418268RESULT

  • Ellison RC, Peckham GJ, Lang P, Talner NS, Lerer TJ, Lin L, Dooley KJ, Nadas AS. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics. 1983 Mar;71(3):364-72.

    PMID: 6338474RESULT

  • Dash SK, Kabra NS, Avasthi BS, Sharma SR, Padhi P, Ahmed J. Enteral paracetamol or Intravenous Indomethacin for Closure of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial. Indian Pediatr. 2015 Jul;52(7):573-8. doi: 10.1007/s13312-015-0677-z.

    PMID: 26244949RESULT

  • Thomson Reuters. Neofax 2011. Montvale, NJ: Thomson Reuters; 2011.

    RESULT

  • Martin, R. J., Fanaroff, A. A., & Walsh, M. C. (2015). Fanaroff and Martin's neonatal-perinatal medicine: Diseases of the fetus and infant (10th ed.). St. Louis, Mo.: Mosby/Elsevier

    RESULT

  • Clyman, R. Patent Ductus Arteriosus in the Preterm Infant. in: C.A. Gleason, SU Devaskar (Eds.) Avery's disease of the newborn.9th ed.WB Saunders, Philadelphia;2012:751-761.

    RESULT

  • Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, Sinha R, Erdeve O, Tekgunduz KS, Dogan M, Kessel I, Hammerman C, Nadir E, Yurttutan S, Jasani B, Alan S, Manguso F, De Curtis M. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2016 Mar;101(2):F127-36. doi: 10.1136/archdischild-2014-307312. Epub 2015 Aug 17.

    PMID: 26283668RESULT

  • Palmer GM, Atkins M, Anderson BJ, Smith KR, Culnane TJ, McNally CM, Perkins EJ, Chalkiadis GA, Hunt RW. I.V. acetaminophen pharmacokinetics in neonates after multiple doses. Br J Anaesth. 2008 Oct;101(4):523-30. doi: 10.1093/bja/aen208. Epub 2008 Jul 15.

    PMID: 18628265RESULT

  • Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15.

    PMID: 26672023RESULT

  • Gersony WM, Peckham GJ, Ellison RC, Miettinen OS, Nadas AS. Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study. J Pediatr. 1983 Jun;102(6):895-906. doi: 10.1016/s0022-3476(83)80022-5.

    PMID: 6343572RESULT

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

IndomethacinAcetaminophen

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

IndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAmines

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 30, 2018

First Posted

May 25, 2018

Study Start

June 1, 2016

Primary Completion

September 1, 2018

Study Completion

September 1, 2018

Last Updated

December 3, 2019

Record last verified: 2018-05

Data Sharing

IPD Sharing
Will not share

Locations

US(3)