NCT00009646

Brief Summary

This trial was to determine whether giving low-dose indomethacin to infants weight 500 to 999 grams (approximately 1 to 2 pounds) at birth improves their survival without cerebral palsy or developmental problems at 18 to 22 months of age.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
1,202

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Nov 1993

Longer than P75 for phase_3

Geographic Reach
1 country

9 active sites

Status
completed

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

November 1, 1993

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 1999

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

February 1, 2001

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 5, 2001

Completed
24 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2001

Completed
Last Updated

June 8, 2015

Status Verified

June 1, 2015

Enrollment Period

5.3 years

First QC Date

February 1, 2001

Last Update Submit

June 3, 2015

Conditions

Infant, Very Low Birth WeightInfant, PrematureDuctus Arteriosus, Patent

Keywords

Chronic lung diseaseIndocinIndomethacinInfants, very low birth weightIntraventricular hemorrhageNecrotizing enterocolitisPatent ductus arteriosusPulmonary hemorrhage

Outcome Measures

Primary Outcomes (1)

  • Death or Neurodevelopment Impairment

    18-22 Months Corrected Age

Secondary Outcomes (6)

  • Patent ductus arteriosus

    120 Days of Life

  • Bronchopulmonary Dysplasia (BPD)

    120 Days of Life

  • Necrotizing enterocolitis (NEC)

    120 Days of Life

  • Intracranial abnormalities

    120 Days of Life

  • Retinopathy of Prematurity (ROP)

    18-22 Months Corrected Age

  • +1 more secondary outcomes

Study Arms (2)

Indomethacin

EXPERIMENTAL

Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa.

Drug: indomethacin

Placebo

PLACEBO COMPARATOR

Saline solution

Drug: Placebo

Interventions

IndomethacinDRUG

Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa

Indomethacin
PlaceboDRUG

0.1 mg per kilogram of body weight

Placebo

Eligibility Criteria

Age2 Hours - 6 Hours
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Birth weight 500 to 999 grams;
  • Postnatal age greater than 2 hours;

You may not qualify if:

  • Unable to administer study drug within 6 hours of birth;
  • Structural heart disease and/or renal disease;
  • Dysmorphic features or congenital abnormalities;
  • Tocolytic therapy with indomethacin or other prostaglandin inhibitor within 72 hours prior to delivery;
  • Overt clinical bleeding from more than one site;
  • Platelet count less than 50 x 109/L;
  • Hydrops;
  • Not considered viable

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Related Publications (9)

  • Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, Solimano A, Vincer M, Wright LL; Trial of Indomethacin Prophylaxis in Preterms Investigators. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med. 2001 Jun 28;344(26):1966-72. doi: 10.1056/NEJM200106283442602.

    PMID: 11430325RESULT

  • Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003 Mar 5;289(9):1124-9. doi: 10.1001/jama.289.9.1124.

    PMID: 12622582RESULT

  • Ambalavanan N, Baibergenova A, Carlo WA, Saigal S, Schmidt B, Thorpe KE; Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Early prediction of poor outcome in extremely low birth weight infants by classification tree analysis. J Pediatr. 2006 Apr;148(4):438-444. doi: 10.1016/j.jpeds.2005.11.042.

    PMID: 16647401RESULT

  • Schmidt B, Roberts RS, Fanaroff A, Davis P, Kirpalani HM, Nwaesei C, Vincer M; TIPP Investigators. Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP). J Pediatr. 2006 Jun;148(6):730-734. doi: 10.1016/j.jpeds.2006.01.047.

    PMID: 16769377RESULT

  • Clyman RI, Saha S, Jobe A, Oh W. Indomethacin prophylaxis for preterm infants: the impact of 2 multicentered randomized controlled trials on clinical practice. J Pediatr. 2007 Jan;150(1):46-50.e2. doi: 10.1016/j.jpeds.2006.09.001.

    PMID: 17188612RESULT

  • Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A; Trial of Indomethacin Prophylaxis in Preterms Investigators. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms. J Pediatr. 2007 Mar;150(3):229-34, 234.e1. doi: 10.1016/j.jpeds.2006.11.039.

    PMID: 17307535RESULT

  • Alfaleh K, Smyth JA, Roberts RS, Solimano A, Asztalos EV, Schmidt B; Trial of Indomethacin Prophylaxis in Preterms Investigators. Prevention and 18-month outcomes of serious pulmonary hemorrhage in extremely low birth weight infants: results from the trial of indomethacin prophylaxis in preterms. Pediatrics. 2008 Feb;121(2):e233-8. doi: 10.1542/peds.2007-0028.

    PMID: 18245398RESULT

  • Bassler D, Stoll BJ, Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS; Trial of Indomethacin Prophylaxis in Preterms Investigators. Using a count of neonatal morbidities to predict poor outcome in extremely low birth weight infants: added role of neonatal infection. Pediatrics. 2009 Jan;123(1):313-8. doi: 10.1542/peds.2008-0377.

    PMID: 19117897RESULT

  • Schmidt B, Seshia M, Shankaran S, Mildenhall L, Tyson J, Lui K, Fok T, Roberts R; Trial of Indomethacin Prophylaxis in Preterms Investigators. Effects of prophylactic indomethacin in extremely low-birth-weight infants with and without adequate exposure to antenatal corticosteroids. Arch Pediatr Adolesc Med. 2011 Jul;165(7):642-6. doi: 10.1001/archpediatrics.2011.95.

    PMID: 21727276DERIVED

Related Links

MeSH Terms

Conditions

Premature BirthDuctus Arteriosus, PatentEnterocolitis, Necrotizing

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesHeart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesEnterocolitisGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

IndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Barbara Schmidt, MD

    McMaster University

    STUDY DIRECTOR

  • David K. Stevenson, MD

    Stanford University

    PRINCIPAL INVESTIGATOR

  • Lu-Ann Papile, MD

    University of New Mexico

    PRINCIPAL INVESTIGATOR

  • Jon E. Tyson, MD MPH

    University of Texas

    PRINCIPAL INVESTIGATOR

  • Waldemar A. Carlo, MD

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

  • Seetha Shankaran, MD

    Wayne State University

    PRINCIPAL INVESTIGATOR

  • Barbara J. Stoll, MD

    Emory University

    PRINCIPAL INVESTIGATOR

  • Avroy A. Fanaroff, MD

    Case Western Reserve University

    PRINCIPAL INVESTIGATOR

  • Charles R. Bauer, MD

    University of Miami

    PRINCIPAL INVESTIGATOR

  • William Oh, MD

    Brown University, Womens and Infants Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NETWORK

Study Record Dates

First Submitted

February 1, 2001

First Posted

February 5, 2001

Study Start

November 1, 1993

Primary Completion

March 1, 1999

Study Completion

March 1, 2001

Last Updated

June 8, 2015

Record last verified: 2015-06

Locations

US(9)