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Infant, Very Low Birth WeightPhase 3TIPPNCT00009646

Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)

A Phase 3 study testing indomethacin in people with Infant, Very Low Birth Weight and Infant, Premature, run by NICHD Neonatal Research Network at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 6 hours
What is being tested?
indomethacin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,202 participants
Where
9 sitesUnited States
Study dates
Nov 1993to Mar 2001
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 6 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Emory University

    Atlanta, Georgia, 30303

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

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

    Cleveland, Ohio, 44106

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75235

  • Wayne State University

    Detroit, Michigan, 48201

  • University of Miami

    Miami, Florida, 33136

  • Stanford University

    Palo Alto, California, 94304

  • Brown University, Women & Infants Hospital of Rhode Island

    Providence, Rhode Island, 02905

Other trials in United States

About this study

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.

Read the detailed description

Prophylactic indomethacin reduces patent ductus arteriosus (PDA) and intraventricular hemorrhage in very low birth weight infants. However, the effects of early indomethacin on long-term neurodevelopment remain uncertain. There is also insufficient evidence to rule out serious adverse effects, such as increases in the risk of necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The aim of this trial was to determine if prophylactic administration of indomethacin improves survival without neurosensory impairments in extremely-low-birth-weight infants. Infants (n=1202) with birthweights 500 to 999 grams were randomized between 2 and 6 hours after birth to receive either intravenous indomethacin (0.1 mg/kg) or equal volumes of normal saline placebo, daily for 3 days. The primary outcomes at a corrected age of 18 months was a composite of death, cerebral palsy, cognitive delay, deafness, or blindness. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, cranial ultrasonographic abnormalities, nectrotizing enterocolitis and retinopathy. Infants were evaluated in follow-up at 18-22 months corrected age.

Being tested
indomethacin, Placebo
Keywords
Chronic lung disease, Indocin, Indomethacin, Infants, very low birth weight, Intraventricular hemorrhage, Necrotizing enterocolitis, Patent ductus arteriosus, Pulmonary hemorrhage
Medical subject headings
Premature Birth, Ductus Arteriosus, Patent, Enterocolitis, Necrotizing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • indomethacinDrug

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

  • IndomethacinDrug

    0.1 mg per kilogram of body weight

  • PlaceboDrug

    0.1 mg per kilogram of body weight

Study groups in NCT00009646
Study groupRoleWhat they receive
IndomethacinExperimentalIndocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa.
Receives: Drug: indomethacin
PlaceboPlacebo comparatorSaline solution
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Death or Neurodevelopment Impairment

    Measured: 18-22 Months Corrected Age

Secondary outcomes (6)

  1. Patent ductus arteriosus

    Measured: 120 Days of Life

  2. Bronchopulmonary Dysplasia (BPD)

    Chronic Lung Disease (CLD)

    Measured: 120 Days of Life

  3. Necrotizing enterocolitis (NEC)

    Measured: 120 Days of Life

  4. Intracranial abnormalities

    Measured: 120 Days of Life

  5. Retinopathy of Prematurity (ROP)

    Measured: 18-22 Months Corrected Age

  6. Pulmonary hemorrhage

    Measured: 120 Days of Life

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2001 (estimated)
  2. Study startNov 1993
  3. Primary completionMar 1999
  4. Study completionMar 2001

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00009646
Sponsor's protocol ID
NICHD-NRN-0011
Other IDs
U10HD034216, U10HD027904, U10HD021364, U10HD027851, U10HD021397, U10HD027881, U10HD027880, U10HD021373
Acronym
TIPP
Status last verified
Jun 2015
First submitted
1 Feb 2001
Last updated
8 Jun 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 11430325

  • 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.

    PubMed 12622582

  • 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.

    PubMed 16647401

  • 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.

    PubMed 16769377

  • 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.

    PubMed 17188612

  • 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.

    PubMed 17307535

  • 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.

    PubMed 18245398

  • 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.

    PubMed 19117897

  • 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.

    PubMed 21727276

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing indomethacin in people with Infant, Very Low Birth Weight and Infant, Premature, run by NICHD Neonatal Research Network at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Death or Neurodevelopment Impairment (time frame: 18-22 Months Corrected Age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00009646, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2015.

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