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| ID | Type | Description | Link |
|---|---|---|---|
| U10HD034216 | U.S. NIH Grant/Contract | View source | |
| U10HD027904 | U.S. NIH Grant/Contract | View source | |
| U10HD021364 | U.S. NIH Grant/Contract | View source | |
| U10HD027851 | U.S. NIH Grant/Contract | View source | |
| U10HD021397 | U.S. NIH Grant/Contract | View source | |
| U10HD027881 | U.S. NIH Grant/Contract | View source | |
| U10HD027880 | U.S. NIH Grant/Contract | View source | |
| U10HD021373 | U.S. NIH Grant/Contract | View source | |
| U10HD021385 | U.S. NIH Grant/Contract | View source | |
| MT-13288 | Other Grant/Funding Number | Medical Research Council of Canada | |
| M01RR000997 | U.S. NIH Grant/Contract | View source | |
| M01RR000070 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Medical Research Council of Canada | OTHER |
| National Center for Research Resources (NCRR) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Indomethacin | Experimental | Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa. |
|
| Placebo | Placebo Comparator | Saline solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| indomethacin | Drug | Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa |
|
| Measure | Description | Time Frame |
|---|---|---|
| Death or Neurodevelopment Impairment | 18-22 Months Corrected Age |
| Measure | Description | Time Frame |
|---|---|---|
| Patent ductus arteriosus | 120 Days of Life | |
| Bronchopulmonary Dysplasia (BPD) | Chronic Lung Disease (CLD) | 120 Days of Life |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11430325 | Result | 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. | |
| 12622582 | Result | 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. |
| Label | URL |
|---|---|
| NICHD Neonatal Research Network | View source |
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| Indomethacin | Drug | 0.1 mg per kilogram of body weight |
|
| Placebo | Drug | 0.1 mg per kilogram of body weight |
|
| Necrotizing enterocolitis (NEC) |
| 120 Days of Life |
| Intracranial abnormalities | 120 Days of Life |
| Retinopathy of Prematurity (ROP) | 18-22 Months Corrected Age |
| Pulmonary hemorrhage | 120 Days of Life |
| Brown University, Womens and Infants Hospital |
| Principal Investigator |
| Palo Alto |
| California |
| 94304 |
| United States |
| University of Miami | Miami | Florida | 33136 | United States |
| Emory University | Atlanta | Georgia | 30303 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| University of New Mexico | Albuquerque | New Mexico | 87131 | United States |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| Brown University, Women & Infants Hospital of Rhode Island | Providence | Rhode Island | 02905 | United States |
| University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | 75235 | United States |
| 16647401 | Result | 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. |
| 16769377 | Result | 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. |
| 17188612 | Result | 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. |
| 17307535 | Result | 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. |
| 18245398 | Result | 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. |
| 19117897 | Result | 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. |
| 21727276 | Derived | 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. |
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| D004374 | Ductus Arteriosus, Patent |
| D020345 | Enterocolitis, Necrotizing |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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