Official Title: “Should Very Low Birth Weight Infants Receive Enteral Nutrition During Indomethacin or Ibuprofen Treatment of a Patent Ductus Arteriosus? A Multi-Center Randomized Controlled Trial”

We hypothesize that feeding preterm infants while they receive indomethacin or ibuprofen therapy for treatment of a patent ductus arteriosus will decrease the incidence of feeding intolerance and shorten the time period that infants need to tolerate full enteral nutrition.

We also hypothesize that this intervention will minimize the alterations in intestinal permeability that occur with these drugs and will improve the infants' hemodynamic response to enteral nutrition

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2012

This study is a randomized controlled multi-center clinical trial to determine whether very low birth weight infants should receive feedings during indomethacin or ibuprofen treatment of a patent ductus arteriosus (PDA). Many neonatologists withhold feeds from premature infants receiving indomethacin or ibuprofen therapy for a PDA because of concerns that these drugs alter intestinal blood flow and permeability. However, there are no established studies which show that feeding during these medical treatments leads to bowel injury. At the same time, studies suggest that withholding feedings from premature infants may lead to intestinal atrophy and injury, leading to increased difficulty with feedings when they are initiated or re-started. Thus, this multi-center study evaluates whether feeding infants during indomethacin or ibuprofen therapy improves feeding tolerance by measuring the number of episodes of feeding intolerance and the number of days required to attain full feedings. In addition, this study will employ techniques to measure gastrointestinal permeability and mesenteric blood flow in patients who receive and don't receive feedings for their PDA treatment.

Intervention(s) in this Clinical Trial

• Other: feeding
  • Study infants will receive trophic enteral nutrition (15 ml/kg/day) during the study drug period.The study drug period is defined as the interval between administration of the first dose of ibuprofen or indomethacin and 24 hours after the last dose of ibuprofen or indomethacin.
• Other: fasting
  • Study infants will be fasted during the study drug period.The study drug period is defined as the interval between administration of the first dose of ibuprofen or indomethacin and 24 hours after the last dose of ibuprofen or indomethacin.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: ibuprofen-feeding
  • Study infants will receive trophic enteral nutrition (15 ml/kg/day) during the study drug period.The study drug period is defined as the interval between administration of the first dose of ibuprofen and 24 hours after the last dose of ibuprofen.
• No Intervention: ibuprofen-fasting
  • Study infants will be fasted during the study drug period.The study drug period is defined as the interval between administration of the first dose of ibuprofen and 24 hours after the last dose of ibuprofen.
• Experimental: indomethacin-feeding
  • Study infants will receive trophic enteral nutrition (15 ml/kg/day) during the study drug period.The study drug period is defined as the interval between administration of the first dose of indomethacin and 24 hours after the last dose of indomethacin.
• No Intervention: indomethacin-fasting
  • Study infants will be fasted during the study drug period.The study drug period is defined as the interval between administration of the first dose of indomethacin and 24 hours after the last dose of indomethacin.

Primary Measures

• Assess the effect of feeding infants during indomethacin or ibuprofen therapy on the incidence of feeding intolerance and the number of days required to achieve full feedings (120 ml/kg/day).
  • Time Frame: 4 years
    Safety Issue?: No

Secondary Measures

• incidence of necrotizing enterocolitis or spontaneous perforation
  • Time Frame: 4 years
    Safety Issue?: Yes
• Assess the effect of feeding very low birth weight infants during indomethacin or ibuprofen therapy on intestinal permeability.
  • Time Frame: 4 years
    Safety Issue?: No
• Assess the effect of feeding very low birth weight infants during indomethacin or ibuprofen therapy on the normal hyperemic response to feeding.
  • Time Frame: 4 years
    Safety Issue?: No

Inclusion Criteria:

• Infants between 401-1,250 g birth weight (delivered between 23 and 1/7 - 30 and 6/7 weeks gestation) who
• Are receiving or are scheduled to begin enteral feedings and
• Are about to receive pharmacologic treatment (either indomethacin or ibuprofen) to close their PDA.

Exclusion Criteria:

• Serious congenital malformations
• Chromosomal anomalies
• Congenital or acquired gastrointestinal anomalies
• Prior episode of necrotizing enterocolitis
• Use of inotropic support for hypotension
• Renal anomalies or disease
• Are receiving > 80 ml/kg/d of enteral feeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 23 Weeks

Maximum Age for this Clinical Trial: 30 Weeks

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, San Francisco

Overall Clinical Trial Officials and Contacts

Ronald Clyman, M.D. Principal Investigator University of California, San Francisco  

Overall Contact: Ronald Clyman, M.D. 415-476-4462 clymanr@peds.ucsf.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00728117

Study ID Number: RC3

ClinicalTrials.gov Identifier: NCT00728117

Health Authority: United States: Institutional Review Board