Feeding During Ibuprofen or Indomethacin Treatment of Preterm Infants

Study Overview
=================
Brief Summary
-----------------
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

Detailed Description
-----------------
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.

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

Conditions
-----------------
Patent Ductus Arteriosus

Intervention / Treatment
-----------------
* Other: feeding
* Other: fasting


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants between 401-1,250 g birth weight 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

Ages Eligible for Study
-----------------
Minimum Age: 23 Weeks
Maximum Age: 33 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ibuprofen-feeding<br>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. | Other: feeding<br>* 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.<br>|
| Experimental: ibuprofen-fasting<br>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. | Other: fasting<br>* 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.<br>|
| Experimental: indomethacin-feeding<br>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. | Other: feeding<br>* 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.<br>|
| Experimental: indomethacin-fasting<br>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. | Other: fasting<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of necrotizing enterocolitis or spontaneous perforation |  | 4 years | 
| Assess the effect of feeding very low birth weight infants during indomethacin or ibuprofen therapy on intestinal permeability. |  | 4 years | 
| Assess the effect of feeding very low birth weight infants during indomethacin or ibuprofen therapy on the normal hyperemic response to feeding. |  | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
indomethacin, ibuprofen, preterm infant