Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants

Study Overview
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Brief Summary
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Gastrografin is a radiopaque contrast agent for the gastrointestinal tract (GIT) which can be applied orally or rectally. In neonatal intensive care, Gastrografin is used to detect otherwise radiologically invisible perforations or an insufficient GIT anastomosis after surgery. Furthermore it is used for the treatment of meconium ileus. Gastrografin has a strong osmotic effect and leads to water influx into the intestine lumen. Thereby the peristaltic movement is accelerated and the premature infant excretes stool during the hours following application. Therefore Gastrografin might be effective to mobilize meconium from small bowel and deep parts of the colon. The investigators hypothesized that enteral application of Gastrografin accelerates meconium evacuation in premature infants, and thereby enhances feeding tolerance in this population.

Detailed Description
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In premature infants the establishment of proper gastrointestinal function is challenging and often associated with delayed meconium passage. Meconium evacuation depends on gestational age and birthweight: the more immature an infant is, the later meconium passage starts and the longer meconium passage lasts. The mean duration of meconium evacuation in premature infants with a gestational age below 30 weeks is 8 days, while mature infants excrete their meconium in 2 days. The obstruction of deep intestinal segments by tenacious, sticky meconium frequently leads to gastric residuals, a distended abdomen and delayed food passage. The time lag to full enteral feedings is extended, the probability to acquire infections due to intravenous access for parenteral nutrition increases and the hospital stay of the infant is prolonged. However, the relation between meconium passage and feeding tolerance remains controversial. While one study showed that there is little concordance between first meconium passage and feeding tolerance, an other one showed that rapid and complete excretion of meconium is crucial for oral feeding tolerance and has a positive effect on it. Recently, the investigators performed a prospective randomized trial to determine, whether repeated prophylactic applications of small volume glycerin enemas accelerate passage of meconium in very low birth weight (VLBW) infants. Disappointingly, application of enemas did not accelerate meconium evacuation. A possible reason for the ineffectiveness of glycerin enemas is that the volume used was too small to mobilize tenacious meconium sufficiently from the colon and small bowel. Gastrografin is a radiopaque contrast agent for the gastrointestinal tract (GIT) which can be applied orally or rectally. In neonatal intensive care, Gastrografin is used to detect otherwise radiologically invisible perforations or an insufficient GIT anastomosis after surgery. Furthermore it is used for the treatment of meconium ileus. Gastrografin has a strong osmotic effect and leads to water influx into the intestine lumen. Thereby the peristaltic movement is accelerated and the premature infant excretes stool during the hours following application. Therefore Gastrografin might be more effective to mobilize meconium from small bowel and deep parts of the colon. The investigators hypothesized, that enteral application of Gastrografin accelerates meconium evacuation in premature infants, and thereby enhances feeding tolerance in this population. The objective of the present study is to determine whether the enteral application of the osmotic contrast agent Gastrografin® accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants.

Official Title
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Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants- a Phase 4 Study

Conditions
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Meconium Ileus, Very Low Birth Weight Infant

Intervention / Treatment
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* Drug: Gastrografin
* Drug: Sterile water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: premature infants with a birthweight < 1500g and a gestational age < 32 weeks Exclusion Criteria: major congenital disorders chromosomal aberrations systemic metabolic disease and pre-existing gastrointestinal abnormalities (i.e. Morbus Hirschsprung) pre-existing conditions of severe hypotension

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gastrografin<br>infants receive 3ml/kg Gastrografin + 6ml/kg sterile water | Drug: Gastrografin<br>* Patients will receive 3ml Gastrografin + 6ml sterile water/kg as a single dose via a nasogastric tube during the first 24 hours of life.<br>* Other names: NDA-011245;|
| Placebo Comparator: Sterile water<br>infants receive 9ml/kg sterile water | Drug: Sterile water<br>* Patients will receive 9ml/kg sterile water as a single dose via a nasogastric tube during the first 24 hours of life.<br>* Other names: Sterile water (ANDA) #077393;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Complete Meconium Evacuation in Days | Time to complete meconium evacuation in days of life until the complete meconium evacuation from birth up to 40 days of life | days of life until until the complete meconium evacuation from birth up to 40 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feeding Tolerance- Full Enteral Feedings | full enteral feeding is defined in days of life from birth until an an infant tolerates an enteral feeding volume of 140ml/kg | days of life from birth until an infant tolerates en enteral feeding volume of 140 ml/kg | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLBW infant, Meconium, Enteral nutrition, Meconium passage