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

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

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.

Study Overview

• Status: Completed
• Conditions: Meconium Ileus; Very Low Birth Weight Infant
• Intervention / Treatment: Drug: Gastrografin; Drug: Sterile water

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nadja Haiden,MD
• Investigators: Principal Investigator: Nadja Haiden, MD, Medical University of Vienna, Department of Pediatrics

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: January 10, 2012
• First Submitted That Met QC Criteria: January 23, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Meconium; Enteral nutrition; VLBW infant; Meconium passage
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Body Weight; Birth Weight; Meconium Ileus
• Other Study ID Numbers: 27112001; 2007-000851-33 (EudraCT Number)