Glycerin Suppositories Used Prophylactically in Premature infants (SUPP): A pilot study for a multicentre randomized controlled trial

Abstract

BACKGROUND: Adequate feeding is a significant challenge for premature infants in the neonatal intensive care unit. These patients are often treated with glycerin suppositories to stimulate the passage of meconium and prevent feeding intolerance. Unfortunately, the evidence for this practice is limited and inconclusive.

METHODS: We conducted a systematic review on the use of glycerin suppositories and enemas in premature infants. Following this, we conducted a pilot study for a multicenter randomized controlled trial of premature infants randomized to glycerin suppositories or a placebo procedure once daily. Outcomes included rate of recruitment, rate of reaching the primary endpoint of full enteral feeds, treatment-related adverse events, and cost.

RESULTS: Twenty-two infants were recruited and randomized active treatment or the placebo procedure. Gestational age was 24-32 weeks and birth weight was 500-1500 grams. During the study period, 61 infants were screened, 46 (75%) were eligible and approached for consent, 25 (54%) consented to participate, 22 (48%) were randomized, and 19 reached the primary endpoint of full enteral feeds. Three infants (14%) experienced rectal bleeding 5 to 43 days after completing study treatments. An anal fissure was also noted in two of these patients (9%). There were no cases of rectal perforation or necrotizing enterocolitis. Protocol violations occurred during 14 of 130 (11%) treatment days. The total cost for running this pilot study was estimated to be $16,000. A revised sample size calculation for the multicenter study indicated that 72 infants would be required to detect a treatment effect of 2 days faster to full enteral feeds.

CONCLUSIONS: This external pilot study suggested that conducting a multicenter randomized controlled trial of glycerin suppositories in premature infants is feasible and safe. In the multicenter trial, we recommend tolerating a lower platelet count in the exclusion criteria, using a fixed rather than variable treatment duration, conducting follow-up assessments at predefined time points, and conducting an interim analysis to ensure that treatment is not associated with increased risk of necrotizing enterocolitis.