Effects of butyrate enemas on postoperative intestinal motility disorders in Hirschsprung’s disease

This study evaluates the effects of butyrate enemas on postoperative intestinal motility disorders in patients with Hirschsprung's disease. The primary objective is to assess the short-term efficacy of preoperative butyrate enemas in reducing the time to recovery of bowel function after curative surgery in Hirschsprung's disease patients. This outcome is clinically relevant as delayed recovery of intestinal motility represents a significant postoperative complication that impacts patient recovery and hospital length of stay.

The secondary objectives include:

• Incidence of postoperative functional intestinal obstructive symptoms

• Evaluation of stool consistency

• Measurement of total intestinal transit time after surgery

• Incidence and grading of postoperative Hirschsprung-associated enterocolitis (HAEC)

• Measurement of postoperative intestinal inflammatory response

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of **newborns** diagnosed with **Hirschsprung's disease** within the first two months of life, encompassing both **male** and **female** participants. Eligible participants were required to have been born at or after 35 weeks of gestation and to present with **short-segment Hirschsprung's disease** limited to the **rectum** and/or **sigmoid colon**, confirmed by **rectal biopsy** demonstrating absence of **ganglionic cells** with or without hypertrophic extrinsic nerve fibres. The trial population was selected to include only uncomplicated cases without **enterocolitis** or diverting **colostomy**, and participants were required to have been successfully managed with colonic decompressions or irrigations prior to curative surgery. Participants with severe or lethal associated malformations were excluded from the study. This trial involved a vulnerable population, specifically neonates requiring specialized pediatric surgical intervention.

This is a phase III clinical trial investigating the effects of preoperative butyrate enemas on postoperative intestinal motility recovery in newborns with Hirschsprung's disease. The trial aims to assess the short-term efficacy of butyrate enemas at reducing the time to recovery of bowel function following curative surgery in patients with this condition. The study involves newborns diagnosed with Hirschsprung's disease within the first two months of life who have been successfully managed with colonic decompressions or irrigations prior to definitive surgical intervention. Eligible participants must be born at or after 35 weeks of gestation, have short-segment disease limited to the rectum and/or sigmoid colon confirmed by rectal biopsy showing absence of ganglionic cells, and present with an uncomplicated form without enterocolitis or diverting colostomy. The trial excludes newborns with severe or lethal associated malformations.

The investigational medicinal product is sodium butyrate 1.1 g/L solution prepared as an enema for rectal administration. The maximum daily dose is 10 units with a maximum total dose of 10 units over a treatment period of up to 4 weeks. A diagnostic agent is used as an auxiliary product with a maximum daily and total dose of 250 mg administered orally over a period of 1 day. The trial is designed to evaluate the efficacy of this intervention in the pediatric population affected by this rare disease.

The primary endpoint of the study is the time to recovery of bowel function after curative surgery. Secondary endpoints include assessment of postoperative functional intestinal obstructive symptoms, evaluation of stool consistency using the validated Bristol stool form scale modified for children, measurement of red carmine total intestinal transit time, documentation of HAEC episodes defined by the HAEC score with appropriate grading, and measurement of fecal calprotectin levels. These endpoints will provide comprehensive data on the postoperative intestinal function and potential inflammatory processes in the study population.

The estimated recruitment period for the trial is scheduled to begin in February 2026, with an estimated completion date in August 2031, indicating an overall trial duration of approximately 5.5 years. Participant involvement extends from the preoperative period through the administration of butyrate enemas, curative surgery, and subsequent postoperative follow-up assessments. The duration of individual participant involvement includes the preoperative treatment phase of up to 4 weeks and the postoperative monitoring period necessary to assess recovery of bowel function and evaluate the specified endpoints. Conditions that may lead to early termination from the study include development of severe complications, withdrawal of parental consent, protocol violations, or determination by the investigator that continued participation is not in the best interest of the participant.

The experimental treatment in this clinical trial consists of **sodium butyrate** administered as an **enema**. The pharmaceutical form is a solution for preparation with a concentration of 1.1 g/L. The active substance, sodium butyrate, is of chemical origin. The maximum daily dose is 10 units, with a maximum total dose of 10 units administered over a treatment period of 4 weeks. The route of administration is classified as other use, specifically via rectal enema. This investigational medicinal product does not currently have an assigned therapeutic class and is not formulated as a **paediatric formulation**.

A diagnostic agent is also utilized in this study as an auxiliary medicinal product. This agent is classified under **ATC code** V04CX, which corresponds to other diagnostic agents. The pharmaceutical form is identified as PHF00006MIG. The maximum daily dose and maximum total dose are both 250 mg, administered over a treatment period of 1 day. The route of administration for this diagnostic agent is **oral use**. This product serves a supportive role in the clinical investigation and is not the primary experimental intervention.

Efficacy will be assessed using the time to recovery of bowel function after curative surgery as the primary endpoint. Secondary endpoints include the assessment of postoperative functional intestinal obstructive symptoms, stool consistency evaluated using the validated Bristol stool form scale modified for children, red carmine total intestinal transit time measurement, episodes of Hirschsprung-associated enterocolitis defined by the HAEC score and grading, and fecal calprotectin measurement.