Metoclopramide Pilot Trial

The Use of Metoclopramide vs. Placebo in Infants With Gastroschisis. A Pilot Double Blind Randomized Controlled Trial

Infants with gastroschisis typically have poor intestinal motility for the first weeks to months after birth. Prokinetic agents are often used in these infants to improve intestinal motility in an attempt to quicken the attainment of enteric feeds. However, the evidence to support this practice remains weak. Investigators hypothesize that a prokinetic agent given intravenously (infused into a vein) may be effective in improving gut motility in children with gastroschisis.

Study Overview

• Status: Terminated
• Conditions: Gastroschisis
• Intervention / Treatment: Drug: intravenous metoclopramide; Other: Placebo

Detailed Description

The research question will be addressed in a pilot randomized double-blind placebo controlled clinical trial evaluating the efficacy of metoclopramide.Investigators will recruit 30 neonates (15 per arm) diagnosed with gastroschisis. There will be two arms to the trial: the experimental arm will receive intravenous metoclopramide and the control arm will receive placebo. Patients will receive prokinetic agent therapy, dosed according to weight, or placebo. Each subject will receive the intervention for 28 days or until achievement of full enteral feeding, whichever comes first. Primary outcome: Days to achieve full enteral feeding when all intake (at least 150 ml/kg/day for 72 hours) is given as breast milk or formula by gavage or by mouth. Secondary outcomes: 1. Duration (days) until initiation of enteral feeds. 2. Duration (days) on parenteral nutrition. 3. Weight gain, measured by grams per day per week during therapy. 4. Occurrence of adverse effects associated with the use of metoclopramide. 5. Rate of catheter-related sepsis episodes (line positive blood cultures necessitating antibiotic treatment or catheter removal). 6. Incidence of necrotizing enterocolitis (NEC) based on clinical criteria and presence of pneumatosis intestinalis on an abdominal X-ray. 7. Duration of hospitalization (number of days from admission until final hospital discharge).

Subjects can be withdrawn from the study if meet one of the following criteria:

• Subject develops extrapyramidal symptoms
• Subject has not established full enteral feeding by the end of day 28 of therapy
• Withdrawal of informed consent or refusal of further study participation by parent/legal guardian
• Serious adverse event which, in the opinion of the investigator, indicates that continued participation in the study is not in the best interest of the subject
• Any clinical adverse event, laboratory abnormality or intercurrent illness which, in the opinion of the investigator, indicates that continued participation in the study is not in the best interest of the subject
• Unpredictable discontinuation of metoclopramide drug supply

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of uncomplicated neonatal gastroschisis treated by primary fascial closure or delayed closure using a pre-formed silo (fascial closure or plastic closure)
2. Expectation of the treating physician that the patient will require intravenous therapy for at least 7 days post-enrolment

Exclusion Criteria:

1. Presence of other significant congenital malformation (ie life-threatening, requiring surgical intervention, or having an effect on intestinal motility)
2. Presence of intestinal atresia, intestinal necrosis or intestinal perforation (ie complicated gastroschisis)
3. Gestational age <32 weeks
4. Birth weight < 1500 gm
5. Received an investigational product within the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: intravenous metoclopramide; the experimental arm will receive intravenous metoclopramide	Drug: intravenous metoclopramide; the experimental arm will receive intravenous metoclopramide dosed according to the current Sick Kids guidelines based upon weight and age
PLACEBO_COMPARATOR: control arm; the control arm will receive placebo	Other: Placebo; equivalent volume to intravenous metoclopramide (dosed according to the current Sick Kids guidelines based upon weight and age ) of sterile sodium chloride 0.9% injection as a placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to achieve full enteral feeding	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Days to achieve full enteral feeding will be recorded when all intake (at least 150 ml/kg/day for 72 hours) is given as breast milk or formula by gavage or by mouth	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration until initiation of enteral feeds	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Duration (days) until initiation of enteral feeds will be recorded	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Duration on parenteral nutrition	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Duration (days) on parenteral nutrition will be recorded	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Weight gain	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Weight gain, measured by grams per day per week during therapy will be recorded	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Occurrence of adverse effects	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Occurrence of adverse effects associated with the use of metoclopramide will be recorded.	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Rate of catheter-related sepsis episodes	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Rate of catheter-related sepsis episodes during intravenous treatment (line positive blood cultures necessitating antibiotic treatment or catheter removal) will be recorded.	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Incidence of necrotizing enterocolitis (NEC)	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks. Incidence of necrotizing enterocolitis (NEC) during the therapy based on clinical criteria and presence of pneumatosis intestinalis on an abdominal X-ray will be recorded.	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Duration of hospitalization	Duration of hospitalization (number of days from admission until final hospital discharge) will be recorded.	Participants will be followed for the duration of hospital stay, an expected average of 4 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: The Physicians' Services Incorporated Foundation
• Investigators: Principal Investigator: Jacob C Langer, MD, University of Toronto

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): December 12, 2019
• Study Completion (ACTUAL): December 12, 2019

Study Registration Dates

• First Submitted: March 21, 2014
• First Submitted That Met QC Criteria: March 25, 2014
• First Posted (ESTIMATE): March 28, 2014

Study Record Updates

• Last Update Posted (ACTUAL): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: intestinal motility; gastroschisis; prokinetic agents; intravenous metoclopramide; time to full enteral feeding
• Additional Relevant MeSH Terms: Congenital Abnormalities; Musculoskeletal Diseases; Pathological Conditions, Anatomical; Hernia, Abdominal; Musculoskeletal Abnormalities; Hernia; Gastroschisis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Metoclopramide
• Other Study ID Numbers: 1000038585; 169334 (OTHER: Health Canada)