Efficacy of Itopride Versus Metoclopramide in Hospitalized Medicine Patients With High Gastric Residual Volume (GRV)

Efficacy of Enteral Itopride Versus Intravenous Metoclopramide in Hospitalized Medicine Patients With Feeding Intolerance Causing by High Gastric Residual Volume: a Prospective Randomized Controlled Trial

A prospective randomized controlled trial included 86 patients in medicine ward who were diagnosed with feeding intolerance, defined as having a gastric residual volume greater than 200 ml. The patients were randomly assigned to two treatment groups: one receiving enteral metoclopramide and the other receiving intravenous metoclopramide. The primary outcome was the gastric residual volume at 72 hours after treatment. The secondary outcome was gastric residual volume at 24 hours and 7 days after treatment, administered-to-prescribed volume at 72 hours after treatment, the administered-to-target energy ratio and the administered-to-target protein ratio at 96 hours after treatment, the nutrition status evaluated by the Nutrition Alert Form at 7 days after treatment, incidence of adverse events (arrhythmia, pneumonia, diarrhea, vomiting, aspiration), length of hospital stay, ICU length of stay and in-hospital mortality.

Study Overview

• Status: Not yet recruiting
• Conditions: Feeding Intolerance
• Intervention / Treatment: Drug: Itopride HCI 50 mg; Drug: Metoclopramide 10 mg ampoule

Detailed Description

Feeding intolerance was a significant problem commonly encountered during enteral feeding and led to cessation of enteral feeding. Prokinetics was recommended in feeding intolerance patients with a gastric residual volume greater than 200 ml, in conjunction with addressing underlying causes of gastrointestinal motility dysfunction, such as electrolyte imbalances and hyperglycemia. In Thailand, Metoclopramide was frequently used as the prokinetic of choice. However, its use was associated with significant adverse effects, including QTc interval prolongation and extrapyramidal symptoms. As a result, there was a limitation of Metoclopramide use in patients with a prolonged QTc interval. Itopride was a novel prokinetic agent which did not cause QTc prolongation and did not cross the blood-brain barrier. A randomized double-blind study conducted in ICU patients demonstrated that itopride significantly reduced GRV compared to the metoclopramide group. However, there was only one study focusing on ICU populations including both medicine and surgery patients. Therefore, the aim of our study was to evaluate the efficacy of itopride compared to metoclopramide in reducing gastric residual volume in medicine patients, including both ICU and non-ICU settings.

Our study was a prospective randomized controlled trial included 86 patients in medicine ward who were diagnosed with feeding intolerance, defined as having a gastric residual volume greater than 200 ml. The inclusion criteria were hospitalized medical patients aged over 18 years who were receiving enteral feeding and had a gastric residual volume (GRV) ≥ 200 ml. The exclusion criteria were use of any prokinetic drug within 24 hours before participating in the study, known hypersensitivity or contraindication to Metoclopramide or Itopride, prolonged QTc interval > 460 milliseconds in female or >440 milliseconds in male, hemodynamic instability, GI surgery ≤ 6 weeks before enrollment in the study, history of esophagectomy or gastrectomy, pregnancy, suspicious or confirmed gastrointestinal obstruction or gastrointestinal hemorrhage or gastrointestinal perforation, epilepsy or currently use of anti-epileptic drug, acute CNS infection or severe brain injury, Parkinson's disease, confirmed or suspected pheochromocytoma, history of tardive dyskinesia and history of methemoglobinemia.

The primary outcome of the study was the gastric residual volume at 72 hours after treatment. The secondary outcome was gastric residual volume at 24 hours and 7 days after treatment, administered-to-prescribed volume at 72 hours after treatment, the administered-to-target energy ratio and the administered-to-target protein ratio at 96 hours after treatment, the nutrition status evaluated by the Nutrition Alert Form at 7 days after treatment, incidence of adverse events (arrhythmia, pneumonia, diarrhea, vomiting, aspiration), length of hospital stay, ICU length of stay and in-hospital mortality.

The sample size was calculated to be 84 patients, using a minimum clinically important difference (MCID) of 50, a standard deviation of 77.6 (as referenced from a previous study), a 1:1 ratio, an alpha error of 5%, and a beta error of 20%.

After enrollment, all patients were evaluated for and treated for reversible causes of feeding intolerance, including electrolyte imbalances and hyperglycemia. Nutritional status was also assessed prior to the initiation of therapy. The patients were randomly assigned to two treatment groups: one receiving enteral metoclopramide and the other receiving intravenous metoclopramide. Patients received prokinetic therapy for 7 days. A stepwise advancement to full enteral feeding-targeted at 25-30 kcal/kg/day-was implemented by Day 4. The gastric residual volume was recorded four times daily, prior to feeding, and measured in milliliters. The gastric residual volume was measured manually by the nurse from a different team to maintain blinding in the administration of prokinetics. If the gastric residual volume (GRV) exceeded 200 ml for at least two instances per day, feeding advancement was withheld. The study termination criteria included an inability to advance feeding for 48 hours, a GRV ≥ 400 mL on two occasions, and a QTc interval > 440 ms in males and > 460 ms in females. Both the nurses and the doctors assessing the gastric residual volume (GRV) were blinded to the study conditions.

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sasicha Kitphati, MD.; Phone Number: +66819244809; Email: kitphati.s@gmail.com
• Study Contact Backup: Name: Narisorn Lakananurak, MD.; Phone Number: +66853347979; Email: Narisorn.l@chula.ac.th

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospitalized medical patients aged over 18 years who were receiving enteral feeding and had a gastric residual volume (GRV) ≥ 200 ml

Exclusion Criteria:

• Use of any prokinetic drug within 24 hours before participating in the study
• Known hypersensitivity or contraindication to Metoclopramide or Itopride
• Prolonged QTc interval > 460 ms in female >440 ms in male
• Hemodynamic instability
• GI surgery ≤ 6 weeks before enrollment in the study
• History of esophagectomy or gastrectomy
• Pregnancy
• Suspicious or confirmed gastrointestinal obstruction or gastrointestinal hemorrhage or gastrointestinal perforation
• Epilepsy or currently use of anti-epileptic drug
• Acute CNS infection or severe brain injury
• Parkinson's disease
• Confirmed or suspected pheochromocytoma
• History of tardive dyskinesia, history of methemoglobinemia.

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
Experimental: Itopride; Enteral Itopride (50 mg enterally tid ac)	Drug: Itopride HCI 50 mg; Enteral Itopride 50 mg enterally tid ac
Active Comparator: Metoclopramide; Intravenous Metoclopramide (10 mg IV q 6 hours) CrCl 15-60 ml/min: Metoclopramide 5 mg IV q 6 hours CrCl <15 ml/min: Metoclopramide 5 mg IV q 12 hours Hepatic impairment/ cirrhosis: Metoclopramide 5 mg IV q 6 hours	Drug: Metoclopramide 10 mg ampoule; Intravenous Metoclopramide (10 mg IV q 6 hours) CrCl 15-60 ml/min: Metoclopramide 5 mg IV q 6 hours CrCl <15 ml/min: Metoclopramide 5 mg IV q 12 hours Hepatic impairment/ cirrhosis: Metoclopramide 5 mg IV q 6 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean gastric residual volume (in mL) on day 3 after initiation of prokinetics	Mean gastric residual volume (in mL) on day 3 after initiation of prokinetics. The gastric residual volume was recorded four times daily, prior to feeding.	Day3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean gastric residual volume (in mL) on day 1 after initiation of prokinetics	Mean gastric residual volume (in mL) on day 1 after initiation of prokinetics. The gastric residual volume was recorded four times daily, prior to feeding.	Day1
Mean gastric residual volume (in mL) on day 7 after initiation of prokinetics	Mean gastric residual volume (in mL) on day 7 after initiation of prokinetics. The gastric residual volume was recorded four times daily, prior to feeding.	Day 7
Percentage of prescribed enteral nutrition volume successfully administered on day 3 after initiation of prokinetics	Percentage of prescribed enteral nutrition volume successfully administered on day 3 after initiation of prokinetics. The goal total volume at day 3 was 1200 ml/day. (BD (1 kcal/1ml) 300 ml x 4 feed)	Day 3
Percentage of target enteral nutrition energy successfully administered on day 4 after initiation of prokinetics	Percentage of target enteral nutrition energy (30 kcal/kg in non-ICU patients, 25 kcal/kg in ICU patients) successfully administered on day 4 after initiation of prokinetics	Day 4
Percentage of target enteral nutrition protein successfully administered on day 4 after initiation of prokinetics	Percentage of target enteral nutrition protein (1.2 g/kg) successfully administered on day 4 after initiation of Prokinetics	Day 4
Rate of participants experiencing adverse events (Percentage)	Rate of participants experiencing adverse events (arrhythmia, pneumonia, diarrhea, vomiting, aspiration, abnormal movement)	Up to 7 days
Rate of In-Hospital mortality among Participants (Percentage)	Rate of In-Hospital mortality among participants (Percentage), measured from the initiation of prokinetics to the time of discharge.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Study Director: Narisorn Lakananurak, MD., Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: April 20, 2025
• First Submitted That Met QC Criteria: June 19, 2025
• First Posted (Actual): June 22, 2025

Study Record Updates

• Last Update Posted (Actual): June 22, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: metoclopramide; gastric residual volume; itopride
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neurotransmitter Agents; Dopamine Agents; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Metoclopramide
• Other Study ID Numbers: 0971/67

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes