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

NCT ID: NCT07031479

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2026-09-30

Brief Summary

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.

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.

Conditions

Feeding Intolerance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Itopride

Enteral Itopride (50 mg enterally tid ac)

Group Type: EXPERIMENTAL

Itopride HCI 50 mg

Intervention Type: DRUG

Enteral Itopride 50 mg enterally tid ac

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

Group Type: ACTIVE_COMPARATOR

Metoclopramide 10 mg ampoule

Intervention Type: DRUG

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

Interventions

Itopride HCI 50 mg

Enteral Itopride 50 mg enterally tid ac

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chulalongkorn University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Narisorn Lakananurak, MD.

Role: STUDY_DIRECTOR

Chulalongkorn University

Central Contacts

Sasicha Kitphati, MD.

Role: CONTACT

kitphati.s@gmail.com

+66819244809

Narisorn Lakananurak, MD.

Role: CONTACT

Narisorn.l@chula.ac.th

+66853347979

Other Identifiers

0971/67

Identifier Type: -

Identifier Source: org_study_id