The Montefiore Metoclopramide Study

A Randomized, Facorial Design Study to Optimize the Dose of Parenteral Metoclopramide

Metoclopramide is a dopamine antagonist frequently used for the treatment of nausea, vomiting, and migraine headaches in Emergency Departments. However, little research has focused on the optimal dose of metoclopramide for treatment of nausea in the emergency department. We propose a randomized, double-blind, placebo controlled trial to investigate the optimal dose of metoclopramide for treatment of nausea.

Study Overview

• Status: Completed
• Conditions: Nausea; Extrapyramidal Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: Diphenhydramine 25 mg; Drug: Metoclopramide 20 mg; Drug: metoclopramide 10 mg

Detailed Description

The most effective dose of metoclopramide for treatment of nausea in the emergency department setting has not been thoroughly investigated. One pilot study among emergency department patients in Australia found no statistical difference between 10 mg and 0.4 milligrams/kilogram; another investigation suggests that the anti-emetic effect of 10 milligrams of metoclopramide is no more effective than placebo. In contrast, investigations focusing on chemotherapy patients and post-operative patients suggest that higher dosage metoclopramide is more effective in treating nausea and vomiting. This emergency department study will compare the anti-emetic efficacy of 10 milligrams and 20 milligrams of metoclopramide by using the visual analog scale.

In addition to evaluation of dose, we will evaluate one of the most common side affects of metoclopramide, akathisia. Akathisia is characterized by a subjective component of restlessness and an objective component in the form of the inability to remain motionless. Anti-cholinergic medications are known to reduce extrapyramidal symptoms such as akathisia when dopamine function is impaired in the basal ganglia. In fact, the use of diphenhydramine has been shown to reduce the incidence of akathisia in patients receiving a different anti-emetic, prochlorperazine. However, no research has focused on the use of anti-cholinergic medications to reduce metoclopramide induced akathisia. This investigation will assess the use of 25 mg of diphenhydramine in preventing metoclopramide induced akathisia in ED patients being treated for nausea/vomiting.

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• primary or secondary complaints of nausea/vomiting
• age 21-65

Exclusion Criteria:

• pregnancy
• use of anti-histamine or dopamine antagonist as outpatient and/or within last 24 hours of presentation
• previous adverse reaction to study medications
• use of opioid medications prior to study start time within that ED visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metoclopramide 20+diphenhydramine; Metoclopramide 20 mg + diphenhydramine, delivered intravenously over 15 minutes	Drug: Diphenhydramine 25 mg; used for prophylaxis against akathisia; Drug: Metoclopramide 20 mg; Metoclopramide 20 mg
Active Comparator: Metoclopramide 20+placebo; Metoclopramide 20 mg + placebo, delivered intravenously over 15 minutes	Drug: Placebo; placebo; Drug: Metoclopramide 20 mg; Metoclopramide 20 mg
Active Comparator: Metoclopramide 10 + placebo; Metoclopramide 10mg + placebo, delivered intravenously over 15 minutes	Drug: Placebo; placebo; Drug: metoclopramide 10 mg; an anti-emetic medication
Active Comparator: Metoclopramide 10+diphenhydramine; Metoclopramide 10 mg + diphenhydramine 25 mg, delivered intravenously over 15 minutes	Drug: Diphenhydramine 25 mg; used for prophylaxis against akathisia; Drug: metoclopramide 10 mg; an anti-emetic medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea Scale	Patients were asked to report their level of nausea on a scale for 0 to 10, with 0 representing no nausea and 10 the worst nausea imaginable	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Akathisia	The akathisia outcome was reported as follows: Either development of akathisia as measured using the Short Akathisia Instrument (Vinson DR. Journal of Emergency Medicine. 2006; 31:139-145)or use of rescue medication for treatment of akathisia.The short akathisia instrument briefly measures subjective and objective restlessness.	60 minutes

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Study Director: Brooke Bender, MD, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Estimate): December 31, 2012
• Last Update Submitted That Met QC Criteria: November 28, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Nausea; Emergency department; Metoclopramide; Akathisia
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Dopamine Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Diphenhydramine; Promethazine; Metoclopramide
• Other Study ID Numbers: 07-01-005