The Montefiore Metoclopramide Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Nausea, Extrapyramidal Symptoms

Intervention / Treatment
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* Drug: metoclopramide 10 mg
* Drug: Diphenhydramine 25 mg
* Drug: Placebo
* Drug: Metoclopramide 20 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metoclopramide, Nausea, Akathisia, Emergency department