Comparison of Ondansetron, Metoclopramide and Promethazine for the Treatment of Nausea and Vomiting in the Adult ED

• Sponsor: Vanderbilt University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00655642
• Collaborator: (none)
• Enrollment: 171
• Location: 1
• Arms: 4
• Duration (Months): 19.1
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness of ondansetron, metoclopramide, and promethazine for the treatment of nausea in the adult emergency department population.

We hypothesize that a single intravenous dose of ondansetron is more effective in reducing nausea than a single IV dose of metoclopramide, promethazine or normal saline placebo in undifferentiated adult emergency department patients.

Condition or Disease	Intervention/Treatment	Phase
Nausea	Drug: Ondansetron; Drug: Metoclopramide; Drug: Promethazine; Drug: Normal Saline	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 171 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, and Placebo-Controlled Trial Comparing Ondansetron, Metoclopramide and Promethazine for the Treatment of Nausea and Vomiting in the Adult Emergency Department.
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ondansetron Ondansetron 4 mg intravenous administration	Drug: Ondansetron; 4 mg intravenous dose administered over 2 minutes through a peripheral intravenous catheter
Active Comparator: Metoclopramide Metoclopramide 10 mg intravenous administration	Drug: Metoclopramide; 10 mg intravenous dose administered over 2 minutes through a peripheral intravenous catheter
Active Comparator: Promethazine Promethazine 10 mg intravenous administration	Drug: Promethazine; 12.5 mg intravenous dose administered over 2 minutes through a peripheral intravenous catheter
Placebo Comparator: Saline Placebo Volume-matched saline placebo	Drug: Normal Saline; Volume matched isotonic sodium chloride solution dose administered over 2 minutes through a peripheral intravenous catheter

Outcome Measures

Primary Outcome Measures

1. Change in Visual Analog Scale (VAS) Score for Nausea. This Was Calculated by Subtracting the Patient's Reported Score on the 30 Minute VAS From the Patient's Reported VAS Score on Their Baseline VAS. [Baseline and 30 minute assessments]

   Participants independently rated their nausea severity on separate scales at the baseline and 30-minute evaluations to prevent the baseline VAS score from influencing the 30-minute mark. The VAS had the words "Least Severe" on the left and "Most Severe" on the right. The possible values range from 0 to 100mm with 0 at the "Least Severe" extreme and 100 at the "Most Severe" extreme. Investigators instructed the participant to draw a single vertical line through the point on the 100mm scale that corresponded to their nausea severity at the times of measurement (Baseline and 30 minutes).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients age 18 or older who present to the ED with a complaint requiring antiemetic treatment who do not meet the exclusion criteria.

Exclusion Criteria:

• Patients less than 18 years of age

• Unstable patients with SBP < 90

• Patients with a stated or documented allergy to any of the study medications

• Patients whose nausea rating if < 40 on the pretreatment VAS scale

• Patients who have received a commonly accepted antiemetic within the previous 24 hours

• Patients unwilling or unable to complete the assessment tool before and 30 minutes after study drug dosing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37240

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: Tyler W Barrett, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tyler Barrett, Assistant Professor of Emergency Medicine, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00655642
• Other Study ID Numbers: VUMC 0612369
• First Posted: Apr 10, 2008
• Last Update Posted: Oct 30, 2013
• Last Verified: Sep 1, 2013

• Additional relevant MeSH terms: Nausea; Vomiting; Promethazine; Diphenhydramine; Ondansetron; Metoclopramide

Study Results

Participant Flow

Recruitment Details	Recruitment started March 2007 and completed October 2008. A covenience sample of all adult patients who presented to the emergency department (ED) with a complaint requiring antiemetic treatment who do not meet the exclusion criteria were considered for enrollment.
Pre-assignment Detail	Not applicable to this study

Arm/Group Title	Ondansetron	Metoclopramide	Promethazine	Placebo
Arm/Group Description	Patients randomized to a single 2 milliliter (mL) Ondansetron 4 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Metoclopramide 10 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Promethazine 12.5mg intravenous dosage administration treatment	Patients randomized to a single 2-mL isotonic sodium chloride Saline Placebo intravenous treatment
Period Title: Overall Study
STARTED	42	43	45	41
COMPLETED	41	40	43	39
NOT COMPLETED	1	3	2	2

Baseline Characteristics

Arm/Group Title	Ondansetron	Metoclopramide	Promethazine	Placebo	Total
Arm/Group Description	Patients randomized to a single 2 milliliter (mL) Ondansetron 4 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Metoclopramide 10 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Promethazine 12.5mg intravenous dosage administration treatment	Patients randomized to a single 2-mL isotonic sodium chloride Saline Placebo intravenous treatment	Total of all reporting groups
Overall Participants	42	43	45	41	171
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	37 88.1%	40 93%	43 95.6%	38 92.7%	158 92.4%
>=65 years	5 11.9%	3 7%	2 4.4%	3 7.3%	13 7.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.98 (16.895)	38.72 (16.076)	35.47 (16.036)	35.44 (14.589)	37.14 (15.882)
Sex: Female, Male (Count of Participants)
Female	27 64.3%	30 69.8%	31 68.9%	27 65.9%	115 67.3%
Male	15 35.7%	13 30.2%	14 31.1%	14 34.1%	56 32.7%
Region of Enrollment (participants) [Number]
United States	42 100%	43 100%	45 100%	41 100%	171 100%

Outcome Measures

1. Primary Outcome

Title	Change in Visual Analog Scale (VAS) Score for Nausea. This Was Calculated by Subtracting the Patient's Reported Score on the 30 Minute VAS From the Patient's Reported VAS Score on Their Baseline VAS.
Description	Participants independently rated their nausea severity on separate scales at the baseline and 30-minute evaluations to prevent the baseline VAS score from influencing the 30-minute mark. The VAS had the words "Least Severe" on the left and "Most Severe" on the right. The possible values range from 0 to 100mm with 0 at the "Least Severe" extreme and 100 at the "Most Severe" extreme. Investigators instructed the participant to draw a single vertical line through the point on the 100mm scale that corresponded to their nausea severity at the times of measurement (Baseline and 30 minutes).
Time Frame	Baseline and 30 minute assessments

Outcome Measure Data

Analysis Population Description

Analysis was performed on all patients who received one of the four treatments and completed the 30-minute VAS assessment. The trial was anticipated to require 18 months to achieve full accrual of patients (n=600). Given that we were at 30% information fraction at 17 months, an unplanned interim analysis was done.

Arm/Group Title	Ondansetron	Metoclopramide	Promethazine	Placebo
Arm/Group Description	Patients randomized to a single 2 milliliter (mL) Ondansetron 4 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Metoclopramide 10 mg intravenous dosage administration treatment	Patients randomized to a single 2 mL Promethazine 12.5mg intravenous dosage administration treatment	Patients randomized to a single 2-mL isotonic sodium chloride Saline Placebo intravenous treatment
Measure Participants	41	40	43	39
Median (Inter-Quartile Range) [millimeter]	-22.0	-30.0	-29.0	-16.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ondansetron, Metoclopramide, Promethazine, Placebo
	Comments	The null hypothesis is that ondanestron is not more effective in reducing nausea than metoclopramide, promethazine or isotonic normal saline. The sample size was chosen to detect a 12-mm difference in VAS improvement between ondanestron and any other treatment arm (assuming a SD of 25mm) at 90% power and 0.01 alpha significance level. We chose the 0.01 alpha level following a Bonferroni type of correction so that the overall type I error rate is about 0.05.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Based on the aforementioned values, we calculated a sample size for each treatment arm of 131 patients. We increased this sample estimate to 150 per treatment arm (total of 600 patients) to account for anticipated study attrition. Based on an unplanned interim conditional power futility analysis done at 30% information fraction, the decision was made to end the trial early.The futility analysis found the observed differences were far less than what was deemed clinically important.
Statistical Test of Hypothesis	p-Value	0.16
	Comments	Being aware of the multiple comparison issues, we deliberately chose the 0.01 alpha level following a Bonferroni type of correction so that the overall type I error rate is about 0.05.
	Method	Kruskal-Wallis
	Comments	We computed the effect of the 3 treatments relative to ondansetron.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	12
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 25
	Estimation Comments	Change in VAS score was calculated as (VAS 30 min - VAS baseline). We calculated the differences in median VAS reductions for each arm relative to ondansetron.

Adverse Events

Arm/Group Title	Ondansetron		Metoclopramide		Promethazine		Placebo
Arm/Group Description	Patients randomized to a single 2 milliliter (mL) Ondansetron 4 mg intravenous dosage administration treatment		Patients randomized to a single 2 mL Metoclopramide 10 mg intravenous dosage administration treatment		Patients randomized to a single 2 mL Promethazine 12.5mg intravenous dosage administration treatment		Patients randomized to a single 2-mL isotonic sodium chloride Saline Placebo intravenous treatment
All Cause Mortality
	Ondansetron		Metoclopramide		Promethazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ondansetron		Metoclopramide		Promethazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/43 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Ondansetron		Metoclopramide		Promethazine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/41 (24.4%)		18/40 (45%)		14/43 (32.6%)		9/39 (23.1%)
General disorders
Increased Sedation following treatment	3/41 (7.3%)		12/40 (30%)		11/43 (25.6%)		6/39 (15.4%)
Akathisia	0/41 (0%)		7/40 (17.5%)		0/43 (0%)		0/39 (0%)
Nervous system disorders
Headache following treatment	2/41 (4.9%)		2/40 (5%)		1/43 (2.3%)		4/39 (10.3%)
Skin and subcutaneous tissue disorders
Pain at iv site following medication administration	6/41 (14.6%)		3/40 (7.5%)		6/43 (14%)		1/39 (2.6%)

Limitations/Caveats

Early termination resulted in failure to meet our predetermined sample size.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.