Comparison of Diltiazem and Metoprolol in the Management of Acute Atrial Fibrillation or Atrial Flutter (DiME)

May 1, 2014 updated by: Antonios Likourezos

DiME Study: Comparison of Diltiazem and Metoprolol in the Management of Acute Atrial Fibrillation or Atrial Flutter With Rapid Ventricular Response: A Prospective Randomized and Double-Blinded Non-Inferiority Trial of Safety and Efficacy

Acute atrial fibrillation is the most common sustained, clinically significant dysrhythmia encountered in the emergency department (ED) and the most common dysrhythmia treated by emergency physicians. Atrial flutter is less common than atrial fibrillation but its management in the ED is very similar, and the majority of patients with atrial flutter also have atrial fibrillation. Symptomatic relief and ventricular rate control are generally the primary therapeutic objectives in the ED management of acute atrial fibrillation and flutter (AFF). The need for swift, appropriate action by the emergency physician is highlighted by the fact that up to 18% of patients with AFF develop potentially life-threatening complications such as congestive heart failure, hypotension, ventricular ectopy, respiratory failure, angina and myocardial infarction.

Both beta-blocking agents and calcium channel blockers are commonly used to treat AFF in the ED. Metoprolol is the most commonly used beta-blocker; and diltiazem is the most frequently used calcium channel antagonist.[8] Diltiazem was released by the FDA for treatment of AFF in 1992. Shreck et al. were the first to demonstrate both the efficacy of diltiazem in the ED management of AFF with rapid rate and its clear superiority over the previously most commonly used pharmacologic agent, digoxin.

To date, only one prospective, randomized trial has compared the effectiveness of a calcium channel blocker (diltiazem) with a beta-blocker (metoprolol) for rate control of AFF in the ED. Despite the relatively small sample size (n=20 in each group) the authors concluded that both pharmacologic agents were similarly effective. In order to test this finding, the investigators conducted a prospective comparison of metoprolol and diltiazem for the management of patients presenting to the ED with AFF with rapid ventricular rate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

We conducted a prospective, randomized, double-blind study to compare the effectiveness of intravenous metoprolol with that of diltiazem in achieving rate control in adult ED patients with rapid atrial fibrillation or flutter. Approval of the study was obtained from our hospital's institutional review board. All enrolled patients provided written informed consent and HIPAA authorization documentation.

This study was set in the adult ED of Maimonides Medical Center, an urban teaching hospital in Brooklyn, NY with an annual ED census of more than 120,00 patients. A convenience sample of adult patients age 18 or older presenting with a supraventricular tachydysrhythmia were evaluated for enrollment. Eligible patients had to have a 12-lead electrocardiogram (ECG) showing atrial fibrillation or atrial flutter with a ventricular rate of greater than or equal to 120 beats per minute. Data collected included demographics, medical history, vital signs and electrocardiogram findings. All patients were immediately evaluated by the treating physician utilizing ACLS protocols. At the discretion of the treating physician, intravenous adenosine was administered in order to facilitate identification of the underlying supraventricular tachydysrhythmia. All patients were attached to a monitor that displays cardiac rhythm, heart rate, blood pressure and oxygen saturation.

Upon enrollment, patients were randomly assigned, in a 1:1 ratio, to receive diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg) or metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg). Randomization was performed through the use of a computer-generated randomization list. Pharmacy released the study drug in a locked tackle box coded in number sequence to correspond to that of the computer-generated randomization list, upon which the pharmacist also prepared the study drug in blinded fashion. The study medications were packaged in identical-appearing dispensing kits. Patients who were randomly assigned to diltiazem received a bolus injection in a syringe that appeared identical to that of metoprolol. Admixture and labeling were performed by the pharmacist in the ED and dispensed to the treating nurse for administration. Doses of each study medication were adjusted with normal saline to a total of 10 ml in each syringe to prevent un-blinding. The time at which the first dose was administered was denoted as time zero (baseline). If the primary endpoint was not achieved at time 15 minutes, then a second escalation dose was administered. If the patient had been enrolled in the diltiazem group, the escalation dose was 0.35 mg/kg (to a maximum dose of 30 mg), and for patients enrolled in the metoprolol group, the escalation dose was 0.25 mg/kg (to a maximum dose of 10 mg). As with the initial dose, the escalation dose was prepared by the pharmacist and given to the treating nurse for patient administration in a blinded fashion.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Brooklyn, New York, United States, 11219
        • Maimonides Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Eligible patients had to have a 12-lead electrocardiogram (ECG) showing atrial fibrillation or atrial flutter with a ventricular rate of greater than or equal to 120 beats per minute and a systolic blood pressure of greater than or equal to 90 mmHg.

Exclusion Criteria:

Patients were excluded if they had any of the following:

  • a systolic blood pressure <90 mmHg, ventricular rate greater than or equal to 220 beats per minute,
  • QRS >0.100 seconds, 2nd or 3rd degree atrioventricular (AV) block,
  • temperature >38.0 ˚C,
  • acute ST elevation myocardial infarction,
  • known history of New York Heart Association Class IV heart failure or
  • active wheezing with a history of bronchial asthma or COPD.

In addition, patients were excluded if there was:

  • prehospital administration of diltiazem or any other AV nodal blockading agent,
  • a history of cocaine or methamphetamine use in the previous 24 hours prior to arrival,
  • a history of allergic reaction to diltiazem or metoprolol,
  • a history of sick sinus or pre-excitation syndromes,
  • a history of anemia with hemoglobin <11.0 g/dl,
  • pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metoprolol Study Group
Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg)
Drug: Metoprolol
Active Comparator: Diltiazem Study Group
Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg)
Drug: Diltiazem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Patients Reaching Target HR<100bpm Within 30 Minutes
Time Frame: 30 minutes
Percent of patient who reached a HR<100bpm within 30 minutes from baseline.
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Antonios Likourezos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

July 11, 2013

First Submitted That Met QC Criteria

July 31, 2013

First Posted (Estimate)

August 2, 2013

Study Record Updates

Last Update Posted (Estimate)

May 15, 2014

Last Update Submitted That Met QC Criteria

May 1, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09/01/VA02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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