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

Sponsor
Antonios Likourezos (Other)
Overall Status
Completed
CT.gov ID
NCT01914926
Collaborator
(none)
54
Enrollment
1
Location
2
Arms
17
Duration (Months)
3.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Nov 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Percent of Patients Reaching Target HR<100bpm Within 30 Minutes [30 minutes]

    Percent of patient who reached a HR<100bpm within 30 minutes from baseline.

Eligibility Criteria

Criteria

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Maimonides Medical Center Brooklyn New York United States 11219

Sponsors and Collaborators

  • Antonios Likourezos

Investigators

  • Study Chair: John Marshall, MD, Maimonides Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Antonios Likourezos, Research Manager, Maimonides Medical Center
ClinicalTrials.gov Identifier:
NCT01914926
Other Study ID Numbers:
  • 09/01/VA02
First Posted:
Aug 2, 2013
Last Update Posted:
May 15, 2014
Last Verified:
May 1, 2014
Keywords provided by Antonios Likourezos, Research Manager, Maimonides Medical Center
metoprolol
diltiazem
heart rate
Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Metoprolol
Diltiazem

Study Results

Participant Flow

Recruitment Details Recruitment of patients was from June 2009 to November 2010
Pre-assignment Detail No significant events
Arm/Group Title Metoprolol Study Group Diltiazem Study Group
Arm/Group Description Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg) Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg)
Period Title: Overall Study
STARTED 29 25
COMPLETED 28 24
NOT COMPLETED 1 1

Baseline Characteristics

Arm/Group Title Metoprolol Study Group Diltiazem Study Group Total
Arm/Group Description Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg) Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg) Total of all reporting groups
Overall Participants 29 25 54
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
11
37.9%
13
52%
24
44.4%
>=65 years
18
62.1%
12
48%
30
55.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
68.95
(14.94)
65.85
(13.22)
67.52
(14.12)
Sex: Female, Male (Count of Participants)
Female
17
58.6%
15
60%
32
59.3%
Male
12
41.4%
10
40%
22
40.7%
Region of Enrollment (participants) [Number]
United States
29
100%
25
100%
54
100%

Outcome Measures

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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Study Group Diltiazem Study Group
Arm/Group Description Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg) Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg)
Measure Participants 28 24
Number [percentage of participants]
46.4
160%
95.8
383.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metoprolol Study Group, Diltiazem Study Group
Comments We estimated a sample size of 200 patients assigned in a 1:1 ratio to receive diltiazem and metoprolol would achieve 80% power to detect non-inferiority using a one-sided two sample t-test. The margin of equivalence is -10.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Chi-Square test
Statistical Test of Hypothesis p-Value .0001
Comments
Method Chi-squared
Comments

Adverse Events

Time Frame
Adverse Event Reporting Description
Arm/Group Title Metoprolol Study Group Diltiazem Study Group
Arm/Group Description Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg) Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg)
All Cause Mortality
Metoprolol Study Group Diltiazem Study Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Metoprolol Study Group Diltiazem Study Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/29 (0%) 0/25 (0%)
Other (Not Including Serious) Adverse Events
Metoprolol Study Group Diltiazem Study Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/29 (0%) 0/25 (0%)

Limitations/Caveats

[Not Specified]

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.

Results Point of Contact

Name/Title Christian Fromm, MD; Director of Research
Organization Maimonides Medical Center
Phone 718-283-6391
Email cfromm@maimonidesmed.org
Responsible Party:
Antonios Likourezos, Research Manager, Maimonides Medical Center
ClinicalTrials.gov Identifier:
NCT01914926
Other Study ID Numbers:
  • 09/01/VA02
First Posted:
Aug 2, 2013
Last Update Posted:
May 15, 2014
Last Verified:
May 1, 2014