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

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

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01914926
Acronym
DiME
Enrollment
54
Registered
2013-08-02
Start date
2009-06-30
Completion date
2010-11-30
Last updated
2014-05-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Rate and Rhythm Disorders

Keywords

metoprolol, diltiazem, heart rate

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.

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.

Interventions

DRUGMetoprolol
DRUGDiltiazem

Sponsors

Antonios Likourezos
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
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.

Design outcomes

Primary

MeasureTime frameDescription
Percent of Patients Reaching Target HR<100bpm Within 30 Minutes30 minutesPercent of patient who reached a HR\<100bpm within 30 minutes from baseline.

Countries

United States

Participant flow

Recruitment details

Recruitment of patients was from June 2009 to November 2010

Pre-assignment details

No significant events

Participants by arm

ArmCount
Metoprolol Study Group
Patients Receiving metoprolol administered at a dose of 0.15 mg/kg (to a maximum dose of 10 mg)
29
Diltiazem Study Group
Patients receiving diltiazem administered parenterally at a dose of 0.25 mg/kg (to a maximum dose of 30 mg)
25
Total54

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event10
Overall Studyuncooperative, agitated and removed01

Baseline characteristics

CharacteristicDiltiazem Study GroupMetoprolol Study GroupTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
12 Participants18 Participants30 Participants
Age, Categorical
Between 18 and 65 years
13 Participants11 Participants24 Participants
Age, Continuous65.85 years
STANDARD_DEVIATION 13.22
68.95 years
STANDARD_DEVIATION 14.94
67.52 years
STANDARD_DEVIATION 14.12
Region of Enrollment
United States
25 participants29 participants54 participants
Sex: Female, Male
Female
15 Participants17 Participants32 Participants
Sex: Female, Male
Male
10 Participants12 Participants22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 290 / 25
serious
Total, serious adverse events
0 / 290 / 25

Outcome results

Primary

Percent of Patients Reaching Target HR<100bpm Within 30 Minutes

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

Time frame: 30 minutes

ArmMeasureValue (NUMBER)
Metoprolol Study GroupPercent of Patients Reaching Target HR<100bpm Within 30 Minutes46.4 percentage of participants
Diltiazem Study GroupPercent of Patients Reaching Target HR<100bpm Within 30 Minutes95.8 percentage of participants
Comparison: 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.p-value: 0.0001Chi-squared

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026