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Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control

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ClinicalTrials.gov Identifier: NCT02025465
Recruitment Status : Unknown
Verified August 2017 by William Carter, CAMC Health System.
Recruitment status was:  Recruiting
First Posted : January 1, 2014
Last Update Posted : August 9, 2017
Sponsor:
Information provided by (Responsible Party):
William Carter, CAMC Health System

Brief Summary:

Atrial Fibrillation and atrial flutter (AF/FL) is the usually irregular beating of the heart and is a rapidly growing cause of hospitalization. Between 1993 to 2007 AF/FL hospitalizations have increased 203% compared to a 71% increase for all hospitalizations. Changing procedure management such as ablation, transesophageal have had a minimal impact on the trends and there is a need to evaluate Emergency Department (ED) management options of AF/FL that may decrease hospitalizations.

The most commonly used medications to control heart rate are metoprolol (MET), a beta blocker, or diltiazem (DT), a calcium channel blocker. Beta blockers are medications that cause the heart to beat more slowly and with less force. DT also helps blood vessels open up to improve blood flow. Both DT and MET are used alone or together with other medicines to treat severe chest pain (angina), high blood pressure (hypertension) or rapid heartbeat. Both are equally acceptable according to recent guidelines for AF/FL. There are limited studies comparing MET to DT for rate control for AF/FL.

The initial goal for AF/FL management in the Emergency Department is usually rate control.

The most commonly used rate control medications are metoprolol (MET), a beta blocker, or diltiazem (DT) a calcium blocker. Three major guidelines, including the American College of Cardiology (ACC) and the American Heart Association (AHA) indicate beta blockers and DT are equally acceptable medications for rate control in AF (3,4,5) assuming no contraindications.

There are limited studies comparing beta blockers (BB) to DT for rate control for AF:

  1. Demircan, et. al., compared bolus intravenous BB and DT in 40 patients over a 20 minute period. No follow-up information after 20 minutes was reported. No attempt was made to look at intermediate or long term results. No patients converted to normal sinus rhythm over this short treatment period and there was slightly more rate decrease at 20 minutes, with DT versus BB (6).
  2. Time from medication administration to heart rate and rhythm control. Additionally, currently guidelines consider BB or DT medications to slow AF/FL; however, there are some suggestions that BB may not only slow heart rate in AF/FL (as does DT) but also increase all AF/FL conversion from AF/FL to normal sinus rhythm(2), and aid in maintaining normal sinus rhythm (NSR) after cardioversion (10). With recent onset AF/FL occurring within 48 hours prior to the arrival to the ED, approximately 50% of AF/FL patients convert to normal rhythm spontaneously within 24 hours after arrival to the ED (6), making evaluation of current limited studies difficult. Thus, the investigators wish to examine the effect of initial medication strategy on time to NSR in a larger sample than has been previously performed.
  3. A randomized study of 48 patients in China reported significantly slower heart rate up to 20 minutes with DT 10mg IV versus metoprolol 5mg IV but not after 30 minutes (7).
  4. A retrospective study of post-operative coronary bypass patients showed the intravenous administration of the BB, esmolol, to be more effective than DT for rate control and conversion of AF/FL (8).
  5. Hassan et al reported no difference in conversion to regular rhythm with esmolol verses DT in a small, under powered, randomized study of fifty ED patients (9). Conversion to sinus rhythm occurred in 10 patients (42%) in the DT group compared with 10 patients (39%) in the esmolol group (P = 1.0). There were no statistically significant differences in heart rate between the two medications at 1, 6, 12, and 24 hours after initiation of esmolol or DT infusion.

Examples of such well quoted strategy trials are the COURAGE trial published in the New England Journal of Medicine and the PROMISE Trial, a worldwide multi-centered study that is nearing completion goal of 10,000 patients of which, Charleston Area Medical Center (CAMC) has enrolled approximately 100 patients. In this trial, patients being evaluated for chest pain will be randomized to two treatment strategies and subsequent outcomes will be recorded.

Strategy trials do not attempt to manage treatment after an initial management strategy has been determined by randomization, but, whether the initial treatment affects long-term outcomes.

This will be a prospective, randomized study comparing the outcomes of a strategy using either MET or DT in patients with AF presenting to the Charleston Area Medical Center (CAMC) ED. After presentation and receiving consent, the patient will be randomized to receive either MET or DT.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Atrial Flutter Drug: Metoprolol Drug: Diltiazem Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control
Study Start Date : December 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Metoprolol

Metoprolol 2.5 to 5.0 mg IV bolus over two minutes

Repeat every five minutes up to a total dose of 15 mg as long as tolerated (Blood pressure is over 100 mm /Hg systolic (or BP is 90 to 100 mm\Hg systolic and the patient is not dizzy))

If rate inadequate the physician has option of:

  1. Further doses of metoprolol IV or PO
  2. Intravenous amiodarone
  3. IV diltiazem
  4. Observation
Drug: Metoprolol

The attending ED physician may use higher or lower intravenous doses depending on patient response as this is the norm in clinical practice for these two medications used for decades for AF/FL rate control.

Conversion of intravenous to oral, chronic management will be left to the discretion of the ED or managing medical team.

Other Name: Lopressor

Active Comparator: Diltiazem

Bolus 0.25 Mg/Kg over two minutes (average adult dose 20 mg).

If after 15 minutes

  1. The first dose is tolerated, and
  2. Ventricular rate is over 100 beats a minute AND
  3. Blood pressure is over 100 mm /Hg systolic (or BP is 90 to 100 mm\Hg systolic and the patient is not dizzy)

Give diltiazem 0.35 Mg/Kg over two minutes (average adult dose 25 mg).

After initial bolus', start infusion 5 to 15 Mg/hour to maintain rate control as long as:

1. BP over 100 mm/Hg or between 90 and 100 mm/Hg and the patient is not dizzy.

If rate inadequate the physician has an option of:

  1. Metoprolol PO (by mouth) or IV (intravenous)
  2. Digoxin PO or IV
  3. Intravenous amiodarone
  4. Observation
Drug: Diltiazem

The attending ED physician may use higher or lower intravenous doses depending on patient response as this is the norm in clinical practice for these two medications used for decades for AF rate control.

Conversion of intravenous to oral medication for rate control for chronic management will be left to the discretion of the ED or managing medical team.

Other Name: Cardizem




Primary Outcome Measures :
  1. Conversion to sinus rhythm [ Time Frame: 2 hours ]
    Conversion to sinus rhythm

  2. Conversion to sinus rhythm [ Time Frame: 4 hours ]
    Conversion to sinus rhythm

  3. Conversion to sinus rhythm [ Time Frame: 6 hours ]
    Conversion to sinus rhythm

  4. Conversion to sinus rhythm [ Time Frame: 8 hours ]
    Conversion to sinus rhythm

  5. Heart rate control [ Time Frame: 2 hours ]
    Heart rate control

  6. Heart rate control [ Time Frame: 4 hours ]
    Heart rate control

  7. Heart rate control [ Time Frame: 6 hours ]
    Heart rate control

  8. Heart rate control [ Time Frame: 8 hours ]
    Heart rate control


Secondary Outcome Measures :
  1. Home discharges from Emergency Department (ED) [ Time Frame: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks. ]
    Home discharges from Emergency Department (ED)

  2. Total hospital cost [ Time Frame: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks. ]
    Total costs during the time in the ED plus any in hospital costs that might have occurred.

  3. Rehospitalization for Atrial Fibrillation [ Time Frame: Up to 6 months post discharge ]
    Rehospitalization for Atrial Fibrillation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients presenting to Charleston Area Medical Center (CAMC) General or Memorial Hospital ED with a primary diagnosis of AF/FL
  • Patients with a mean ventricular rate of 100 beats per minute or more within one hour of presentation

Exclusion Criteria:

  • Under age 18 years
  • A diagnosis of acute coronary syndrome (ACS) made by the admitting ED physician (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina) (beta blockers are a Class I medications for ACS)
  • Known history of heart failure with an ejection fraction <50%
  • Known ejection fraction <45%, regardless of a history of heart failure. Heart failure and a history of heart failure with an ejection fraction of 40-50% may occur with a normal ejection fraction now referred to as Heart Failure With Preserved Ejection Fraction (HFpEF) or "diastolic dysfunction". A low ejection fraction is not always associated with heart failure. Our technology of measuring ejection fraction is by no means perfect. It is acceptable to use MET in larger than usual starting doses of MET for rate control or patients with "diastolic dysfunction", but not systolic dysfunction. Thus, a patient who has an ejection fraction of 42% may possibly have an ejection fraction of 37%, possible lower. Thus the investigators want to avoid the possibility of a patient with a history of heart failure does not receive MET unless the investigators feel systolic heart failure is not present.
  • Systolic blood pressure <90 mm Hg or between 90-99 AND patient is experiencing symptoms of dizziness
  • Known allergy or adverse reactions to diltiazem or metoprolol. This is very rare.

Exclusions from ECG readings:

  • Current Atrioventricular (AV) block (2nd or 3rd degree)
  • Pre-excitation syndromes - Wolfe Parkinson White (WPW) (Accelerated AV conduction- a rare condition where MET and DT are not advised)
  • Pulse rate less 100/minute on ED admission (already at rate control)
  • Cardiogenic shock or heart failure requiring inotropic agents or intubation
  • Respiratory failure requiring intubation
  • Pregnancy or lactation (neither pregnancy or lactation are listed as definitely safe for either medication)
  • Asthma, defined as (asthma is a relative contraindication for MET:
  • current use of inhaler
  • use of steroids for dyspnea
  • history of being treated for asthma
  • Inability or unwillingness to provide informed consent
  • Physician decision
  • If either medication is a relative contraindication, the patient cannot be randomized.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02025465


Contacts
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Contact: Alfred Tager 304-388-9920 alfred.tager@camc.org
Contact: Maher Kali, MD 304-388-9909 maher.kali@camc.org

Locations
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United States, West Virginia
Charleston Area Medical Center Recruiting
Charleston, West Virginia, United States, 25304
Principal Investigator: William H. Carter, MD         
Sponsors and Collaborators
CAMC Health System
Investigators
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Principal Investigator: William H. Carter, MD West Virginia University - Charleston Division/CAMC
Study Director: Bill Payne, MD West Virginia University - Charleston Division/CAMC

Publications:
Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Kay GN, Le Huezey JY, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann LS, Smith SC Jr, Priori SG, Estes NA 3rd, Ezekowitz MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, Jacobs AK, Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Ohman EM, Stevenson WG, Tarkington LG, Yancy CW; American College of Cardiology Foundation/American Heart Association Task Force. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Mar 15;123(10):e269-367. doi: 10.1161/CIR.0b013e318214876d. Epub 2011 Mar 7.
Diao, Hong-ying; Liu, Bin; Chen, Hong-Bo; Shi, Yong-feng; Wang, Li-juan. Comparison of the effectiveness of intravenous diltiazem and metoprolol in controlling the rapid ventricular rate in patients with atrial fibrillation. Journal of Emergency Medicine 2009; Vol. 18: 1085-87

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Responsible Party: William Carter, Professor of Medicine - West Virginia University, CAMC Health System
ClinicalTrials.gov Identifier: NCT02025465     History of Changes
Other Study ID Numbers: 1997386
First Posted: January 1, 2014    Key Record Dates
Last Update Posted: August 9, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by William Carter, CAMC Health System:
Atrial Fibrillation
Atrial Flutter
Metoprolol
Diltiazem
Additional relevant MeSH terms:
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Atrial Fibrillation
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Metoprolol
Diltiazem
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents