Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control

NCT02025465 | Unknown Phase 4

• 1 other identifier: 1997386
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 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. 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.

Conditions

Atrial Fibrillation; Atrial Flutter

Keywords

Atrial Fibrillation; Atrial Flutter; Metoprolol; Diltiazem

Outcome Measures

Primary Outcomes (8)

• Conversion to sinus rhythm

  Conversion to sinus rhythm

  2 hours

• Conversion to sinus rhythm

  Conversion to sinus rhythm

  4 hours

• Conversion to sinus rhythm

  Conversion to sinus rhythm

  6 hours

• Conversion to sinus rhythm

  Conversion to sinus rhythm

  8 hours

• Heart rate control

  Heart rate control

  2 hours

• Heart rate control

  Heart rate control

  4 hours

• Heart rate control

  Heart rate control

  6 hours

• Heart rate control

  Heart rate control

  8 hours

Secondary Outcomes (3)

• Home discharges from Emergency Department (ED)

  Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.

• Total hospital cost

  Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.

• Rehospitalization for Atrial Fibrillation

  Up to 6 months post discharge

Study Arms (2)

Metoprolol

EXPERIMENTAL

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

Diltiazem

ACTIVE COMPARATOR

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

Interventions

Metoprolol DRUG

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.

Also known as: Lopressor

Metoprolol

Diltiazem DRUG

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.

Also known as: Cardizem

Diltiazem

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• CAMC Health System: lead

Study Sites (1)

Charleston Area Medical Center

Charleston, West Virginia, 25304, United States

RECRUITING

Related Publications (10)

• Wong CX, Brooks AG, Leong DP, Roberts-Thomson KC, Sanders P. The increasing burden of atrial fibrillation compared with heart failure and myocardial infarction: a 15-year study of all hospitalizations in Australia. Arch Intern Med. 2012 May 14;172(9):739-41. doi: 10.1001/archinternmed.2012.878. No abstract available.

  PMID: 22782205 BACKGROUND

• Wolowacz SE, Samuel M, Brennan VK, Jasso-Mosqueda JG, Van Gelder IC. The cost of illness of atrial fibrillation: a systematic review of the recent literature. Europace. 2011 Oct;13(10):1375-85. doi: 10.1093/europace/eur194. Epub 2011 Jul 14.

  PMID: 21757483 BACKGROUND

• Stiell IG, Macle L; CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: management of recent-onset atrial fibrillation and flutter in the emergency department. Can J Cardiol. 2011 Jan-Feb;27(1):38-46. doi: 10.1016/j.cjca.2010.11.014.

  PMID: 21329861 BACKGROUND

• Lip GY, Huber K, Andreotti F, Arnesen H, Airaksinen JK, Cuisset T, Kirchhof P, Marin F; Consensus Document of European Society of Cardiology Working Group on Thrombosis. Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary--a Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2010 Jun;31(11):1311-8. doi: 10.1093/eurheartj/ehq117. Epub 2010 May 6.

  PMID: 20447945 BACKGROUND

• Fuster V, Ryden 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. No abstract available.

  PMID: 21382897 BACKGROUND

• Demircan C, Cikriklar HI, Engindeniz Z, Cebicci H, Atar N, Guler V, Unlu EO, Ozdemir B. Comparison of the effectiveness of intravenous diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation. Emerg Med J. 2005 Jun;22(6):411-4. doi: 10.1136/emj.2003.012047.

  PMID: 15911947 BACKGROUND

• 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

  BACKGROUND

• Hilleman DE, Reyes AP, Mooss AN, Packard KA. Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery. Curr Med Res Opin. 2003;19(5):376-82. doi: 10.1185/030079903125001929.

  PMID: 13678474 BACKGROUND

• Hassan S, Slim AM, Kamalakannan D, Khoury R, Kakish E, Maria V, Ahmed S, Pires LA, Kronick SL, Oral H, Morady F. Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison. J Cardiovasc Pharmacol Ther. 2007 Sep;12(3):227-31. doi: 10.1177/1074248407303792.

  PMID: 17875950 BACKGROUND

• Kuhlkamp V, Schirdewan A, Stangl K, Homberg M, Ploch M, Beck OA. Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2000 Jul;36(1):139-46. doi: 10.1016/s0735-1097(00)00693-8.

  PMID: 10898425 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter

Interventions

Metoprolol; Diltiazem

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• William H. Carter, MD

  West Virginia University - Charleston Division/CAMC

  PRINCIPAL INVESTIGATOR

• Bill Payne, MD

  West Virginia University - Charleston Division/CAMC

  STUDY DIRECTOR

Central Study Contacts

Alfred Tager

CONTACT

304-388-9920; alfred.tager@camc.org

Maher Kali, MD

CONTACT

304-388-9909; maher.kali@camc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine - West Virginia University

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: January 1, 2014
• Study Start: December 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 9, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)