Atrial FibrillationPhase 4NCT02025465
Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control
A Phase 4 study testing Metoprolol and Diltiazem in people with Atrial Fibrillation and Atrial Flutter, run by CAMC Health System at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Atrial Flutter
- What is being tested?
- Metoprolol and Diltiazem
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to 30 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 20Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Charleston Area Medical Center
Charleston, West Virginia, 25304
About this study
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.
Read more
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:
- 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).
- 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.
- 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).
- 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).
- 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.
Read the detailed description
If either an initial DT or MET strategy are shown to be more effective in obtaining rate and rhythm control, decreasing length of stay in the ED, and decreasing admissions and readmissions, there is a potential for: 1.) Major health cost savings; 2.) Improved bed utilization for our hospital, which is frequently at capacity and unable to accept transfers from outlying hospitals; and, 3.) Education of ED and non-ED health care providers of optimal AF/FL medication options.
Sample
Preliminary information obtained from CAMC's Data Warehouse from July 1, 2011 to June 30, 2012 revealed 370 patients were seen in the Emergency Department (ED) at either CAMC Memorial or General Hospitals with a diagnosis of AF/FL, without any other acute co-morbidity. The investigators will identify which Hospital the patient was enrolled.
The investigators will enroll a total of 150 patients based on the following:
Prior data indicate that the conversion to a normal sinus rhythm by 8 hours is approximately 20%. If the investigators wish to detect a 25% change between medications then the investigators would need to include a total of 150 patients (75 in each cohort) to reject the null hypothesis that the conversion rates are equal between the 2 medications with probability (power) 0.8 and Type I error < 0.05. The investigators will use a continuity-corrected chi-squared statistic or Fisher's exact test to test our hypothesis. Power analysis performed using GPower Version 3.
Procedures
Potential study patients will be identified by an ED nurse or a member of the study team using the inclusion and exclusion criteria. ED nurses will be informed of the study by charge nurses who have been educated about the protocol by the research team. The purpose, content and logistics of the study will also be described to ED physicians participating in the study. Research assistants, when available, will be notified by cell phone or pager to see patient in the ED within 20 minutes. The attending physician or resident will be informed of the potential study patient. The attending physician or resident will give the research associate/member of the study team permission to discuss the study with the patient. If the patient is interested in participating in the study, the research associate/member of the study team will discuss the details of the study and review the consent form. It is likely the onset of treatment with DT or MET will be delayed 30 to 40 minutes due to the consenting process and study enrollment. The attending physician must agree to this delay.
At this point the attending physician will discuss the study with the patient and answer questions. The physicians or resident initially talking with the patients about being in the trial will have Collaborative Institutional Training Initiative (CITI) training. General education to the ED staff will be made concerning aims and objectives of the strategy study. If the patient is still interested and willing to participate, the informed consent and Health Insurance Portability and Accountability Act (HIPAA) privacy statement will be signed.
Following consent, patients will be randomized to either IV diltiazem (DT) or IV metoprolol (MET). Sealed envelopes containing the randomized treatment protocol will be maintained on the ED premises to be pulled consecutively after a patient has been consented to be in the study. Inside the envelope, the specific treatment plan will be revealed. Treatment with either DT or MET will be initiated using standard CAMC protocol. Deviations from the randomly assigned medication regimen would be at the attending physician's discretion pending vital signs response. If the study drug is stopped or changed to a different type of medication, the patient's participation will continue and medications will be documented with the analysis of results being the intent to treat.
The same physicians rotate at both General and Memorial Hospitals. The investigators will start at the Memorial Hospital, but after experience with enrollment the investigators may enroll patients from both Hospitals.
Data Analysis
Basic descriptive statistics including means and standard deviations for continuous variables and proportions and frequencies for categorical variables will be used to describe the patient sample and disease characteristics.
To determine if a medication regimen (MET vs DT) is noted by descriptive analysis to be associated with primary aim 1 for treating AF/FL in the ED or during hospitalization (Primary Aim-1), the investigators will describe the proportion of patients with rhythm control (defined as normal sinus rhythm) by time of ED discharge using Chi-square analysis with continuity correction. Using the same statistical tests, the investigators will describe the proportion of patients with normal sinus rhythm at time of hospital discharge, in patients admitted to CAMC. Possible confounders, including patient characteristics, co-morbid conditions, ED events, or deviation from medicine regimen on achieving NSR will be examined by comparing patients with the confounder to those without the confounder of interest using Chi-square with continuity correction analyses if data is categorical, t-test or Mann-Whitney U analysis if data is continuous. In addition, the investigators will examine the effect of medication regimen on rate control (defined as heart rate < 100 bpm) (Primary Aim-2) at 2, 4, 6, 8 hours in the identical manner as described for rhythm control including the examination of confounding variables.
The proportion of patients receiving CAMC hospital admission versus discharged to home from the ED will be described between the two medication regimens using Chi-square analysis with continuity correction to determine if one regimen resulted in a greater percentage of home discharges directly from the ED (Secondary Aim-1). The effect of possible confounders including patient characteristics, ED events, achieving rate and/or rhythm control in the ED or deviation from medication regimen will be examined by describing patients with the confounder to those without the confounder of interest on the need for hospital admission using Chi-square with continuity correction analyses if data is categorical, t-test or Mann-Whitney U analysis, if data is continuous. Those confounders that are shown to associate with ED discharge to home will be included in a multivariate analysis (binomial logistic regression) to examine if medication regimen associates with ED discharge to home in the presence of confounders.
To determine if a medication regimen (MET vs DT) associated with decreased financial costs (Secondary Aim-2), ED costs will be examined between the 2 medication regimens in all patients using t-tests, or Mann-Whitney U analysis. In addition, the total cost of hospitalization (ED + hospital costs) of patients admitted to the CAMC hospital from the ED will be examined between the medication regimens. Cost will also be examined in relationship to length of stay by examining cost /length of stay between the two treatment groups using the same statistical tests.
The need for readmission and atrial fibrillation reoccurrence as reported by the phone questionnaire (Secondary Aim-3) will be compared between the two medication regimens using Chi-square with continuity correction analyses. The investigators will also determine which rate control medication at time of phone interview associates with freedom from atrial fibrillation reoccurrence using chi-square analysis. Lastly, the time between discharge and phone survey study completion (maximum: 6 months) will be determined and the investigators will examine the effect of this lag time (4- 6 months) on the percentage of patients requiring readmission and/or having a reoccurrence of atrial fibrillation via chi square analysis.
For all applicable analyses described above, Fisher's exact tests will be substituted for Chi square analysis when appropriate. For all comparisons, a p level of < 0.05 will be used to determine statistical significance. The statistical package Statistical Analysis Software (SAS) (Version 9.3) will be used to analyze data.
Confidentiality
Minimal patient identification information will be collected. The patient account number and telephone number must be collected. Subjects will also be assigned a study number for data analysis; account numbers will not be included in the data analysis. Personal health information will be available only to the study investigators. All collected data will be stored in a locked filing cabinet in the Emergency Department until it can be delivered to CAMC Outcomes Research. Electronic data will be stored on a password protected computer. At the conclusion of the study, all data collection sheets will be shredded and electronic data destroyed.
- Conditions
- Atrial Fibrillation, Atrial Flutter
- Being tested
- Metoprolol, Diltiazem
- Keywords
- Atrial Fibrillation, Atrial Flutter, Metoprolol, Diltiazem
- Medical subject headings
- Atrial Fibrillation, Atrial Flutter
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetoprololDrug
Also called Lopressor
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.
DiltiazemDrug
Also called Cardizem
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Diltiazem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion to sinus rhythm
Conversion to sinus rhythm
Measured: 2 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Measured: 4 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Measured: 6 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Measured: 8 hours
Heart rate control
Heart rate control
Measured: 2 hours
Heart rate control
Heart rate control
Measured: 4 hours
Heart rate control
Heart rate control
Measured: 6 hours
Heart rate control
Heart rate control
Measured: 8 hours
Secondary outcomes (3)
Home discharges from Emergency Department (ED)
Home discharges from Emergency Department (ED)
Measured: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.
Total hospital cost
Total costs during the time in the ED plus any in hospital costs that might have occurred.
Measured: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.
Rehospitalization for Atrial Fibrillation
Rehospitalization for Atrial Fibrillation
Measured: Up to 6 months post discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2014 (estimated)
- Study startDec 2013
- Primary completion12 Feb 2023
- Study completion30 May 2024
Why it stopped: Low enrollment and PI retired.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- CAMC Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William H. Carter, MD, Principal investigator, West Virginia University - Charleston Division/CAMCBill Payne, MD, Study director, West Virginia University - Charleston Division/CAMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02025465
- Sponsor's protocol ID
- 1997386
- Status last verified
- May 2024
- First submitted
- 16 Dec 2013
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22782205Wolowacz 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.
PubMed 21757483Stiell 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.
PubMed 21329861Lip 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.
PubMed 20447945Fuster 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.
PubMed 21382897Demircan 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.
PubMed 15911947Diao, 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
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.
PubMed 13678474Hassan 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.
PubMed 17875950Kuhlkamp 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.
PubMed 10898425
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control
- ClinicalTrials.gov ID
- NCT02025465
- Acronym / sponsor ID
- 1997386
- Conditions
- Atrial Fibrillation, Atrial Flutter
- Keywords
- Atrial Fibrillation, Atrial Flutter, Metoprolol, Diltiazem
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment and PI retired.
- Enrolment
- 69 participants (actual)
- Lead sponsor
- CAMC Health SystemUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- 12 Feb 2023 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 1 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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).
- 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.
- 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).
- 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).
- 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.
Detailed description
If either an initial DT or MET strategy are shown to be more effective in obtaining rate and rhythm control, decreasing length of stay in the ED, and decreasing admissions and readmissions, there is a potential for: 1.) Major health cost savings; 2.) Improved bed utilization for our hospital, which is frequently at capacity and unable to accept transfers from outlying hospitals; and, 3.) Education of ED and non-ED health care providers of optimal AF/FL medication options.
Sample
Preliminary information obtained from CAMC's Data Warehouse from July 1, 2011 to June 30, 2012 revealed 370 patients were seen in the Emergency Department (ED) at either CAMC Memorial or General Hospitals with a diagnosis of AF/FL, without any other acute co-morbidity. The investigators will identify which Hospital the patient was enrolled.
The investigators will enroll a total of 150 patients based on the following:
Prior data indicate that the conversion to a normal sinus rhythm by 8 hours is approximately 20%. If the investigators wish to detect a 25% change between medications then the investigators would need to include a total of 150 patients (75 in each cohort) to reject the null hypothesis that the conversion rates are equal between the 2 medications with probability (power) 0.8 and Type I error < 0.05. The investigators will use a continuity-corrected chi-squared statistic or Fisher's exact test to test our hypothesis. Power analysis performed using GPower Version 3.
Procedures
Potential study patients will be identified by an ED nurse or a member of the study team using the inclusion and exclusion criteria. ED nurses will be informed of the study by charge nurses who have been educated about the protocol by the research team. The purpose, content and logistics of the study will also be described to ED physicians participating in the study. Research assistants, when available, will be notified by cell phone or pager to see patient in the ED within 20 minutes. The attending physician or resident will be informed of the potential study patient. The attending physician or resident will give the research associate/member of the study team permission to discuss the study with the patient. If the patient is interested in participating in the study, the research associate/member of the study team will discuss the details of the study and review the consent form. It is likely the onset of treatment with DT or MET will be delayed 30 to 40 minutes due to the consenting process and study enrollment. The attending physician must agree to this delay.
At this point the attending physician will discuss the study with the patient and answer questions. The physicians or resident initially talking with the patients about being in the trial will have Collaborative Institutional Training Initiative (CITI) training. General education to the ED staff will be made concerning aims and objectives of the strategy study. If the patient is still interested and willing to participate, the informed consent and Health Insurance Portability and Accountability Act (HIPAA) privacy statement will be signed.
Following consent, patients will be randomized to either IV diltiazem (DT) or IV metoprolol (MET). Sealed envelopes containing the randomized treatment protocol will be maintained on the ED premises to be pulled consecutively after a patient has been consented to be in the study. Inside the envelope, the specific treatment plan will be revealed. Treatment with either DT or MET will be initiated using standard CAMC protocol. Deviations from the randomly assigned medication regimen would be at the attending physician's discretion pending vital signs response. If the study drug is stopped or changed to a different type of medication, the patient's participation will continue and medications will be documented with the analysis of results being the intent to treat.
The same physicians rotate at both General and Memorial Hospitals. The investigators will start at the Memorial Hospital, but after experience with enrollment the investigators may enroll patients from both Hospitals.
Data Analysis
Basic descriptive statistics including means and standard deviations for continuous variables and proportions and frequencies for categorical variables will be used to describe the patient sample and disease characteristics.
To determine if a medication regimen (MET vs DT) is noted by descriptive analysis to be associated with primary aim 1 for treating AF/FL in the ED or during hospitalization (Primary Aim-1), the investigators will describe the proportion of patients with rhythm control (defined as normal sinus rhythm) by time of ED discharge using Chi-square analysis with continuity correction. Using the same statistical tests, the investigators will describe the proportion of patients with normal sinus rhythm at time of hospital discharge, in patients admitted to CAMC. Possible confounders, including patient characteristics, co-morbid conditions, ED events, or deviation from medicine regimen on achieving NSR will be examined by comparing patients with the confounder to those without the confounder of interest using Chi-square with continuity correction analyses if data is categorical, t-test or Mann-Whitney U analysis if data is continuous. In addition, the investigators will examine the effect of medication regimen on rate control (defined as heart rate < 100 bpm) (Primary Aim-2) at 2, 4, 6, 8 hours in the identical manner as described for rhythm control including the examination of confounding variables.
The proportion of patients receiving CAMC hospital admission versus discharged to home from the ED will be described between the two medication regimens using Chi-square analysis with continuity correction to determine if one regimen resulted in a greater percentage of home discharges directly from the ED (Secondary Aim-1). The effect of possible confounders including patient characteristics, ED events, achieving rate and/or rhythm control in the ED or deviation from medication regimen will be examined by describing patients with the confounder to those without the confounder of interest on the need for hospital admission using Chi-square with continuity correction analyses if data is categorical, t-test or Mann-Whitney U analysis, if data is continuous. Those confounders that are shown to associate with ED discharge to home will be included in a multivariate analysis (binomial logistic regression) to examine if medication regimen associates with ED discharge to home in the presence of confounders.
To determine if a medication regimen (MET vs DT) associated with decreased financial costs (Secondary Aim-2), ED costs will be examined between the 2 medication regimens in all patients using t-tests, or Mann-Whitney U analysis. In addition, the total cost of hospitalization (ED + hospital costs) of patients admitted to the CAMC hospital from the ED will be examined between the medication regimens. Cost will also be examined in relationship to length of stay by examining cost /length of stay between the two treatment groups using the same statistical tests.
The need for readmission and atrial fibrillation reoccurrence as reported by the phone questionnaire (Secondary Aim-3) will be compared between the two medication regimens using Chi-square with continuity correction analyses. The investigators will also determine which rate control medication at time of phone interview associates with freedom from atrial fibrillation reoccurrence using chi-square analysis. Lastly, the time between discharge and phone survey study completion (maximum: 6 months) will be determined and the investigators will examine the effect of this lag time (4- 6 months) on the percentage of patients requiring readmission and/or having a reoccurrence of atrial fibrillation via chi square analysis.
For all applicable analyses described above, Fisher's exact tests will be substituted for Chi square analysis when appropriate. For all comparisons, a p level of < 0.05 will be used to determine statistical significance. The statistical package Statistical Analysis Software (SAS) (Version 9.3) will be used to analyze data.
Confidentiality
Minimal patient identification information will be collected. The patient account number and telephone number must be collected. Subjects will also be assigned a study number for data analysis; account numbers will not be included in the data analysis. Personal health information will be available only to the study investigators. All collected data will be stored in a locked filing cabinet in the Emergency Department until it can be delivered to CAMC Outcomes Research. Electronic data will be stored on a password protected computer. At the conclusion of the study, all data collection sheets will be shredded and electronic data destroyed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol | Experimental | Drug: MetoprololMetoprolol 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 |
| Diltiazem | Active comparator | Drug: DiltiazemBolus 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetoprololAlso: LopressorThe 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. | Drug | Metoprolol |
| DiltiazemAlso: CardizemThe 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. | Drug | Diltiazem |
Primary outcome
Conversion to sinus rhythm
Time frame: 2 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Time frame: 4 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Time frame: 6 hours
Conversion to sinus rhythm
Conversion to sinus rhythm
Time frame: 8 hours
Conversion to sinus rhythm
Heart rate control
Time frame: 2 hours
Heart rate control
Heart rate control
Time frame: 4 hours
Heart rate control
Heart rate control
Time frame: 6 hours
Heart rate control
Heart rate control
Time frame: 8 hours
Heart rate control
3 secondary outcomes
Home discharges from Emergency Department (ED)
Time frame: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.
Total hospital cost
Time frame: Date of admission to ED and duration of hospital stay, an expected average of 5 weeks.
Rehospitalization for Atrial Fibrillation
Time frame: Up to 6 months post discharge
Results and safety
The study was stopped early (reason given: Low enrollment and PI retired.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Background: PubMed 22782205Wong 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.
- Background: PubMed 21757483Wolowacz 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.
- Background: PubMed 21329861Stiell 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.
- Background: PubMed 20447945Lip 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.
- Background: PubMed 21382897Fuster 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.
- Background: PubMed 15911947Demircan 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.
- BackgroundDiao, 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: PubMed 13678474Hilleman 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.
- Background: PubMed 17875950Hassan 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.
- Background: PubMed 10898425Kuhlkamp 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William H. Carter, MD principal investigator
West Virginia University - Charleston Division/CAMC
Bill Payne, MD study director
West Virginia University - Charleston Division/CAMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metoprolol and Diltiazem in people with Atrial Fibrillation and Atrial Flutter, run by CAMC Health System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low enrollment and PI retired.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion to sinus rhythm (time frame: 2 hours). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02025465, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.