Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial (OVID RAF)

• ClinicalTrials.gov Identifier: NCT03472495
• Recruitment Status: Completed
• First Posted: March 21, 2018
• Results First Posted: March 1, 2023
• Last Update Posted: March 1, 2023
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

Study Description

Brief Summary:

The primary objective of this study is to compare the incidence of rate control (defined as: HR <110 beats/min or conversion to sinus rhythm) at 2 hours after medication administration between oral immediate release diltiazem and intravenous continuous infusion diltiazem.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation and Flutter	Drug: Diltiazem Oral Product; Drug: Diltiazem Injectable Product	Phase 4

Detailed Description:

Atrial fibrillation (AF), a supraventricular tachyarrhythmia, is the primary diagnosis for over 467,000 hospitalizations each year. Historically, there have been two approaches to managing AF in the emergency department (ED): rate control and rhythm control.

The AFFIRM trial compared rate and rhythm control in 4,060 patients. It found no difference in mortality with the rate control approach and less hospitalizations. As a result, both rhythm and rate control are options in stable patients with an AF duration of < 48 hours. After 48 hours, rate control is preferred because of the increased risk of ischemic stroke. The subsequent RACE II trial, established that lenient heart rate control (HR <110 beats/min) was as effective as strict control (HR <80 beats/min) in preventing cardiovascular events and required less outpatient visits to achieve the goal HR. As a result of both the AFFIRM and RACE II trials, a rate control approach with a goal HR of <80-110 beats/min is the management plan for a majority of patients who present to the ED in AF. According to the American Heart Association 2014 guidelines, the initial acute, emergent management of atrial fibrillation and flutter (AFF) are similar and there are a number of medications used for rate control including beta blockers and non-dihydropyridine calcium channel blockers.

Diltiazem, a non-dihydropyridine calcium channel blocker, is often the medication of choice in the management of AFF due to its ability to be given as an intravenous (IV) push, continuous infusion, and oral (PO) immediate release or extended release tablet. In the ED, a loading dose of IV diltiazem 0.25 mg/kg is usually administered to obtain a heart rate of < 110 beats/min or a decrease of at least 20% in the ventricular rate. If this does not work then a second bolus of 0.35mg/kg is administered. Once rate control of <110 beats/min or a 20% decrease in ventricular rate is obtained physicians typically chose between oral immediate release diltiazem tablet or IV continuous infusion diltiazem to maintain heart rate control. Both options allow for dose changes in the short term. The oral immediate release diltiazem tablet has a fast onset of action of 30-60 minutes and is dosed every 6 hours. Intravenous continuous infusion diltiazem has a variable onset of action with a titration frequency of every 15-30 minutes. The use of oral diltiazem allows for possible placement on a monitored general floor bed, whereas an intravenous drip requires placement to step down or intensive level of care. This impacts bed status and length of stay in the emergency department. Both oral and intravenous diltiazem are used clinically; however, no prospective studies exist comparing the two strategies. Retrospective data suggests that both forms are equal in their ability to control heart rate.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial
• Actual Study Start Date: June 1, 2018
• Actual Primary Completion Date: March 21, 2021
• Actual Study Completion Date: March 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Oral Immediate Release Diltiazem; Diltiazem immediate release 60mg orally once (Diltiazem oral product)	Drug: Diltiazem Oral Product; Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is <60 kg)
Active Comparator: Continuous Infusion IV Diltiazem; Diltiazem 2.5-5 mg/hour intravenous Titrate by 1.25 mg every 15-60 minutes. Maximum titration dose 15 mg/hour. Titration Goal of HR <110 (Diltiazem Injectable Product)	Drug: Diltiazem Injectable Product; Diltiazem Continuous Infusion Titrated

Outcome Measures

Primary Outcome Measures :

1. Heart Rate Control [ Time Frame: 2 hrs ]
   Number of participant achieving heart rate control (defined as: HR <110 beats/min or conversion to sinus rhythm) at 2 hours after medication administration between oral immediate release and intravenous continuous infusion diltiazem

Secondary Outcome Measures :

1. Adverse Event Rate [ Time Frame: 4 hrs ]
   Number of participants with heart rate or blood pressure adverse events: Heart rate < 60 beats/min, or systolic blood pressure <90 mmHg requiring intervention (intravenous fluid bolus, vasopressors, medication discontinuation)

Other Outcome Measures:

1. Participant Specific Variables Associated With Heart Rate Control in Each Treatment Arm [ Time Frame: 4 hrs ]
   These variables include: Age, sex, race, weight, history of atrial fibrillation or flutter, history of hypertension, history of congestive heart failure, prior medication therapy, mean initial HR, duration of atrial fibrillation or flutter episode (<48 hrs or >48 hrs), mean initial diltiazem dose (mg/kg)

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• >/= 18 years old
• Atrial fibrillation or flutter on electrocardiogram
• Heart rate >110 beats/min
• Systolic blood pressure >/= 90 mmHg

Exclusion Criteria:

• Limited English proficiency (LEP)
• Pregnant
• Prisoners
• Wolff Parkinson White syndrome
• Administration of electrical or chemical cardioversion before screening
• Administration of other antiarrhythmics for acute heart rate control (excluding adenosine)
• History of allergy or idiosyncratic reaction to diltiazem
• Unable to take oral medications
• Heart rate <60 beats/min

Contacts and Locations

Locations

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Virginia Commonwealth University

Investigators

• Principal Investigator: Tammy T Nguyen, PharmD, BCPS; Virginia Commonwealth University

  Study Documents (Full-Text)

Documents provided by Virginia Commonwealth University:

Study Protocol and Statistical Analysis Plan  [PDF] January 3, 2018

More Information

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT03472495
• Other Study ID Numbers: HM20009559
• First Posted: March 21, 2018
• Results First Posted: March 1, 2023
• Last Update Posted: March 1, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Virginia Commonwealth University:

Diltiazem; Atrial Fibrillation; Atrial Flutter; Emergency Medicine

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Diltiazem; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents