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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation and Flutter
• Intervention / Treatment: Drug: Diltiazem Oral Product; Drug: Diltiazem Injectable Product

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate Control	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	2 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event Rate	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)	4 hrs

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Specific Variables Associated With Heart Rate Control in Each Treatment Arm	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)	4 hrs

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): March 21, 2021
• Study Completion (Actual): March 21, 2021

Study Registration Dates

• First Submitted: February 23, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Emergency Medicine; Atrial Flutter; Diltiazem
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Diltiazem
• Other Study ID Numbers: HM20009559

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No