Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial

NCT ID: NCT03472495

Last Updated: 2023-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-01
• Study Completion Date: 2021-03-21

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.

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.

Conditions

Atrial Fibrillation and Flutter

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral Immediate Release Diltiazem

Diltiazem immediate release 60mg orally once (Diltiazem oral product)

Group Type: ACTIVE_COMPARATOR

Diltiazem Oral Product

Intervention Type: DRUG

Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is \<60 kg)

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)

Group Type: ACTIVE_COMPARATOR

Diltiazem Injectable Product

Intervention Type: DRUG

Diltiazem Continuous Infusion Titrated

Interventions

Diltiazem Oral Product

Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is \<60 kg)

Intervention Type: DRUG

Diltiazem Injectable Product

Diltiazem Continuous Infusion Titrated

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tammy T Nguyen, PharmD, BCPS

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HM20009559

Identifier Type: -

Identifier Source: org_study_id