Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial

Phase 4

Completed

• Conditions: Atrial Fibrillation and Flutter
• Interventions: Drug: Diltiazem Injectable Product; Drug: Diltiazem Oral Product

• Registration Number: NCT03472495
• Lead Sponsor: Virginia Commonwealth University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-02-23
• Study First Submitted QC: 2018-03-20
• Study First Posted: 2018-03-21
• Study Start: 2018-06-01
• Primary Completion: 2021-03-21
• Study Completion: 2021-03-21
• Status Verified: 2023-02
• Results First Submitted: 2023-02-03
• Results First Submitted QC: 2023-02-03
• Last Update Submitted: 2023-02-03
• Results First Posted: 2023-03-01
• Last Update Posted: 2023-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Continuous Infusion IV Diltiazem	Diltiazem Injectable Product	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)
Oral Immediate Release Diltiazem	Diltiazem Oral Product	Diltiazem immediate release 60mg orally once (Diltiazem oral product)

Primary Outcome Measures

Name	Time	Method
Heart Rate Control	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

Name	Time	Method
Adverse Event Rate	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)

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States