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Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial

Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03472495
Acronym
OVID RAF
Enrollment
19
Registered
2018-03-21
Start date
2018-06-01
Completion date
2021-03-21
Last updated
2023-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atrial Fibrillation and Flutter

Keywords

Diltiazem, Atrial Fibrillation, Atrial Flutter, Emergency Medicine

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.

Interventions

DRUGDiltiazem Oral Product

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

DRUGDiltiazem Injectable Product

Diltiazem Continuous Infusion Titrated

Sponsors

Virginia Commonwealth University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Heart Rate Control2 hrsNumber 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

MeasureTime frameDescription
Adverse Event Rate4 hrsNumber 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

MeasureTime frameDescription
Participant Specific Variables Associated With Heart Rate Control in Each Treatment Arm4 hrsThese 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)

Countries

United States

Participant flow

Participants by arm

ArmCount
Oral Immediate Release Diltiazem
Diltiazem immediate release 60mg orally once (Diltiazem oral product) Diltiazem Oral Product: Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is \<60 kg)
9
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) Diltiazem Injectable Product: Diltiazem Continuous Infusion Titrated
10
Total19

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyPhysician Decision02
Overall StudyTreatment no longer indicated12

Baseline characteristics

CharacteristicOral Immediate Release DiltiazemTotalContinuous Infusion IV Diltiazem
Age, Continuous61.7 Years
STANDARD_DEVIATION 11.6
59.9 Years
STANDARD_DEVIATION 10.6
58.3 Years
STANDARD_DEVIATION 9.9
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
9 Participants19 Participants10 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
4 Participants10 Participants6 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants9 Participants4 Participants
Region of Enrollment
United States
9 participants19 participants10 participants
Sex: Female, Male
Female
4 Participants10 Participants6 Participants
Sex: Female, Male
Male
5 Participants9 Participants4 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 00 / 0
other
Total, other adverse events
0 / 00 / 0
serious
Total, serious adverse events
1 / 80 / 6

Outcome results

Primary

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

Time frame: 2 hrs

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Oral Immediate Release DiltiazemHeart Rate Control8 Participants
Continuous Infusion IV DiltiazemHeart Rate Control4 Participants
Secondary

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)

Time frame: 4 hrs

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Oral Immediate Release DiltiazemAdverse Event Rate1 Participants
Continuous Infusion IV DiltiazemAdverse Event Rate0 Participants
Other Pre-specified

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)

Time frame: 4 hrs

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026