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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral Immediate Release Diltiazem | Active Comparator | Diltiazem immediate release 60mg orally once (Diltiazem oral product) |
|
| Continuous Infusion IV Diltiazem | Active Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Diltiazem Oral Product | Drug | Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is <60 kg) |
|
| 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 |
| 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 |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tammy T Nguyen, PharmD, BCPS | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Continuous Infusion IV Diltiazem |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 2 hrs |
|
4 hours
self report by participant Only bradycardia (HR <60 beats/min) or hypotension (SBP <90 mmHg requiring intervention including IVF bolus administration, vasopressors, or medication discontinuation) related adverse events were recorded.
Mortality was not recorded Non-serious adverse events were not recorded
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tammy Nguyen, PharmD | Virginia Commonwealth University | 8046630969 | Tammy.Nguyen@vcuhealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 3, 2018 | Feb 1, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D001282 | Atrial Flutter |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| Diltiazem Injectable Product | Drug | Diltiazem Continuous Infusion Titrated |
|
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 |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | 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) | Posted | Count of Participants | Participants | 4 hrs |
|
|
|
| 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) | Not Posted | 4 hrs | Participants |
| 0 |
| 0 |
| 1 |
| 8 |
| 0 |
| 0 |
| EG001 | 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 | 0 | 0 | 0 | 6 | 0 | 0 |
| Braydcardia | Cardiac disorders | Non-systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |