Atrial Fibrillation and FlutterPhase 4OVID RAFNCT03472495
Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial
A Phase 4 study testing Diltiazem Oral Product and Diltiazem Injectable Product in people with Atrial Fibrillation and Flutter, run by Virginia Commonwealth University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation and Flutter
- What is being tested?
- Diltiazem Oral Product and Diltiazem Injectable Product
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2018to 21 Mar 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >/= 18 years old
- Atrial fibrillation or flutter on electrocardiogram
- Heart rate >110 beats/min
- Systolic blood pressure >/= 90 mmHg
Who cannot join
- 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)
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- History of allergy or idiosyncratic reaction to diltiazem
- Unable to take oral medications
- Heart rate <60 beats/min
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
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.
Read the 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
- Being tested
- Diltiazem Oral Product, Diltiazem Injectable Product
- Keywords
- Diltiazem, Atrial Fibrillation, Atrial Flutter, Emergency Medicine
- Medical subject headings
- Atrial Fibrillation, Atrial Flutter
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diltiazem Oral ProductDrug
Diltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is <60 kg)
Diltiazem Injectable ProductDrug
Diltiazem Continuous Infusion Titrated
| Study group | Role | What they receive |
|---|---|---|
| Oral Immediate Release Diltiazem | Active comparator | Diltiazem immediate release 60mg orally once (Diltiazem oral product) Receives: Drug: 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) Receives: Drug: Diltiazem Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 hrs
Secondary outcomes (1)
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)
Measured: 4 hrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2018
- Study start1 Jun 2018
- Primary completion21 Mar 2021
- Study completion21 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atrial Fibrillation and FlutterStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tammy T Nguyen, PharmD, BCPS, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03472495
- Sponsor's protocol ID
- HM20009559
- Acronym
- OVID RAF
- Status last verified
- Feb 2023
- First submitted
- 23 Feb 2018
- Last updated
- 1 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral vs Intravenous Diltiazem for Rapid Atrial Fibrillation/Flutter Trial
- ClinicalTrials.gov ID
- NCT03472495
- Acronym / sponsor ID
- OVID RAF / HM20009559
- Conditions
- Atrial Fibrillation and Flutter
- Keywords
- Diltiazem, Atrial Fibrillation, Atrial Flutter, Emergency Medicine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 21 Mar 2021 (actual)
- Study completion
- 21 Mar 2021 (actual)
- First posted
- 21 Mar 2018 (actual)
- Results
- Posted 1 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Immediate Release Diltiazem | Active comparator | Drug: Diltiazem Oral ProductDiltiazem immediate release 60mg orally once (Diltiazem oral product) |
| Continuous Infusion IV Diltiazem | Active comparator | Drug: Diltiazem Injectable ProductDiltiazem 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- >/= 18 years old
- Atrial fibrillation or flutter on electrocardiogram
- Heart rate >110 beats/min
- Systolic blood pressure >/= 90 mmHg
Key exclusion criteria (9 listed)
- Limited English proficiency (LEP)
- Pregnant
- Prisoners
- Wolff Parkinson White syndrome
- Administration of electrical or chemical cardioversion before screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diltiazem Oral ProductDiltiazem Immediate Release 60 MG PO Q6H (30 MG PO Q6H if patient is <60 kg) | Drug | Oral Immediate Release Diltiazem |
| Diltiazem Injectable ProductDiltiazem Continuous Infusion Titrated | Drug | Continuous Infusion IV Diltiazem |
Primary outcome
Heart Rate Control
Time frame: 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
1 secondary outcome
Adverse Event Rate
Time frame: 4 hrs
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tammy T Nguyen, PharmD, BCPS principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diltiazem Oral Product and Diltiazem Injectable Product in people with Atrial Fibrillation and Flutter, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart Rate Control (time frame: 2 hrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.