Atrial FibrillationPhase 4NCT04141553
Bolus vs IVP (Intravenous Push) Diltiazem for Atrial Fibrillation or Flutter
A Phase 4 study testing Diltiazem Injection in people with Atrial Fibrillation and Atrial Flutter, run by Mercy Health Muskegon.
Trial summary
The administration of intravenous non-dihydropyridine calcium channel blockers such as diltiazem for patients presenting in atrial fibrillation with rapid ventricular response, without evidence of pre-excitation, are recommended first-line therapies by the American Heart Association.1 Hypotension warrants careful… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Atrial Flutter, Rapid Ventricular Response
- What is being tested?
- Diltiazem Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2019to 1 Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Be 18 years and older,
- Present with atrial fibrillation or atrial flutter with a rapid ventricular response
- Have a 12-lead ECG (electrocardiogram) showing atrial fibrillation or atrial flutter with a rapid ventricular rate greater than 120 beats per minute.
- Able to provide consent for self, or have a legally authorized representative available to provide consent by proxy.
- Have a cardiac history not inclusive of the diagnoses listed under exclusion criteria.
Who cannot join
- Altered mental status as a direct result of hemodynamic instability
- Heart rate >220 beats per minute
- 2nd or 3rd degree atrioventricular block
- QRS (time for ventricular repolarization) >110 milliseconds
- Temperature >38 Celsius
- Acute STEMI (ST-Elevation Myocardial Infarction)
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- Pulmonary edema
- Unstable angina
- Allergy to diltiazem
- Pregnancy
- Breastfeeding
- History of pre-excitation syndrome
- Decompensated heart failure
- Incarcerated persons
About this study
Official title: Gradual Diltiazem Infusion as an Approach to Initial Rate Control in Atrial Fibrillation or Atrial Flutter With Rapid Ventricular Response in the Emergency Setting
The administration of intravenous non-dihydropyridine calcium channel blockers such as diltiazem for patients presenting in atrial fibrillation with rapid ventricular response, without evidence of pre-excitation, are recommended first-line therapies by the American Heart Association.1 Hypotension warrants careful consideration in the treatment of atrial fibrillation with a rapid ventricular response. Hemodynamic stability is a continuum, however, and rate control is often vital, particularly in patients who are refractory to electrical cardioversion [or who have underlying conditions such that tachycardia is not well tolerated]. Diltiazem has been utilized in dosing such as 2.5 mg/min in those with decreased blood pressure and atrial fibrillation with elevated ventricular rate.2 Lim et al. in 2002 demonstrated the effectiveness of a slow infusion of diltiazem 2.5 mg/min to a maximum of 50 mg to control rate in supraventricular tachycardia.
The study of the slow infusion of diltiazem has been limited to supraventricular tachycardia. No literature exists evaluating the efficacy of such a gradual infusion in atrial fibrillation or atrial flutter, rhythms affecting 2.7 million to 6.1 million Americans.1,3 It can be reasoned that a gradual infusion of diltiazem will minimize side effects, predominantly hypotension, and perhaps even demonstrate efficacy in alleviating hypotension due to decreased stroke volume from excessive tachycardia. The proposed benefits of an infusion, as compared to a bolus, would allow for the termination of an infusion as soon as rate control is achieved thus limiting the potential for hypotension. With current evidence-based literature validating the superiority of non-dihydropyridine calcium channel blockers and questions surrounding present recommendations of weight based intravenous dosing, the authors suggest an inquiry into the utility of a gradual infusion of diltiazem for initial rate control in patients presenting with atrial fibrillation or flutter with or without hypotension related to excessive tachycardia.
This is a prospective, randomized, double blind investigation to compare the effectiveness of standard IV (intravenous) push diltiazem at 0.25 mg/kg (to a maximum of 25 mg) over 2 minutes, with a potential repeat dose of 0.35 mg/kg if the initial dose is not effective versus a slow infusion of 50 mg of IV diltiazem diluted in 50 mL of 0.9% normal saline (NS) administered over 20 minutes. The investigators anticipate the data to be collected over the course of 2-3 years. These methods of diltiazem administration are already accepted practices at our institution and are consistent with current approved product labeling and professional judgment based upon clinical experience, and therefore the investigators do not foresee any additional risk to patients enrolled in our proposed study. In either treatment group, should hypotension or other clinical evidence of poor systemic perfusion, no additional IV diltiazem, or additional administration of a diltiazem infusion will be administered. The primary outcome measured will be the efficacy of treatment as defined by the obtainment of a heart rate of <110 beats/minute within 30 minutes of drug administration. Secondary outcomes evaluated will include the need for additional medications to achieve rate control including the need for repeat diltiazem bolus at 0.35 mg/kg, electrical cardioversion, admission, allergic reactions, and side effects including, but not limited to, systolic blood pressure less than 90 mmHg or bradycardia with heart rate less than 60 bpm.
- Being tested
- Diltiazem Injection
- 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 InjectionDrug
Also called diltiazem immediate release oral tablet, 0.9% saline
Randomization to one of to active comparator groups
| Study group | Role | What they receive |
|---|---|---|
| Diltiazem IV push | Active comparator | In the standard IV push group, diltiazem will be administered at a dose of 0.25 mg/kg, to a max dose of 25 mg, over 2 minutes. At time 0, these participants will also receive 30 mg of immediate release oral diltiazem. After 15 minutes, if adequate rate control of <110 BPM has not been achieved, an additional dose 0.35 mg/kg to a max dose of 35 mg will be administered. In order to maintain the blind, the control group will also receive 50 mL of 0.9% NS IV over 20 minutes. Receives: Drug: Diltiazem Injection |
| Diltiazem IV Slow Infusion | Active comparator | In the slow infusion group, 50 mg of diltiazem will be diluted in 50 mL of 0.9% NS and infused over 20 minutes. Similar the other group, these participants will also receive 30 mg of immediate release oral diltiazem. In order to maintain the blind, this slow infusion group will receive the equivalent volume of IV 0.9% NS over 2 minutes as a placebo. Receives: Drug: Diltiazem Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resolution of arrhythmia
Efficacy of treatment as defined by the achievement of a heart rate of <110 beats/minute
Measured: within 30 minutes of drug administration
Secondary outcomes (5)
Use of additional medications to achieve rate control
Percentage of patients who require medications other than diltiazem to achieve rate control.
Measured: within 30 minutes of diltiazem administration
Frequency of cardioversion
Incidence of electrical cardioversion to achieve rate control
Measured: within 30 minutes of diltiazem administration
Frequency of hospital admission
Percentage of enrolled patients who require hospital admission to achieve and maintain rate control
Measured: within 24 hours of study related treatment in the Emergency Department.
Identification of adverse events.
Characterization and frequency of adverse events
Measured: at the time of diltiazem administration and and immediately following the medication
Occurrence of allergic reactions
Evaluate occurrence of allergic reactions
Measured: at the time of diltiazem administration and and immediately following the medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study start1 Dec 2019 (estimated)
- Primary completion1 Dec 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- 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
- Model description
- A parallel randomized blinded model. Eligible and consented participants will be randomized to diltiazem IV push or diltiazem slow bolus. Each will receive an opposite sham infusion of saline provided as IVP push or slow bolus t0 maintain the blind. All participants will receive 30 mg oral dose of diltiazem. Standard of care measures will be provided concurrently as per routine care of patients with atrial fibrillation or atrial flutter with rapid ventricular response Participants will be randomized in 15 blocks of 20 to ensure there are equal numbers of participants in each group for interim analyses. The randomization scheme will allow for 300 participants to account for issues, including dropouts.
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mercy Health Muskegon
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Betcher, MD, Mercy Health Muskegon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04141553
- Sponsor's protocol ID
- RATE2019
- Status last verified
- Oct 2019
- First submitted
- 15 Oct 2019
- Last updated
- 28 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data will not be shared
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gradual Diltiazem Infusion as an Approach to Initial Rate Control in Atrial Fibrillation or Atrial Flutter With Rapid Ventricular Response in the Emergency Setting
- ClinicalTrials.gov ID
- NCT04141553
- Acronym / sponsor ID
- RATE2019
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Mercy Health MuskegonUniversity, hospital or other
- Study start
- 1 Dec 2019 (estimated)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 28 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The administration of intravenous non-dihydropyridine calcium channel blockers such as diltiazem for patients presenting in atrial fibrillation with rapid ventricular response, without evidence of pre-excitation, are recommended first-line therapies by the American Heart Association.1 Hypotension warrants careful consideration in the treatment of atrial fibrillation with a rapid ventricular response. Hemodynamic stability is a continuum, however, and rate control is often vital, particularly in patients who are refractory to electrical cardioversion [or who have underlying conditions such that tachycardia is not well tolerated]. Diltiazem has been utilized in dosing such as 2.5 mg/min in those with decreased blood pressure and atrial fibrillation with elevated ventricular rate.2 Lim et al. in 2002 demonstrated the effectiveness of a slow infusion of diltiazem 2.5 mg/min to a maximum of 50 mg to control rate in supraventricular tachycardia.
The study of the slow infusion of diltiazem has been limited to supraventricular tachycardia. No literature exists evaluating the efficacy of such a gradual infusion in atrial fibrillation or atrial flutter, rhythms affecting 2.7 million to 6.1 million Americans.1,3 It can be reasoned that a gradual infusion of diltiazem will minimize side effects, predominantly hypotension, and perhaps even demonstrate efficacy in alleviating hypotension due to decreased stroke volume from excessive tachycardia. The proposed benefits of an infusion, as compared to a bolus, would allow for the termination of an infusion as soon as rate control is achieved thus limiting the potential for hypotension. With current evidence-based literature validating the superiority of non-dihydropyridine calcium channel blockers and questions surrounding present recommendations of weight based intravenous dosing, the authors suggest an inquiry into the utility of a gradual infusion of diltiazem for initial rate control in patients presenting with atrial fibrillation or flutter with or without hypotension related to excessive tachycardia.
This is a prospective, randomized, double blind investigation to compare the effectiveness of standard IV (intravenous) push diltiazem at 0.25 mg/kg (to a maximum of 25 mg) over 2 minutes, with a potential repeat dose of 0.35 mg/kg if the initial dose is not effective versus a slow infusion of 50 mg of IV diltiazem diluted in 50 mL of 0.9% normal saline (NS) administered over 20 minutes. The investigators anticipate the data to be collected over the course of 2-3 years. These methods of diltiazem administration are already accepted practices at our institution and are consistent with current approved product labeling and professional judgment based upon clinical experience, and therefore the investigators do not foresee any additional risk to patients enrolled in our proposed study. In either treatment group, should hypotension or other clinical evidence of poor systemic perfusion, no additional IV diltiazem, or additional administration of a diltiazem infusion will be administered. The primary outcome measured will be the efficacy of treatment as defined by the obtainment of a heart rate of <110 beats/minute within 30 minutes of drug administration. Secondary outcomes evaluated will include the need for additional medications to achieve rate control including the need for repeat diltiazem bolus at 0.35 mg/kg, electrical cardioversion, admission, allergic reactions, and side effects including, but not limited to, systolic blood pressure less than 90 mmHg or bradycardia with heart rate less than 60 bpm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
- Model description
- A parallel randomized blinded model. Eligible and consented participants will be randomized to diltiazem IV push or diltiazem slow bolus. Each will receive an opposite sham infusion of saline provided as IVP push or slow bolus t0 maintain the blind. All participants will receive 30 mg oral dose of diltiazem. Standard of care measures will be provided concurrently as per routine care of patients with atrial fibrillation or atrial flutter with rapid ventricular response Participants will be randomized in 15 blocks of 20 to ensure there are equal numbers of participants in each group for interim analyses. The randomization scheme will allow for 300 participants to account for issues, including dropouts.
| Arm | Type | Receives |
|---|---|---|
| Diltiazem IV push | Active comparator | Drug: Diltiazem InjectionIn the standard IV push group, diltiazem will be administered at a dose of 0.25 mg/kg, to a max dose of 25 mg, over 2 minutes. At time 0, these participants will also receive 30 mg of immediate release oral diltiazem. After 15 minutes, if adequate rate control of <110 BPM has not been achieved, an additional dose 0.35 mg/kg to a max dose of 35 mg will be administered. In order to maintain the blind, the control group will also receive 50 mL of 0.9% NS IV over 20 minutes. |
| Diltiazem IV Slow Infusion | Active comparator | Drug: Diltiazem InjectionIn the slow infusion group, 50 mg of diltiazem will be diluted in 50 mL of 0.9% NS and infused over 20 minutes. Similar the other group, these participants will also receive 30 mg of immediate release oral diltiazem. In order to maintain the blind, this slow infusion group will receive the equivalent volume of IV 0.9% NS over 2 minutes as a placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Be 18 years and older,
- Present with atrial fibrillation or atrial flutter with a rapid ventricular response
- Have a 12-lead ECG (electrocardiogram) showing atrial fibrillation or atrial flutter with a rapid ventricular rate greater than 120 beats per minute.
- Able to provide consent for self, or have a legally authorized representative available to provide consent by proxy.
- Have a cardiac history not inclusive of the diagnoses listed under exclusion criteria.
Key exclusion criteria (14 listed)
- Altered mental status as a direct result of hemodynamic instability
- Heart rate >220 beats per minute
- 2nd or 3rd degree atrioventricular block
- QRS (time for ventricular repolarization) >110 milliseconds
- Temperature >38 Celsius
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 InjectionAlso: diltiazem immediate release oral tablet, 0.9% salineRandomization to one of to active comparator groups | Drug | Diltiazem IV Slow Infusion, Diltiazem IV push |
Primary outcome
Resolution of arrhythmia
Time frame: within 30 minutes of drug administration
Efficacy of treatment as defined by the achievement of a heart rate of <110 beats/minute
5 secondary outcomes
Use of additional medications to achieve rate control
Time frame: within 30 minutes of diltiazem administration
Frequency of cardioversion
Time frame: within 30 minutes of diltiazem administration
Frequency of hospital admission
Time frame: within 24 hours of study related treatment in the Emergency Department.
Identification of adverse events.
Time frame: at the time of diltiazem administration and and immediately following the medication
Occurrence of allergic reactions
Time frame: at the time of diltiazem administration and and immediately following the medication
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2019.
- Individual participant dataSharing planned: No. Data will not be shared
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Diltiazem Injection in people with Atrial Fibrillation and Atrial Flutter, run by Mercy Health Muskegon.
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 5 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 28 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
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?
Resolution of arrhythmia (time frame: within 30 minutes of drug administration). 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 28 Oct 2019.