- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04141553
Bolus vs IVP (Intravenous Push) Diltiazem for Atrial Fibrillation or Flutter
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- Pulmonary edema
- Unstable angina
- Allergy to diltiazem
- Pregnancy
- Breastfeeding
- History of pre-excitation syndrome
- Decompensated heart failure
- Incarcerated persons
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Diltiazem IV push
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.
|
Randomization to one of to active comparator groups
Other Names:
|
Active Comparator: Diltiazem IV Slow Infusion
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.
|
Randomization to one of to active comparator groups
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
within 30 minutes of drug administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Use of additional medications to achieve rate control
Time Frame: within 30 minutes of diltiazem administration
|
Percentage of patients who require medications other than diltiazem to achieve rate control.
|
within 30 minutes of diltiazem administration
|
Frequency of cardioversion
Time Frame: within 30 minutes of diltiazem administration
|
Incidence of electrical cardioversion to achieve rate control
|
within 30 minutes of diltiazem administration
|
Frequency of hospital admission
Time Frame: within 24 hours of study related treatment in the Emergency Department.
|
Percentage of enrolled patients who require hospital admission to achieve and maintain rate control
|
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
|
Characterization and frequency of adverse events
|
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
|
Evaluate occurrence of allergic reactions
|
at the time of diltiazem administration and and immediately following the medication
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Arrhythmias, Cardiac
- Atrial Fibrillation
- Atrial Flutter
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Diltiazem
Other Study ID Numbers
- RATE2019
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atrial Fibrillation
-
Ablacon, Inc.CompletedArrhythmias, Cardiac | Atrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Longstanding Persistent Atrial FibrillationGermany
-
Ablacon, Inc.RecruitingAtrial Fibrillation | Arrhythmias, Cardiac | Arrhythmia | Atrial Flutter | Atrial Fibrillation, Persistent | Atrial Tachycardia | Atrial Arrhythmia | Atrial Fibrillation Paroxysmal | Atrial Fibrillation, Paroxysmal or PersistentUnited States, Belgium, Netherlands, Czechia
-
Barts & The London NHS TrustAtriCure, Inc.Not yet recruitingAtrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Atrial Arrhythmia | Atrium; FibrillationUnited Kingdom
-
AtriCure, Inc.Active, not recruitingPersistent Atrial Fibrillation | Atrial Fibrillation (AF) | Longstanding Persistent Atrial FibrillationUnited States
-
Maastricht University Medical CenterRWTH Aachen UniversityUnknownAtrial Fibrillation (Paroxysmal) | Atrial Fibrillation Recurrent | Atrial Fibrillation Common Gene VariantsNetherlands
-
Vivek ReddyEnrolling by invitationAtrial Fibrillation and Flutter | Atrial Flutter Typical | Atrial Fibrillation, Paroxysmal or PersistentUnited States
-
Adagio MedicalRecruitingAtrial Fibrillation | Atrial Flutter | Paroxysmal Atrial Fibrillation | Persistent Atrial FibrillationNetherlands, Germany, Belgium
-
Fundació Institut de Recerca de l'Hospital de la...RecruitingAtrial Arrhythmia | Atrial Fibrillation and Flutter | Atrial Fibrillation RecurrentSpain
-
St. George's Hospital, LondonRecruitingAtrial Fibrillation | Atrial Fibrillation, Persistent | Persistent Atrial Fibrillation | Atrial ArrhythmiaUnited Kingdom
-
R-PharmFSBI "National Medical Research Center of Cardiology named after academician...CompletedAtrial Flutter | Paroxysmal Atrial Fibrillation | Persistent Atrial FibrillationRussian Federation
Clinical Trials on Diltiazem Injection
-
Ankara UniversityCompleted
-
King Saud UniversityUnknown
-
Eisai Inc.Completed
-
Virginia Commonwealth UniversityCompletedAtrial Fibrillation and FlutterUnited States
-
Ventrus Biosciences, IncUnknownAdult Subjects With Anal Fissures.United States
-
S.L.A. Pharma AGCompletedChronic Anal FissureUnited Kingdom, Spain, Bulgaria, Germany, Lithuania, Romania
-
University Hospital, Strasbourg, FranceUnknownIschaemia-reperfusion InjuryFrance
-
Xuanwu Hospital, BeijingUnknownAcute Ischemic StrokeChina
-
Istanbul Medipol University HospitalCompletedAnal Fissure ChronicTurkey
-
Assiut UniversityUnknownHypotension on Induction