Bolus vs IVP (Intravenous Push) Diltiazem for Atrial Fibrillation or Flutter
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|ClinicalTrials.gov Identifier: NCT04141553|
Recruitment Status : Not yet recruiting
First Posted : October 28, 2019
Last Update Posted : October 28, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation Atrial Flutter Rapid Ventricular Response||Drug: Diltiazem Injection||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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 (Care Provider)|
|Masking Description:||Randomization will be managed by unblinded emergency department pharmacist. This individual will have knowledge of the assigned treatment group for each participant, knowing if diltiazem is provided as IV push or slow infusion. Unblinded pharmacist will also provide sham saline dose, opposite of assigned diltiazem treatment to maintain the blind to care providers.|
|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|
|Estimated Study Start Date :||December 1, 2019|
|Estimated Primary Completion Date :||December 1, 2021|
|Estimated Study Completion Date :||December 1, 2021|
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.
Drug: Diltiazem Injection
Randomization to one of to active comparator groups
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.
Drug: Diltiazem Injection
Randomization to one of to active comparator groups
- 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
- 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.
- Frequency of cardioversion [ Time Frame: within 30 minutes of diltiazem administration ]Incidence of electrical cardioversion to achieve rate control
- 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
- Identification of adverse events. [ Time Frame: at the time of diltiazem administration and and immediately following the medication ]Characterization and frequency of adverse events
- Occurrence of allergic reactions [ Time Frame: at the time of diltiazem administration and and immediately following the medication ]Evaluate occurrence of allergic reactions