Atrial Fibrillation With Rapid Ventricular Response, Hypotension Drug-Induced
Conditions
Keywords
diltiazem, calcium
Brief summary
The purpose of this study is to see how well calcium pre-treatment works for decreasing incidence of drug-induced hypotension after diltiazem administration for treatment of atrial flutter with rapid ventricular rate.
Detailed description
Non-dihydropyridine calcium channel blockers(CCB) are routinely used in the treatment of atrial fibrillation or flutter with rapid ventricular response (AFF with RVR); however, their use can be limited by drug-induced hypotension. This drug induced hypotension limits and complicates CCB use in the treatment of AFF with RVR. Calcium pre-treatment with calcium channel blocker administration has been studied extensively with verapamil administration in preventing drug induced hypotension however, similar studies evaluating calcium pretreatment with diltiazem administration in the prevention of drug-induced hypotension are limited. The purpose of this study is to compare the relative efficacy and safety for calcium pretreatment with diltiazem in the treatment of AFF with RVR in preventing drug-induced hypotension. This prospective, randomized double-blinded study will evaluate patients who present to the emergency department at Advocate Christ Medical Center with a diagnosis of AFF with RVR with ventricular rate greater than or equal to 120 beats per minute from IRB approval to June 1, 2024. Via simple randomization, patients will be administered calcium pretreatment versus control prior to diltiazem administration. Calcium gluconate 1 gm or 100 mL of normal saline will be administered as an intravenous infusion over 5 minutes followed by bolus diltiazem 0.25 mg/kg IV push (with a 20 mg max) with repeat diltiazem bolus dose after 15 minutes if rate control not achieved 0.35mg/kg IV push. Calcium gluconate will not be administered with repeat doses of diltiazem. Weight-based dosing of diltiazem was most utilized, though some providers may elect to modify based on the clinical scenario. The primary outcome will be the mean difference in systolic blood pressure evaluated at 5 and 15 minutes after administration of diltiazem bolus. Secondary outcomes include decrease in heart rate, conversion to sinus rhythm, and adverse effects of medication administered.
Interventions
DRUGCalcium pre-treatment
The intervention is Calcium gluconate 1 gram/100ml 0.9% NaCl or 100ml 0.9% NaCl) over 5 minutes.
OTHERPlacebo
Placebo/ no calcium pre-treatment.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years or older * Able to provide informed consent * Primary diagnosis AFF with RVR greater than or equal to 120 bpm
Exclusion criteria
* Pregnancy defined as a positive urine HCG * Hemodynamically unstable patients (SBP \<90, MAP \<65) * Stated history of systolic heart failure with reduced ejection fraction (\<40%) or evidence of acute heart failure or reduced EF (peripheral edema, JVD, pulmonary edema) on clinical exam or bedside echo * Patients with left ventricular assist device * Sinus node dysfunction or preexcitation with accessory pathway (known diagnosis of SVT, WPW or sick sinus syndrome. Delta waves or other evidence of accessory pathway on EKG) * 2nd or 3rd degree atrioventricular block * Allergy or sensitivity to any study drugs * Previously enrolled in this trial during a different patient encounter * Non-English speaking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference in Systolic Blood Pressure | Baseline to 5 Minutes | Mean difference in systolic blood pressure after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Heart Rate | Baseline to 5 Minutes | Mean difference in heart rate evaluated after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem. |
| Heart Rhythm at 5 Minutes | Baseline to 5 Minutes | Heart rhythm category after 5 minutes of initial diltiazem administration for treatment of AFF with RVR. |
| Heart Rhythm at 15 Minutes | Baseline to 15 Minutes | Heart rhythm category after 15 minutes of initial diltiazem administration for treatment of AFF with RVR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcium Pre-treatment Calcium gluconate 1 gram/100ml 0.9% NaCl or 100ml 0.9% NaCl
Calcium pre-treatment: The intervention is Calcium gluconate 1 gram/100ml 0.9% NaCl or 100ml 0.9% NaCl) over 5 minutes. | 44 |
| Placebo diluent (NS) vials
Placebo: Placebo/ no calcium pre-treatment. | 39 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Nine patients were excluded due to change in hemodynamic status and consent withdrawal. | 2 | 7 |
Baseline characteristics
| Characteristic | Total | Placebo | Calcium Pre-treatment |
|---|---|---|---|
| Age, Continuous | 67.7711 years STANDARD_DEVIATION 11.1107 | 68.6923 years STANDARD_DEVIATION 11.3721 | 66.9545 years STANDARD_DEVIATION 10.9395 |
| Height (cm) | 170.2000 centimeters | 172.7000 centimeters | 167.6000 centimeters |
| On rate Control Medicine (yes/no)? No | 54 Participants | 23 Participants | 31 Participants |
| On rate Control Medicine (yes/no)? Yes | 29 Participants | 16 Participants | 13 Participants |
| On Rhythm Medication for PTA? No | 82 Participants | 38 Participants | 44 Participants |
| On Rhythm Medication for PTA? Yes | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 8 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 60 Participants | 30 Participants | 30 Participants |
| Region of Enrollment United States | 83 participants | 39 participants | 44 participants |
| Sex: Female, Male Female | 43 Participants | 23 Participants | 20 Participants |
| Sex: Female, Male Male | 40 Participants | 16 Participants | 24 Participants |
| Weight (kg) | 87.3000 kilograms | 90.1500 kilograms | 87.1000 kilograms |
| Which Rate Control Agent? Digoxin | 3 Participants | 2 Participants | 1 Participants |
| Which Rate Control Agent? Diltiazem | 20 Participants | 10 Participants | 10 Participants |
| Which Rate Control Agent? Metroprolol | 2 Participants | 2 Participants | 0 Participants |
| Which Rate Control Agent? Not on Rate Controlled Agent | 54 Participants | 23 Participants | 31 Participants |
| Which Rate Control Agent? Other | 4 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 39 |
| other Total, other adverse events | 5 / 44 | 2 / 39 |
| serious Total, serious adverse events | 0 / 44 | 0 / 39 |
Outcome results
Primary
Mean Difference in Systolic Blood Pressure
Mean difference in systolic blood pressure evaluated after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem.
Time frame: Baseline to 10 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Difference in Systolic Blood Pressure | -7.8182 mmHg | Standard Deviation 14.4484 |
| Placebo | Mean Difference in Systolic Blood Pressure | -16.2564 mmHg | Standard Deviation 15.066 |
Primary
Mean Difference in Systolic Blood Pressure
Mean difference in systolic blood pressure after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem
Time frame: Baseline to 15 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Difference in Systolic Blood Pressure | -7.2273 mmHg | Standard Deviation 14.1994 |
| Placebo | Mean Difference in Systolic Blood Pressure | -13.6667 mmHg | Standard Deviation 16.1267 |
Primary
Mean Difference in Systolic Blood Pressure
Mean difference in systolic blood pressure after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem.
Time frame: Baseline to 5 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Difference in Systolic Blood Pressure | -11.7500 mmHg | Standard Deviation 15.7689 |
| Placebo | Mean Difference in Systolic Blood Pressure | -19.5385 mmHg | Standard Deviation 16.1259 |
Secondary
Heart Rhythm at 15 Minutes
Heart rhythm category after 15 minutes of initial diltiazem administration for treatment of AFF with RVR.
Time frame: Baseline to 15 Minutes
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Calcium Pre-treatment | Heart Rhythm at 15 Minutes | AFF | 36 Participants |
| Calcium Pre-treatment | Heart Rhythm at 15 Minutes | AFF RVR | 6 Participants |
| Calcium Pre-treatment | Heart Rhythm at 15 Minutes | NSR | 2 Participants |
| Placebo | Heart Rhythm at 15 Minutes | AFF | 27 Participants |
| Placebo | Heart Rhythm at 15 Minutes | AFF RVR | 10 Participants |
| Placebo | Heart Rhythm at 15 Minutes | NSR | 2 Participants |
Secondary
Heart Rhythm at 5 Minutes
Heart rhythm category after 5 minutes of initial diltiazem administration for treatment of AFF with RVR.
Time frame: Baseline to 5 Minutes
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Calcium Pre-treatment | Heart Rhythm at 5 Minutes | AFF | 36 Participants |
| Calcium Pre-treatment | Heart Rhythm at 5 Minutes | AFF RVR | 7 Participants |
| Calcium Pre-treatment | Heart Rhythm at 5 Minutes | NSR | 1 Participants |
| Placebo | Heart Rhythm at 5 Minutes | AFF | 29 Participants |
| Placebo | Heart Rhythm at 5 Minutes | AFF RVR | 9 Participants |
| Placebo | Heart Rhythm at 5 Minutes | NSR | 1 Participants |
Secondary
Mean Change in Heart Rate
Mean difference in heart rate evaluated after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem.
Time frame: Baseline to 10 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Change in Heart Rate | -43.9545 beats per minute | Standard Deviation 19.6551 |
| Placebo | Mean Change in Heart Rate | -35.0000 beats per minute | Standard Deviation 21.5174 |
Secondary
Mean Change in Heart Rate
Mean difference in heart rate evaluated after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem.
Time frame: Baseline to 15 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Change in Heart Rate | -43.1136 beats per minute | Standard Deviation 19.186 |
| Placebo | Mean Change in Heart Rate | -33.7949 beats per minute | Standard Deviation 22.2405 |
Secondary
Mean Change in Heart Rate
Mean difference in heart rate evaluated after administration of diltiazem bolus. Monitors were set to obtain an automated full set of vitals every 5 minutes after administration of diltiazem.
Time frame: Baseline to 5 Minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcium Pre-treatment | Mean Change in Heart Rate | -37.8864 beats per minute | Standard Deviation 21.5355 |
| Placebo | Mean Change in Heart Rate | -36.2564 beats per minute | Standard Deviation 20.6687 |