Atrial Fibrillation
Conditions
Keywords
Atrial Fibrillation
Brief summary
This study will investigate if treatment with vernakalant hydrochloride (MK-6621) results in a greater proportion of patients with treatment-induced conversion of Atrial Fibrillation to sinus rhythm compared to placebo.
Detailed description
Amendment 4 of the protocol revised the planned enrollment to 123 participants and removed China as one of the countries participating in the study.
Interventions
DRUGvernakalant hydrochloride
Patients will receive a 3 mg/kg infusion of vernakalant hydrochloride. If the patient is in atrial fibrillation (AF) or atrial flutter (AFL) 25 minutes after the start of the infusion, then a second infusion of 2 mg/kg vernakalant hydrochloride will be administered.
DRUGPlacebo to vernakalent hydrochloride
Patients will receive an infusion of placebo. If the patient is in atrial fibrillation (AF) or atrial flutter (AFL) 25 minutes after the start of the infusion, then a second infusion of placebo will be administered.
Sponsors
Advanz Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Abstinent or willing to use 2 acceptable methods of birth control * Patient has an atrial arrhythmia with dysrhythmic symptoms * Patient is receiving adequate anticoagulant therapy * Patient has stable blood pressure * Patient weighs between 45 and 136 kg (99 and 300 lbs) * Patient is adequately hydrated
Exclusion criteria
* Patient is pregnant, breast-feeding, or expecting to become pregnant during the study * Patient routinely consumes more than 2 alcoholic drinks per day * Patient has known or suspected prolonged QT, familial long QT syndrome, previous Torsades de Pointes, Brugada syndrome * Patient has known bradycardia, advanced AV block, or sick-sinus syndrome, unless controlled by a pacemaker * Patient has severe aortic stenosis * Patient has atrial flutter * Patient has Class IV congestive heart failure (CHF) * Patient has had a myocardial infarction (MI) or acute coronary syndrome (ACS) * Patient has had cardiac surgery within 30 days * Patient has known atrial thrombus * Patient has reversible causes of Atrial Fibrillation * Patient has failed electrical cardioversion during current episode of Atrial Fibrillation * Patient has uncorrected electrolyte imbalance * Patient has clinical evidence of digoxin toxicity * Patient has received certain antiarrhythmic drugs or intravenous amiodarone within 7 days * Patient is known to be HIV positive * Patient has a history of cancer within the past 5 years, except for certain skin or cervical cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Treatment-induced Conversion of Atrial Fibrillation to Sinus Rhythm | Within 90 minutes after first exposure | The proportion of patients with treatment-induced conversion of atrial fibrillation to sinus rhythm for a minimum duration of 1 minute |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vernakalant IV vernakalant hydrochloride
Up to two 10-min infusions of 3mg/kg +/- 2mg/kg vernakalant IV | 55 |
| Placebo placebo
Up to two 10-min infusions of normal saline | 56 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 4 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Vernakalant IV | Total |
|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 12 | 60.7 years STANDARD_DEVIATION 13.7 | 59.9 years STANDARD_DEVIATION 12.8 |
| Atrial fibrillation (AF) duration Less than or equal to 48 hours | 31 participants | 33 participants | 64 participants |
| Atrial fibrillation (AF) duration More than 48 hours | 25 participants | 22 participants | 47 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 54 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| New York Heart Association (NYHA) Classification Class I (cardiac disease but no symptoms) | 1 participants | 1 participants | 2 participants |
| New York Heart Association (NYHA) Classification Class III (Marked limitation in activity) | 0 participants | 2 participants | 2 participants |
| New York Heart Association (NYHA) Classification Class II (mild symptoms during normal activity) | 2 participants | 2 participants | 4 participants |
| New York Heart Association (NYHA) Classification None (no heart failure) | 53 participants | 50 participants | 103 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 55 Participants | 55 Participants | 110 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Korea, Republic of | 48 participants | 42 participants | 90 participants |
| Region of Enrollment Taiwan | 7 participants | 13 participants | 20 participants |
| Sex: Female, Male Female | 26 Participants | 18 Participants | 44 Participants |
| Sex: Female, Male Male | 30 Participants | 37 Participants | 67 Participants |
| Structural Heart Disease Congestive Heart Failure | 3 participants | 5 participants | 8 participants |
| Structural Heart Disease Ischemic Heart Disease | 7 participants | 4 participants | 11 participants |
| Structural Heart Disease Myocardial Infarction | 0 participants | 1 participants | 1 participants |
| Structural Heart Disease None | 43 participants | 44 participants | 87 participants |
| Structural Heart Disease Valvular Heart Disease | 3 participants | 2 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 55 | 23 / 56 |
| serious Total, serious adverse events | 6 / 55 | 6 / 56 |
Outcome results
Primary
Proportion of Patients With Treatment-induced Conversion of Atrial Fibrillation to Sinus Rhythm
The proportion of patients with treatment-induced conversion of atrial fibrillation to sinus rhythm for a minimum duration of 1 minute
Time frame: Within 90 minutes after first exposure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vernakalant IV | Proportion of Patients With Treatment-induced Conversion of Atrial Fibrillation to Sinus Rhythm | 29 participants |
| Placebo | Proportion of Patients With Treatment-induced Conversion of Atrial Fibrillation to Sinus Rhythm | 7 participants |