A Phase 3b Study of Vernakalant Injection in Patients With Recent Onset Symptomatic Atrial Fibrillation (AF)(MK-6621-045) (ACT V)
Primary Purpose
Atrial Fibrillation
Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Vernakalant
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Atrial Fibrillation focused on measuring Atrial Fibrillation, RSD1235, Vernakalant, conversion
Eligibility Criteria
Inclusion Criteria:
- Females must be not pregnant or nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 30 days post study treatment
- Subject must have recent onset (> 3 hours to <= 7 days) symptomatic AF to be best managed by acute conversion to SR
- Subject must have adequate anticoagulant therapy
- Subject must have systolic blood pressure (SBP) above 90 mmHg and less than 160 mmHg and diastolic blood pressure (DBP) less than 95 mmHg at screening and baseline
- Subject must have a body weight between 45 and 136 kg, inclusive (99 and 300 lbs)
Exclusion Criteria:
- Subject has a history of heart failure or documentation of left ventricular dysfunction
- Subject has known or suspected prolonged QT or uncorrected QT interval of > 0.440 sec
- Subject has symptomatic bradycardia or ventricular rate less than 50 bpm at Screening, unless controlled by a pacemaker
- Subject has bradycardia (heart rate less than 50 bpm) or hypotension (SBP less that 90 mmHg) after receiving a loading, bolus dose, or sustained infusion of any rate control medication during Screening
- Subject has a QRS interval > 0.14 sec., unless subject has a pacemaker
- Subject had a myocardial infarction (MI), acute coronary syndrome, cardiac surgery (including percutaneous transluminal coronary angioplasty (PTCA) or stent placement), within 30 days prior to enrollment or subject has evidence of new ischemic changes on Screening 12-lead ECG
- Subject has troponin I or T levels beyond the upper limit of normal for the local lab
- Subject has significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis
- Subject has failed electrical cardioversion for AF at anytime
- Subject has failed pharmacologic conversion with an intravenous Class I or Class III antiarrhythmic drug for this episode of AF
- Subject has any known reversible causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, acute pericarditis or hypoxemia
- Subject has uncorrected electrolyte imbalance
- Subject has clinical evidence of digoxin toxicity
- Subject has a history of clinically significant illness (e.g. neurological, gastrointestinal, renal, hepatic, pulmonary, metabolic, endocrine, hematological, or psychiatric), medical condition or laboratory abnormality within 4 weeks prior to Screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Vernakalant
Placebo
Arm Description
Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes
Placebo (saline) administered IV at same volume and rate as per dosing schedule for vernakalant
Outcomes
Primary Outcome Measures
Number of Participants who Experience Hypotension, Ventricular Arrhythmias and/or Death
Hypotension defined as: systolic blood pressure (SBP) <90 mmHg and treated with pressors; SBP <90 mmHg and treated with albumin, dextran or hydroxyethyl starch; or SBP <90 mmHg and seizures. Ventricular arrhythmias defined as: Sustained ventricular tachycardia with a heart rate of >120 beats per minute. Sustained tachycardia defined as lasting >30 seconds; Torsade de Pointes with a duration of >10 seconds; Ventricular fibrillation of any duration.
Number of Participant with Successful Conversion to Sinus rhythm (SR)
Successful conversion defined as return to sinus rhythm for at least 1 minute documented by Holter electrocardiogram (ECG) or by two consecutive 12-lead ECGs recorded > 1 minute apart within 90 minutes of first exposure to study treatment
Secondary Outcome Measures
Time from First Exposure to Study Treatment to Conversion of AF to SR
Number of Participants who Report No Symptoms
Participant was considered a success (no symptoms) if they did not have any of the following symptoms at 90 minutes: palpitations, dyspnea, dizziness, chest pain or fatigue
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00989001
Brief Title
A Phase 3b Study of Vernakalant Injection in Patients With Recent Onset Symptomatic Atrial Fibrillation (AF)(MK-6621-045)
Acronym
ACT V
Official Title
A Phase 3b Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Vernakalant Hydrochloride Injection in Patients With Recent Onset Symptomatic Atrial Fibrillation
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Terminated
Study Start Date
October 2009 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Advanz Pharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of vernakalant injection in subjects with recent onset (AF > 3 hours to <= 7 days), symptomatic atrial fibrillation and no evidence or history of congestive heart failure.
Detailed Description
Participants received a 10-minute intravenous (IV) infusion of vernakalant (3 mg/kg) or an equivalent amount of normal saline (placebo), followed by a 15-minute observation period. If the participant was still in atrial fibrillation or atrial flutter, a second 10-minute IV infusion of vernakalant (2 mg/kg) or an equivalent amount of placebo was administered unless the participant experienced any dose-stopping criteria after the start of the first infusion. If a participant converted to sinus rhythm during the first or second infusion, that infusion was completed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation
Keywords
Atrial Fibrillation, RSD1235, Vernakalant, conversion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
217 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vernakalant
Arm Type
Experimental
Arm Description
Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (saline) administered IV at same volume and rate as per dosing schedule for vernakalant
Intervention Type
Drug
Intervention Name(s)
Vernakalant
Other Intervention Name(s)
RSD1235
Intervention Description
Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Injection
Primary Outcome Measure Information:
Title
Number of Participants who Experience Hypotension, Ventricular Arrhythmias and/or Death
Description
Hypotension defined as: systolic blood pressure (SBP) <90 mmHg and treated with pressors; SBP <90 mmHg and treated with albumin, dextran or hydroxyethyl starch; or SBP <90 mmHg and seizures. Ventricular arrhythmias defined as: Sustained ventricular tachycardia with a heart rate of >120 beats per minute. Sustained tachycardia defined as lasting >30 seconds; Torsade de Pointes with a duration of >10 seconds; Ventricular fibrillation of any duration.
Time Frame
Occurring within the first two hours after start of study treatment
Title
Number of Participant with Successful Conversion to Sinus rhythm (SR)
Description
Successful conversion defined as return to sinus rhythm for at least 1 minute documented by Holter electrocardiogram (ECG) or by two consecutive 12-lead ECGs recorded > 1 minute apart within 90 minutes of first exposure to study treatment
Time Frame
Occurring within 90 minutes of first exposure to study treatment
Secondary Outcome Measure Information:
Title
Time from First Exposure to Study Treatment to Conversion of AF to SR
Time Frame
Occurring within 90 minutes after study treatment
Title
Number of Participants who Report No Symptoms
Description
Participant was considered a success (no symptoms) if they did not have any of the following symptoms at 90 minutes: palpitations, dyspnea, dizziness, chest pain or fatigue
Time Frame
Occurring 90 minutes after first exposure to study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Females must be not pregnant or nursing and if pre-menopausal, must be using an effective form of birth control from time of screening until 30 days post study treatment
Subject must have recent onset (> 3 hours to <= 7 days) symptomatic AF to be best managed by acute conversion to SR
Subject must have adequate anticoagulant therapy
Subject must have systolic blood pressure (SBP) above 90 mmHg and less than 160 mmHg and diastolic blood pressure (DBP) less than 95 mmHg at screening and baseline
Subject must have a body weight between 45 and 136 kg, inclusive (99 and 300 lbs)
Exclusion Criteria:
Subject has a history of heart failure or documentation of left ventricular dysfunction
Subject has known or suspected prolonged QT or uncorrected QT interval of > 0.440 sec
Subject has symptomatic bradycardia or ventricular rate less than 50 bpm at Screening, unless controlled by a pacemaker
Subject has bradycardia (heart rate less than 50 bpm) or hypotension (SBP less that 90 mmHg) after receiving a loading, bolus dose, or sustained infusion of any rate control medication during Screening
Subject has a QRS interval > 0.14 sec., unless subject has a pacemaker
Subject had a myocardial infarction (MI), acute coronary syndrome, cardiac surgery (including percutaneous transluminal coronary angioplasty (PTCA) or stent placement), within 30 days prior to enrollment or subject has evidence of new ischemic changes on Screening 12-lead ECG
Subject has troponin I or T levels beyond the upper limit of normal for the local lab
Subject has significant valvular stenosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy or constrictive pericarditis
Subject has failed electrical cardioversion for AF at anytime
Subject has failed pharmacologic conversion with an intravenous Class I or Class III antiarrhythmic drug for this episode of AF
Subject has any known reversible causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, acute pericarditis or hypoxemia
Subject has uncorrected electrolyte imbalance
Subject has clinical evidence of digoxin toxicity
Subject has a history of clinically significant illness (e.g. neurological, gastrointestinal, renal, hepatic, pulmonary, metabolic, endocrine, hematological, or psychiatric), medical condition or laboratory abnormality within 4 weeks prior to Screening
12. IPD Sharing Statement
Citations:
PubMed Identifier
27233239
Citation
Beatch GN, Mangal B. Safety and efficacy of vernakalant for the conversion of atrial fibrillation to sinus rhythm; a phase 3b randomized controlled trial. BMC Cardiovasc Disord. 2016 May 28;16:113. doi: 10.1186/s12872-016-0289-0.
Results Reference
derived
Learn more about this trial
A Phase 3b Study of Vernakalant Injection in Patients With Recent Onset Symptomatic Atrial Fibrillation (AF)(MK-6621-045)
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