A Phase 3b Study of Vernakalant Injection in Patients With Recent Onset Symptomatic Atrial Fibrillation (AF)(MK-6621-045) (ACT V)

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

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.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Placebo; Drug: Vernakalant

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.

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vernakalant; Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes	Drug: Vernakalant; Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes; Other Names: RSD1235
Placebo Comparator: Placebo; Placebo (saline) administered IV at same volume and rate as per dosing schedule for vernakalant	Drug: Placebo; Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Occurring within the first two hours after start of study treatment
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	Occurring within 90 minutes of first exposure to study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from First Exposure to Study Treatment to Conversion of AF to SR		Occurring within 90 minutes after study treatment
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	Occurring 90 minutes after first exposure to study treatment

Collaborators and Investigators

• Sponsor: Advanz Pharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (Estimate): October 2, 2009

Study Record Updates

• Last Update Posted (Estimate): March 10, 2014
• Last Update Submitted That Met QC Criteria: February 6, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; conversion; RSD1235; Vernakalant
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 6621-045; 6517-CL-0020 (Other Identifier: Merck); MK-6621-045