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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

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Atrial Fibrillation, RSD1235, Vernakalant, conversion

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT00989001

First Posted

October 1, 2009

Last Updated

February 6, 2014

Sponsor

Advanz Pharma

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

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

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

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

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

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