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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Cardiome Pharma
ClinicalTrials.gov Identifier:
NCT00989001
First received: October 1, 2009
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Drug: Vernakalant
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cardiome Pharma:

Primary Outcome Measures:
  • Number of Participants who Experience Hypotension, Ventricular Arrhythmias and/or Death [ Time Frame: Occurring within the first two hours after start of study treatment ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Occurring within 90 minutes of first exposure to study treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Occurring within 90 minutes after study treatment ] [ Designated as safety issue: No ]
  • Number of Participants who Report No Symptoms [ Time Frame: Occurring 90 minutes after first exposure to study treatment ] [ Designated as safety issue: No ]
    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


Enrollment: 217
Study Start Date: October 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: RSD1235
Placebo Comparator: Placebo
Placebo (saline) administered IV at same volume and rate as per dosing schedule for vernakalant
Drug: Placebo
Injection

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Cardiome Pharma
ClinicalTrials.gov Identifier: NCT00989001     History of Changes
Other Study ID Numbers: 6621-045, 6517-CL-0020, MK-6621-045
Study First Received: October 1, 2009
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Instituto Nacional de Salud
Chile: Instituto de Salud Pública de Chile
South Africa: Medicines Control Council
Israel: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Central Register of Clinical Trials

Keywords provided by Cardiome Pharma:
Atrial Fibrillation
RSD1235
Vernakalant
conversion

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014