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

Atrial Fibrillation Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00989001
• Other study ID #: 6621-045
• Secondary ID: 6517-CL-0020MK-6
• Status: Terminated
• Phase: Phase 3
• First received: October 1, 2009
• Last updated: February 6, 2014
• Start date: October 2009
• Est. completion date: November 2010

Study information

• Verified date: February 2014
• Source: Cardiome Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaMexico: Federal Commission for Sanitary Risks ProtectionPeru: Instituto Nacional de SaludChile: Instituto de Salud Pública de ChileSouth Africa: Medicines Control CouncilIsrael: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: The Central Register of Clinical Trials
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 217
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Vernakalant
Maximum volume of 100 mL as per the dosing schedule, administered intravenously (IV) over 10 minutes
• Placebo
Injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cardiome Pharma

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	No
Secondary	Time from First Exposure to Study Treatment to Conversion of AF to SR		Occurring within 90 minutes after study treatment	No
Secondary	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	No