CTAF-2: Efficacy of Perindopril to Prevent Recurrence of Atrial Fibrillation in Patients With Essential Hypertension

Sponsor

Montreal Heart Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00461903

Collaborator

Servier (Industry)

316

Enrollment

Location

Arms

Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this 7- to 13-month study is to determine the efficacy of 8 mg/day oral perindopril to prevent the recurrence of atrial fibrillation (AF) in patients with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension Atrial Fibrillation	Drug: Perindopril	Phase 3

Detailed Description

Hypertension affects approximately 50 million individuals in the United States and approximately 1 billion individuals worldwide. As the population ages, the prevalence of hypertension is expected to increase even further unless broad and effective preventive measures are implemented. Recent data from the Framingham Heart Study suggest that individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension. The relationship between blood pressure (BP) and risk of cardiovascular disease (CVD) events is continuous, consistent, and independent of other risk factors. The higher the BP, the greater is the chance of myocardial infarction, heart failure (HF), stroke, and kidney disease.

Atrial fibrillation (AF) is also a major health problem and has been described as one of two emerging cardiovascular epidemics at the turn of the century. It is the most frequent cardiac arrhythmia, affecting 5% of individuals aged > 65 years, and it is associated with an increased risk of stroke and a doubling of all-cause mortality. The loss of effective atrial contraction may result in impaired cardiac performance, reduced exercise tolerance and congestive heart failure. In addition, patients with atrial fibrillation often have disabling palpitations.

Perindopril (Coversyl) is an angiotensin-converting enzyme (ACE) inhibitor with demonstrated efficacy in controlling hypertension. There are several lines of evidence suggesting that ACE inhibition may reduce the incidence of new-onset AF as well as AF recurrences.

Study Design

Study Type:

Interventional

Actual Enrollment :

316 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomized, Double-blind Placebo-controlled Study to Determine the Efficacy of 8 mg/Day Oral Perindopril to Prevent the Recurrence of Atrial Fibrillation in Patients With Essential Hypertension

Study Start Date :

Dec 1, 2007

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo (for perindopril) Sugar pill manufactued to mimic perindopril	Drug: Perindopril Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study ( Other Names: Coversyl
Active Comparator: Perindopril Perindopril (coversyl) 4 mg tablets	Drug: Perindopril Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study ( Other Names: Coversyl

Arm

Intervention/Treatment

Placebo Comparator: Placebo (for perindopril)

Sugar pill manufactued to mimic perindopril

Drug: Perindopril

Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study (

Other Names:

Coversyl

Active Comparator: Perindopril

Perindopril (coversyl) 4 mg tablets

Drug: Perindopril

Perindopril 4 mg or matching placebo , 1 tablet administrated once daily for the first 2 weeks. If tolarable, dosage increased to 8mg/day until the end of the study (

Other Names:

Coversyl

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint will be time to first sustained recurrence of AF. [12 months follow-up]
1 month treatment adjustment 3 months of endpoint follow-up - M4 6 months of endpoint follow-up - M7 12 months of endpoint follow-up - M13

Secondary Outcome Measures

Secondary efficacy endpoints will be the proportion of patients without AF throughout the 6 months of follow-up, number of documented relapses of AF, and health care resource utilization (including hospitalisations for AF and cardioversions). [6 months follow-up]
Secondary efficacy endpoints will be the proportion of patients without AF throughout the 6 months of follow-up,number of documented relapses of AF, and health care resources utilization (including hospitalisations for AF and cardioversion)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must be age 18 years or older.
Patients may be either male or female without childbearing potential (or with adequate contraception).
Patients must have a current diagnosis of essential hypertension with systolic blood pressure (SBP) ≤ 160 mmHg and diastolic blood pressure (DBP) ≤ 100 mmHg at the time of inclusion visit AND
Patients must have had at least one episode of symptomatic paroxysmal or persistent atrial fibrillation within the preceding six months:
With an indication for cardioversion in the case of persistent AF
With electrocardiogram (ECG) documentation of AF
With duration of an AF episode of at least 10 minutes

Exclusion Criteria:

Unlikely to co-operate in the study
Pregnancy, breastfeeding, or possibility of becoming pregnant during the study (patients must have adequate contraception as determined by the investigator).
Alcoholism or drug abuse
Participation in another study at the same time or within 30 days of randomisation.
Left ventricular systolic dysfunction with an ejection fraction of 45% or less
Myocardial infarction within the past month prior to the selection visit
Cardiac or thoracic surgery within the past 3 months or likely to be performed during the trial
Chronic AF (continuously present for > 6 months)
AF secondary to an acute reversible condition (e.g. post-operative atrial fibrillation, hyperthyroidism)
Currently requiring class I or class III anti-arrhythmic drug therapy (for atrial fibrillation or any other arrhythmia)
Any medical condition that makes the patient an unsuitable candidate in the investigator's opinion
Any medical condition requiring ACE inhibitor or angiotensin-receptor blocker therapy (e.g. diabetes, known proteinuria of more than 300 mg per day)
Renal insufficiency with serum creatinine of 180 μmol/L or greater
Known bilateral renal artery stenosis
Serum potassium of 5.0 mmol/L or greater on recent laboratory exam
Positive pregnancy test (beta human chorionic gonadotropin [HCG] performed in women of childbearing potential)
Known intolerance to ACE inhibitor
Impossibility to discontinue certain treatments at selection visit
Known contraindication(s) to perindopril
Severe known liver disease including cirrhosis, biliary obstruction or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation more than 3 times the upper limit of normal
Use of ACE inhibitor or angiotensin-receptor blocker in the 3 months before the inclusion visit
Severely uncontrolled hypertension with SBP > 160 mmHg or DBP > 100 mmHg at the inclusion visit.