Clinical trial NCT00098137: Trial to Investigate the Efficacy of Olmesartan in Paroxysmal Atrial Fibrillation
Official title: Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation Trial (ANTIPAF Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Disease
Arrhythmia
Atrial Fibrillation
Keywords: atrial fibrillation
angiotensin II
angiotensin receptor antagonist
drug
controlled clinical trial
Lead sponsor: Atrial Fibrillation Network
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo
First posted: 2004-12-06
Enrollment: 422
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypothesis:

Blocking the angiotensin (AT) II type 1 receptor (Olmesartan) reduces the incidence of episodes of atrial fibrillation in patients with paroxysmal atrial fibrillation during 12 months by more than 25% compared to standard medication without angiotensin II type 1 receptor.

A total of 422 subjects will be included in the two study groups. The treatment arm will receive 40mg Olmesartan per day, the remaining patients will receive placebo. Follow-up is 12 months. Daily Tele-ECG recordings will determine the cardiac rhythm and asymptomatic episodes of atrial fibrillation (AF) every day. Concomitant therapy with AV-nodal blocking drugs are allowed during the study. In case of severe AF-induced symptoms, an antiarrhythmic "recovery medication" (amiodarone) is allowed during follow-up.

Detailed description: Double-blind, central randomization, two treatment groups, stratified by beta-blocker use. 211 patients in each treatment arm.

Eligibility criteria: Inclusion Criteria:

* Documented paroxysmal atrial fibrillation: ECG documentation of atrial fibrillation at least in one ECG recorded during the last 2 months prior to randomization plus additional ECG recording of sinus rhythm at least 12 hours after the above mentioned ECG documentation.
* Age ≥ 18
* Patient informed orally and in writing
* Written informed consent of the patient

Exclusion Criteria:

* Strong clinical evidence for therapy with AT II/ACE inhibitors
* AT II/ACE inhibitor therapy within the last month
* Therapy with antiarrhythmic agents of class I or class III within the last month, therapy with amiodarone within the last 3 months
* Direct current (DC) cardioversion within the last 3 months
* Symptomatic bradycardia
* Implanted pacemaker or implanted cardioverter/defibrillator with any antitachycardiac algorithm in use
* Cardiac surgery or cardiac catheter ablation within the last 3 months
* Typical angina pectoris symptoms at rest or during exercise
* Known coronary artery disease with indication for intervention
* Valvular disease \> II degree
* Left ventricular ejection fraction \< 40%
* Diastolic blood pressure \> 110mm Hg at rest
* Symptomatic arterial hypotension
* Known renal artery stenosis
* Serum creatinine \> 1.8 mval/l
* Relevant hepatic or pulmonary disorders
* Hyperthyroidism manifested clinically and in laboratory
* Known drug intolerance for AT II inhibitors
* Females who are pregnant or breast feeding
* Females of childbearing potential who are not using a scientifically accepted method of contraception
* Participation in a clinical trial within the last 30 days
* Drug addiction or chronic alcohol abuse
* Legal incapacity, or other circumstances which would prevent the patient from understanding the aim, nature or extent of the clinical study
* Evidence of an uncooperative attitude

Primary outcomes:
measure: Percentage of days with documented episodes of paroxysmal atrial fibrillation (number of days with paroxysmal atrial fibrillation/number of days with at least one readable Tele-ECG recording)
timeFrame: 12 months follow-up
Secondary outcomes:
measure: Time to first occurrence of a documented relapse of atrial fibrillation
timeFrame: 12 months follow up
measure: Time to first occurrence of a symptomatic documented episode of AF
timeFrame: 12 months follow up
measure: Time to persistent atrial fibrillation
timeFrame: 12 months follow up
measure: Time to prescription of the recovery-medication
timeFrame: 12 months follow up
measure: Number of hospitalizations for cardiovascular reasons (-> Endpoint review)
timeFrame: 12 months follow up
measure: Number of intermediate medical visits for cardiovascular reasons (-> Endpoint review) without hospitalization
timeFrame: 12 months follow up
measure: Number of cerebrovascular events
timeFrame: 12 months follow up
measure: Quality of life
timeFrame: 12 months follow up
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital Hamburg
name: Thomas Meinertz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Magdeburg
name: Andreas Goette, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: von Eisenhart Rothe AF, Goette A, Kirchhof P, Breithardt G, Limbourg T, Calvert M, Baumert J, Ladwig KH. Depression in paroxysmal and persistent atrial fibrillation patients: a cross-sectional comparison of patients enroled in two large clinical trials. Europace. 2014 Jun;16(6):812-9. doi: 10.1093/europace/eut361. Epub 2013 Dec 18.
citation: von Eisenhart Rothe A, Bielitzer M, Meinertz T, Limbourg T, Ladwig KH, Goette A. Predictors of discordance between physicians' and patients' appraisals of health-related quality of life in atrial fibrillation patients: findings from the Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation Trial. Am Heart J. 2013 Sep;166(3):589-96. doi: 10.1016/j.ahj.2013.05.020. Epub 2013 Jul 10.
citation: Goette A, Schon N, Kirchhof P, Breithardt G, Fetsch T, Hausler KG, Klein HU, Steinbeck G, Wegscheider K, Meinertz T. Angiotensin II-antagonist in paroxysmal atrial fibrillation (ANTIPAF) trial. Circ Arrhythm Electrophysiol. 2012 Feb;5(1):43-51. doi: 10.1161/CIRCEP.111.965178. Epub 2011 Dec 7.