Clinical trial NCT00262119: MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
Official title: MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Heart Failure, Congestive
Keywords: Physiological pacing
Antitachycardia pacing therapies
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2005-12-06
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to test the impact of the managed ventricular pacing (MVP) mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed of any death, permanent atrial fibrillation, and cardiovascular hospitalizations.

Detailed description: Kristensen et al. reported that AAIR pacing reduces atrial fibrillation (AF) development compared to DDDR pacing in sinus node disfunction patients.

Several authors have shown that, in patients with intact AV conduction, unnecessary chronic RV pacing can cause detrimental effects such as AF, left ventricular (LV) dysfunction and congestive heart failure. These findings arose the hypothesis that the non-physiologic nature of ventricular pacing may result in electrophysiological and LV remodeling changes that have potentially deleterious long-term effects.

The MVP mode, present in the Medtronic pacemaker EnRhythm, provides atrial based pacing with ventricular backup. It operates in true AAI(R) mode, it provides ventricular backup in case of a single conduction loss and converts to DDD(R) mode in case of persistent loss of AV conduction.

Aim of this study is to test the impact of the MVP pacing mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed by any death, permanent AF, cardiovascular hospitalizations.

Eligibility criteria: Inclusion Criteria:

* Class I/Class II indications for dual chamber pacing
* Previous implant of an EnRhythm dual chamber implantable pulse generator (IPG) since maximum 2 weeks
* History of atrial arrhythmias (at least one electrocardiogram \[ECG\] or Holter documented episodes in the last 12 months)

Exclusion Criteria:

* Less than 18 years of age
* Pregnancy
* Unwilling or unable to give informed consent or to commit to follow-up schedule
* Medical conditions that preclude protocol required testing or limit study participation
* Enrolled or intend to participate in another clinical trial during the course of this study
* A life expectancy of less than 2 years
* Patient is a candidate for an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device implant
* Anticipated major cardiac surgery within the course of this study
* Permanent III degree AV-block or history of AV node ablation
* History of permanent AF (as defined below)
* AF ablation (left pulmonary veins) or other cardiac surgery \< 3 months
* Prior implant of defibrillator device or pacemaker (apart from EnRhythm IPG implanted within two weeks)
* Uncontrolled hyperthyroidism

Primary outcomes:
measure: Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years
timeFrame: 2 years
Secondary outcomes:
measure: Death for All Causes at 2 Years
timeFrame: 2 years
measure: Incidence of Permanent Atrial Fibrillation at 2 Years
timeFrame: 2 years
measure: Incidence of Cardiovascular Hospitalizations at 2 Years
timeFrame: 2 years
measure: Burden of Composite Clinical Endpoint
timeFrame: 2 years
measure: Subjects' Symptoms
timeFrame: 2 years
measure: Heart Failure Medications
timeFrame: 2 years
measure: Cumulative Percentage of Ventricular Pacing
timeFrame: 2 years
measure: Cardiovascular Death
timeFrame: 2 years
measure: Any Hospitalization
timeFrame: 2 years
measure: Atrial Fibrillation Burden
timeFrame: 2 years
measure: Persistent Atrial Fibrillation (AF)
timeFrame: 2 years
measure: Adverse Events
timeFrame: 2 years
measure: Development of Atrioventricular (AV) Block and Pacemaker Dependency
timeFrame: 2 years
measure: Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism
timeFrame: 2 years
measure: Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation
timeFrame: 2 years
measure: Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay
timeFrame: 2 years
measure: Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients
timeFrame: 2 years
measure: Frequency, Type, and Associated Cost of Health Care Utilization and Utility
timeFrame: 2 years
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Medtronic Italia S.p.A.
Study officials:
affiliation: Ospedale Careggi - Firenze
name: Luigi Padeletti, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale Sant'Orsola - Bologna
name: Giuseppe Boriani, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona
name: Luis Mont, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Philipps University Hospital - Marburg
name: Reinhard C Funck, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: J. W. Goethe University Hospital - Frankfurt
name: Carsten W Israel, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Elisabethinen Hospital
name: Helmut Pürerfellner, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Evagelismos Hospital - Athens
name: Antonis S Manolis, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint-Joseph - Marseille
name: André Pisapia, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Kennemer Gasthuis
name: Raymond Tukkie, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91. doi: 10.1056/NEJM200005113421902.
citation: Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA 3rd, Greenspon A, Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002 Jun 13;346(24):1854-62. doi: 10.1056/NEJMoa013040.
citation: Mattioli AV, Vivoli D, Mattioli G. Influence of pacing modalities on the incidence of atrial fibrillation in patients without prior atrial fibrillation. A prospective study. Eur Heart J. 1998 Feb;19(2):282-6. doi: 10.1053/euhj.1997.0616.
citation: Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. 1997 Oct 25;350(9086):1210-6. doi: 10.1016/S0140-6736(97)03425-9.
citation: Kristensen L, Nielsen JC, Mortensen PT, Pedersen OL, Pedersen AK, Andersen HR. Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart. 2004 Jun;90(6):661-6. doi: 10.1136/hrt.2003.016063.
citation: Nielsen JC, Andersen HR, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single-chamber atrial or ventricular pacing. Circulation. 1998 Mar 17;97(10):987-95. doi: 10.1161/01.cir.97.10.987.
citation: Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol. 2003 Aug 20;42(4):614-23. doi: 10.1016/s0735-1097(03)00757-5.
citation: Boriani G, Tukkie R, Manolis AS, Mont L, Purerfellner H, Santini M, Inama G, Serra P, de Sousa J, Botto GL, Mangoni L, Grammatico A, Padeletti L; MINERVA Investigators. Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial. Eur Heart J. 2014 Sep 14;35(35):2352-62. doi: 10.1093/eurheartj/ehu165. Epub 2014 Apr 25.
citation: Funck RC, Boriani G, Manolis AS, Puererfellner H, Mont L, Tukkie R, Pisapia A, Israel CW, Grovale N, Grammatico A, Padeletti L; MINERVA Study Group. The MINERVA study design and rationale: a controlled randomized trial to assess the clinical benefit of minimizing ventricular pacing in pacemaker patients with atrial tachyarrhythmias. Am Heart J. 2008 Sep;156(3):445-51. doi: 10.1016/j.ahj.2008.05.004.