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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group | Active Comparator | PM programming according to actual clinical practice |
|
| MVP Only | Active Comparator | PM programming according to actual clinical practice + MVP algorithm ON |
|
| DDDRP | Active Comparator | PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pacemaker Medtronic EnRhythm | Device | Pacemaker specific programming |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | The outcome measurement is the 2 years incidence, calculated by Kaplan Meier survival analysis, of the composite endpoint composed by death for any cause, cardiovascular hospitalization or permanent AF. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Death for All Causes at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years | 2 years |
| Incidence of Permanent Atrial Fibrillation at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Luigi Padeletti, Prof. | Ospedale Careggi - Firenze | Principal Investigator |
| Giuseppe Boriani, Dr. | Ospedale Sant'Orsola - Bologna | Principal Investigator |
| Luis Mont, Dr. | Hospital Clinic of Barcelona | Principal Investigator |
| Reinhard C Funck, Dr. | Philipps University Hospital - Marburg | Principal Investigator |
| Carsten W Israel, Dr. | J. W. Goethe University Hospital - Frankfurt | Principal Investigator |
| Helmut Pürerfellner, Dr. | Elisabethinen Hospital | Principal Investigator |
| Antonis S Manolis, Prof. | Evagelismos Hospital - Athens | Principal Investigator |
| André Pisapia, Dr | Hôpital Saint-Joseph - Marseille | Principal Investigator |
| Raymond Tukkie, Dr | Kennemer Gasthuis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medtronic Italia S.p.A. | Rome | 00193 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10805823 | Background | 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. | |
| 12063369 |
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A total of 1300 patients were enrolled in the study. Enrollment was followed by a 1-month run-in period. Patients with ventricular pacing ≥ 95% on device check in the run-in period were excluded from the study. At the end of the run-in period, randomization was performed. In all, 1166 patients were randomized and followed up.
The recruitment period was between February 2006 and April 2010. Patients were enrolled in cardiology departments.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Group | PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| FG001 | MVP Only | PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| FG002 | DDDRP | PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Group | PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| BG001 | MVP Only | PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Death for All Causes at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years | The analysis was intention to treat therefore all randomized patients were included in the analysis | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Group | PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Clinical Research Manager | Medtronic | 0039-0632814225 | andrea.grammatico@medtronic.com |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| 2 years |
| Incidence of Cardiovascular Hospitalizations at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years | 2 years |
| Burden of Composite Clinical Endpoint | 2 years |
| Subjects' Symptoms | 2 years |
| Heart Failure Medications | 2 years |
| Cumulative Percentage of Ventricular Pacing | 2 years |
| Cardiovascular Death | 2 years |
| Any Hospitalization | 2 years |
| Atrial Fibrillation Burden | 2 years |
| Persistent Atrial Fibrillation (AF) | 2 years |
| Adverse Events | 2 years |
| Development of Atrioventricular (AV) Block and Pacemaker Dependency | 2 years |
| Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism | 2 years |
| Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation | 2 years |
| Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay | 2 years |
| Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients | 2 years |
| Frequency, Type, and Associated Cost of Health Care Utilization and Utility | 2 years |
| 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. |
| 9519322 | Background | 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. |
| 9652562 | Background | 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. |
| 15145874 | Background | 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. |
| 9529267 | Background | 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. |
| 12932590 | Background | 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. |
| 24771721 | Derived | 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. |
| 18760124 | Derived | 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. |
| BG002 | DDDRP | PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | DDDRP | PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming |
|
|
| Secondary | Incidence of Permanent Atrial Fibrillation at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years | The analysis was intention to treat therefore all randomized patients were analysed | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
|
|
| Secondary | Incidence of Cardiovascular Hospitalizations at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years | Analysis was intention to treat therefore all randomized patients were analysed | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
|
|
| Secondary | Burden of Composite Clinical Endpoint | Not Posted | 2 years | Participants |
| Secondary | Subjects' Symptoms | Not Posted | 2 years | Participants |
| Secondary | Heart Failure Medications | Not Posted | 2 years | Participants |
| Secondary | Cumulative Percentage of Ventricular Pacing | Not Posted | 2 years | Participants |
| Secondary | Cardiovascular Death | Not Posted | 2 years | Participants |
| Secondary | Any Hospitalization | Not Posted | 2 years | Participants |
| Secondary | Atrial Fibrillation Burden | Not Posted | 2 years | Participants |
| Secondary | Persistent Atrial Fibrillation (AF) | Not Posted | 2 years | Participants |
| Secondary | Adverse Events | Not Posted | 2 years | Participants |
| Secondary | Development of Atrioventricular (AV) Block and Pacemaker Dependency | Not Posted | 2 years | Participants |
| Secondary | Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism | Not Posted | 2 years | Participants |
| Secondary | Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation | Not Posted | 2 years | Participants |
| Secondary | Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay | Not Posted | 2 years | Participants |
| Secondary | Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients | Not Posted | 2 years | Participants |
| Secondary | Frequency, Type, and Associated Cost of Health Care Utilization and Utility | Not Posted | 2 years | Participants |
| Primary | Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | The outcome measurement is the 2 years incidence, calculated by Kaplan Meier survival analysis, of the composite endpoint composed by death for any cause, cardiovascular hospitalization or permanent AF. | Analysis was intention to treat therefore all randomized patients were considered in the analyses | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
|
|
| 180 |
| 385 |
| 0 |
| 385 |
| EG001 | MVP Only | PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming | 165 | 398 | 0 | 398 |
| EG002 | DDDRP | PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming | 169 | 383 | 0 | 383 |
| Coagulation problem | Blood and lymphatic system disorders | Systematic Assessment |
|
| Acute Cornary Syndrome/Acute Myocardial Infarction | Cardiac disorders | Systematic Assessment |
|
| Atrial Arrhythmia | Cardiac disorders | Systematic Assessment |
|
| AV conduction disorders | Cardiac disorders | Systematic Assessment |
|
| Cardiac death | Cardiac disorders | Systematic Assessment |
|
| General cardiovascular disorders | Cardiac disorders | Systematic Assessment |
|
| Heart Failure | Cardiac disorders | Systematic Assessment |
|
| Sudden Cardiac Arrest | Cardiac disorders | Systematic Assessment |
|
| Sympthoms of chest pain, angina, palpitation, dyspnea on exertion or cardiopalmo | Cardiac disorders | Systematic Assessment |
|
| Ventricular Tachycardia or Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Glucose metabolism disorders | Endocrine disorders | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | Systematic Assessment |
|
| Eye disease | Eye disorders | Systematic Assessment |
|
| Gastrointestinal disorders | Gastrointestinal disorders | Systematic Assessment |
|
| Death for non cardiac reason | General disorders | Systematic Assessment |
|
| Death for unknown causes | General disorders | Systematic Assessment |
|
| Hemorrage | General disorders | Systematic Assessment |
|
| Hypertension | General disorders | Systematic Assessment |
|
| Other general disorders | General disorders | Systematic Assessment |
|
| Syncope | General disorders | Systematic Assessment |
|
| Gallbladdert disorder | Hepatobiliary disorders | Systematic Assessment |
|
| Hepatic disorder | Hepatobiliary disorders | Systematic Assessment |
|
| Infection and infestations | Infections and infestations | Systematic Assessment |
|
| Consequences of drugs administration | Injury, poisoning and procedural complications | Systematic Assessment |
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| Lead dislodgement | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Pacemaker/Lead related complications | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Ureteral catheter dysfunction or dislodgement | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Enteroscopy, colonoscopy or video capsule endoscopy procedure | Investigations | Systematic Assessment |
|
| Muscoloskeletal disease | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Neoplasia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Prostate disorder | Renal and urinary disorders | Systematic Assessment |
|
| Renal or urinary disease | Renal and urinary disorders | Systematic Assessment |
|
| Acute Pulmonary Edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Cronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Symptoms of dyspnea, shortness of breath, fatigue, cough and or tachypnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Ablation | Surgical and medical procedures | Systematic Assessment |
|
| Coronary Artery Bypass Graft | Surgical and medical procedures | Systematic Assessment |
|
| Other cardiac surgical interventions | Surgical and medical procedures | Systematic Assessment |
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| Other surgical interventions | Surgical and medical procedures | Systematic Assessment |
|
| Pacemaker replacement, explant or repositioning | Surgical and medical procedures | Systematic Assessment |
|
| Stent implantation/Angiography | Surgical and medical procedures | Systematic Assessment |
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| Aneurysm | Vascular disorders | Systematic Assessment |
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| Coronary Artery Disease | Vascular disorders | Systematic Assessment |
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| Other cerebrovascular disorders | Vascular disorders | Systematic Assessment |
|
| Other vascular disorders | Vascular disorders | Systematic Assessment |
|
| Peripheral vascular disease | Vascular disorders | Systematic Assessment |
|
| Stroke | Vascular disorders | Systematic Assessment |
|
| Transient Ischemic Attack | Vascular disorders | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |