ACCESS-Europe A Two-Phase Observational Study of the MitraClip® System in Europe

Study Overview
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Brief Summary
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The MitraClip System enables the European physicians an alternative therapeutic option for patients with mitral regurgitation (MR). Therapeutic alternatives are open-heart cardiac surgery, and palliative medical therapy with or without device therapy. The study will observe the outcomes of patients treated with the MitraClip System throughout 12-months as compared to the outcomes of patients treated by alternative therapies.

Detailed Description
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PHASE I: The primary objective of ACCESS-EU Phase I is to gain information in the European Union Countries regarding the use of the MitraClip System with respect to health economics and clinical care. PHASE II: (HAS BEEN CLOSED BY SPONSOR) The primary objective of ACCESS-EU Phase II is to gather additional clinical data, specifically Echocardiography Core Laboratory measurements of MR severity and left ventricular volumes and diameters, and other echocardiographic measures, on patients undergoing the MitraClip procedure in the European Union Countries, Clinical data collected from both study phases, is expected to contribute to decision making with regards to MitraClip therapy selection in patients with MR: (a) by establishing the value of the MitraClip therapy in the continuum of care; and (b) by providing practical information that will allow physicians to make therapeutic decisions, assist hospitals to make purchasing decisions, and assist insurers in making coverage decisions. Study Design: ACCESS-Europe is a two-phase prospective, observational, multicenter post-approval study of the MitraClip System for the treatment of mitral regurgitation (MR) in the European Union Countries. Patients will be evaluated per standard practice at baseline, discharge, 6-Months and 12-Months. Phase I of the study consists of patients who receive the MitraClip system for the treatment of MR and two concurrent comparator groups of (a) medically managed heart failure patients with MR and (b) patients who have undergone mitral valve surgery for MR. The two comparator groups will be followed and evaluated primarily from a health economic perspective. ACCESS EU Study Phase II will consist of only patients who receive the MitraClip System, with the objective to collect additional clinical data, specifically Echocardiography Core Laboratory evaluation of MR severity and other echocardiographic measures. Enrollment of patients in each study phase is as follows: ACCESS-EU PHASE I: A minimum of 300 MitraClip Therapy group patients, A minimum of 100 patients in the Mitral Valve Surgery comparator group As many patients as possible in the Medical Therapy comparator group First Patient Enrollment Projection: Q1, 2009 Last Patient Enrollment Projection: Enrollment in the Mitral Valve Surgery and Medically Therapy groups ceased on December 31, 2010. Enrollment in the MitraClip group will cease when Phase II of the study is initiated at each site. ACCESS-EU PHASE II: A minimum of 300 MitraClip therapy subjects will be enrolled in Phase II. First Patient Enrollment Projection: Q2, 2011 Last Patient Enrollment Projection: Enrollment will cease when the Sponsor has determined that an adequate number of patients have been enrolled.

Official Title
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ACCESS-Europe A Two-Phase Observational Study of the MitraClip® System in Europe

Conditions
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Mitral Valve (MV) Regurgitation

Intervention / Treatment
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* Device: MitraClip
* Drug: Medical Management
* Procedure: Mitral Valve Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Per the current approved labeling for the Conformity European (CE) Marked MitraClip System. Exclusion Criteria: Per the current approved labeling for the CE Marked MitraClip System.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MitraClip Therapy<br>Patients treated with the MitraClip System. | Device: MitraClip<br>* The MitraClip System includes a MitraClip device, a Steerable Guide Catheter, and a MitraClip Delivery System that enables placement of the MitraClip device on the mitral valve leaflets<br>|
| Medical Management<br>Patients with MR managed non-surgically based on standard hospital clinical practice. | Drug: Medical Management<br>* The Non-Surgical Medically Managed Heart Failure (HF) Group consists of patients with mitral regurgitation (MR) in whom the MR is managed non-surgically based on standard hospital clinical practice. Patients with MR who receive a pacemaker, Implantable Cardiac Defibrillator (ICD) and/or Cardiac Resynchronization Therapy (CRT) treatments may be included<br>|
| Mitral Valve Surgery<br>Patients with MR managed surgically (repair or replacement) based on standard hospital clinical practice. | Procedure: Mitral Valve Surgery<br>* The Mitral Valve Surgery Group consists of patients with MR in whom the MR is managed surgically (repair or replacement) based on standard hospital clinical practice. Patients with concurrent coronary artery bypass grafting (CABG) or aortic/tricuspid valve or and other cardiac procedure except atrial fibrillation surgery are excluded.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MR Severity | MR Severity: Site-assessed mitral regurgitation severity using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 1+ to 2+ is mild-to-moderate, 2+ to 3+ is moderate to moderate-to-Severe, 3+ is moderate-to-severe, 3+ to 4+ is moderate-to-severe to severe, 4+ is severe. MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. The Medical Therapy & Mitral Valve Surgery comparator groups were followed & studied primarily from a health economic perspective. Availability of clinical outcomes at followup is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported. | At baseline | 
| MR Severity | MR Severity: Site-assessed mitral regurgitation severity using echocardiography. MR severity is graded on a scale of 0+ to 4+ where 0+ means absence of mitral regurgitation, 1+ is mild, 1+ to 2+ is mild-to-moderate, 2+ to 3+ is moderate to moderate-to-Severe, 3+ is moderate-to-severe, 3+ to 4+ is moderate-to-severe to severe, 4+ is severe. MR severity was not consistently captured for patients in the Medical Management and Mitral Valve Surgery groups. The Medical Therapy & Mitral Valve Surgery comparator groups were followed & studied primarily from a health economic perspective. Availability of clinical outcomes at follow-up is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure Time | Procedure Time is defined as the time of start of the transseptal procedure to the time the Steerable Guide Catheter is removed. | Day 0 (On the day of procedure) | 
| Contrast Volume |  | Day 0 (On the day of procedure) | 
| Fluoroscopy Duration |  | Day 0 (On the day of procedure) | 
| Number of MitraClip Devices Implanted | Physicians had the option of deploying more than 1 MitraClip device if a single device did not provide satisfactory MR reduction, and if the mitral valve area was large enough to allow multiple MitraClip devices to be placed without causing mitral stenosis. | Day 0 (On the day of procedure) | 
| ICU and Hospital Stay | ICU and hospital stay is defined as the mean duration of time that patients spent in the ICU (Intensive Care Unit)/ CCU (Cardiac Care Unit)/ PACU (Post-Anesthesia Care Unit) following the MitraClip procedure. This secondary outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups. | From the day of procedure throughout 12 months of study period | 
| Discharge Status and Facility |  | At discharge, an average of 7.7 days following the MitraClip procedure | 
| Discharge MR Severity |  | At discharge, an average of 7.7 days following the MitraClip procedure | 
| Kaplan-Meier Freedom From All-Cause Mortality |  | At 0 day | 
| Kaplan-Meier Freedom From All-Cause Mortality |  | At 30 days | 
| Kaplan-Meier Freedom From All-Cause Mortality |  | At 6 months | 
| Kaplan-Meier Freedom From All-Cause Mortality |  | At 12 months | 
| Device Embolization and Single Leaflet Device Attachment | Device embolization is defined as bilateral Clip detachment resulting in Clip embolization. Reasons for Clip embolization include leaflet tearing, Clip unlocking, Clip fracture or inadequate Clip placement (i.e., malposition). Not included are any fractures or other failures of the Clip that do not result in Clip detachment from both leaflets. Single leaflet device attachment (SLDA) is defined as the loss of insertion of a single leaflet from the MitraClip device with ongoing insertion of the opposing leaflet. SLDAs are reported on ACCESS-EU adverse event log and MitraClip procedure electronic case report forms, and may also be reported by Abbott Vascular personnel per EU Vigilance requirements. | Through 12 months | 
| 1-Day Post-Procedure Safety Outcomes | This outcome measure does not apply to the Medical Management or the Mitral Valve Surgery groups. Because the Medical Therapy&Mitral Valve Surgery comparator groups were followed&studied primarily from a health economic perspective.Availability of clinical outcomes at follow-up is limited & has not been validated. Clinical outcomes for the comparator groups will not be reported. | On day 1 post procedure | 
| Need for Mitral Valve Surgery | This end point is assessed on subjects who underwent mitral valve surgery within 12 months post-MitraClip procedure. | Through 12 months | 
| NYHA Functional Class | New York Heart Association (NYHA) Functional Classification. Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest.Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest.Less than ordinary physical activity causes fatigue, palpitation dyspnea or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest.If any physical activity is undertaken,discomfort is increased. | At baseline | 
| NYHA Functional Class | Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status. Class I: Patients with cardiac disease but without resulting limitations of physical activity. Class II: Patients with cardiac disease resulting in slight limitation of physical activity.Patients are comfortable at rest.Ordinary physical activity results in fatigue, palpitation, dyspnea/anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity.They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea/anginal pain Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken,discomfort is increased. | At 12 month | 
| The Change in 6 Minute Walk Test Distance From Baseline to 12 Months | The 6 minute walk distance test will be used to measure the patient's exercise capacity. The change in 6 minute walk test distance is calculated as the difference between the distance walked at 12 months and the distanced walked at baseline. | Baseline and 12 months | 
| Change in Minnesota Living With Heart Failure (MLWHF) Quality of Life Score From Baseline to 12 Months | The Minnesota Living with Heart Failure Questionnaire(MLHFQ) is comprised of 21 questions.The response for each question ranges from 0(no affect on the patient's living) to 5(affected the patient's life very much during the past month).The total score for the 21 items can range from 0-105.A lower&higher MLHFQ score indicates less effect of heart failure&the worse impact of heart failure on a patient's QOL,respectively.Although the MLHFQ incorporates relevant aspects of the key dimensions of QOL (physical and emotional),the questionnaire was not designed to measure any particular dimension separately.The total score should be taken as the best measure of how heart failure and treatments impact QOL. The total score is the sum of a)the physical dimension,measured using 8 questions (possible subscale score range 0-40) b)the emotional dimension,measured using 5 questions(possible subscale score from 0-25)&c) other factors,measured using 8 questions (possible subscale score from 0-40). | 12 months | 
| Six Minute Walk Test Distance (6MWT) | The 6-minute walk distance test will be used to measure the patient's exercise capacity. | Baseline | 
| Six Minute Walk Test Distance (6MWT) | The 6-minute walk distance test will be used to measure the patient's exercise capacity. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitral Valve, Mitral Regurgitation, MitraClip, Mitral Valve Surgery, Mitral Valve Insufficiency or Mitral Regurgitation