Aortic Replacement Using Individualised Regenerative Allografts - ARISE (the Surveillance)

Study Overview
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Brief Summary
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Evaluation of decellularized human heart valves for aortic heart valve replacement in comparison to current valve substitutes. Safety endpoints include cardiovascular adverse events, time to re-operation, re-intervention and explantation. Efficacy endpoints include freedom from valve dysfunction and hemodynamic performance.

Detailed Description
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This is a prospective, non-randomized, single-arm, multi-centre surveillance study to be conducted in Europe. The Surveillance is designed as a study, where ARISE AV is prescribed in the usual manner in accordance with the terms of the approval. Assignment of the patient to a particular therapeutic strategy is not decided in advance by this Surveillance Protocol but falls within current practice and the prescription of ARISE AV is clearly separated from the decision to include the patient in the Surveillance. No additional diagnostic or monitoring procedures shall be applied to the patients. and epidemiological methods shall be used for the analysis of collected data.

Official Title
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Aortic Replacement Using Individualised Regenerative Allografts: Bridging the Therapeutic Gap - ARISE (the Surveillance)

Conditions
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Heart Valve Disease

Intervention / Treatment
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* Other: Decellularized human heart valves


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: i. Indication for aortic valve replacement according to current medical guidelines in valvular heart disease ii. Informed consent of legal guardians or patients, assent of patients Exclusion Criteria: i. The patient has not provided Surveillance informed consent. ii. The patient shall not suffer from: generalized connective tissue disorders (eg, Marfan syndrome), or . active rheumatic disorders, or severe asymmetric calcification of the valve ring. iii. The coronary arteries of the patient shall not be in abnormal position or heavily calcified. iv. Patients shall not show hypersensitivity against sodium dodecyl sulphate (SDS), sodium desoxycholate (SDC), human collagen (or other elastic fibers) or Benzonase®.
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 |
| --- | --- |
| Decellularized human valves<br>Aortic heart valve replacement | Other: Decellularized human heart valves<br>* Decellularized human aortic heart valves<br>* Other names: Arise Aortic Valve (AV);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Adverse Reactions (AR) | Rate of cardiovascular AR, e.g. all-cause mortality, major stroke, life-threatening (or disabling) bleeding, acute kidney injury-stage 3 (including renal replacement therapy), peri-procedural myocardial infarction, major vascular complication, repeat procedure for valve-related dysfunction (surgical or interventional therapy). | up to 24 months | 
| Freedom from valve dysfunction at end of the study | Echocardiographic studies should be obtained and analyzed at discharge and at 3, 6 Months and at annual follow-ups. The requested variables include peak and mean systolic gradient, using pw and cw doppler, in the left ventricular outflow tract, respective the aortic valve. The echo evaluation (videotape or CD) should remain at the Surveillance site, but be available to corlife Surveillance personnel upon request. The MRIs will be analyzed by the MRI Core Laboratory at Medical School in Hannover for potential valvular stenosis, via phase contrast flow measurements in the aorta and for valvular competence, via phase contrast flow measurements and by ventricular volumetry. MRI cine images will be used to visualize the Surveillance valve in patients with poor echocardiographic windows. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of composite blood parameters | The following data should be collected: Hb, LDH, Haptoglobin, CRP, Leukocytes. Blood studies should be performed within 7 days preoperatively and at discharge. Blood data will support the absence/presence of related AR. For example, haemolysis should be reported as an adverse event if anaemia is present; however, in the absence of anaemia, haemolysis will be considered to be compensated and does not require reporting. Time to events, such as death, reoperation including explantation will be evaluated for those outcomes, calculated from the date of operation. | up to 24 months | 
| Time to reoperation and / or death | Time to events, such as death, reoperation including explantation will be evaluated for those outcomes, calculated from the date of operation | up to 24 months | 
| Evaluation of composite valve measures | Diameters of ARISE AV at end of the Surveillance will be analyzed in comparison to diameters at implantation and to age matched reference values. Preoperative non-invasive data on left ventricular size and function, such as left ventricular end diastolic, end systolic volume, ejection fraction and ventricular mass will be derived from MRI and compared to postoperative status. | up to 24 months |