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

Completed

• Conditions: Heart Valve Disease
• Interventions: Other: Decellularized human heart valves

• Registration Number: NCT02527629
• Lead Sponsor: corlife

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-07-27
• Study First Submitted QC: 2015-08-17
• Study First Posted: 2015-08-19
• Study Start: 2015-09
• Primary Completion: 2019-01
• Study Completion: 2019-03
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-29
• Last Update Posted: 2020-06-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

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®.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Decellularized human valves	Decellularized human heart valves	Aortic heart valve replacement

Primary Outcome Measures

Name	Time	Method
Freedom from valve dysfunction at end of the study	up to 24 months	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.
Cardiovascular Adverse Reactions (AR)	up to 24 months	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).

Secondary Outcome Measures

Name	Time	Method
Evaluation of composite blood parameters	up to 24 months	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.
Time to reoperation and / or death	up to 24 months	Time to events, such as death, reoperation including explantation will be evaluated for those outcomes, calculated from the date of operation
Evaluation of composite valve measures	up to 24 months	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.

Trial Locations

Locations (8)

University of Düsseldorf, Department of Cardiovascular Surgery; 🇩🇪 Düsseldorf, Germany

Royal Brompton and Harefield National Health Service Trust; 🇬🇧 London, United Kingdom

Universitair Ziekenhuis Leuven, UZL; 🇧🇪 Leuven, Belgium

University Hospital Clinic de Barcelona, Cardiovascular Surgery administrative area; 🇪🇸 Barcelona, Spain

Hannover Medical School; 🇩🇪 Hannover, Germany

Leids Universitair Medisch Centrum, LUMC; 🇳🇱 Leiden, Netherlands

Azienda Ospedaliera di Padova, U.O.C. di Cardiochirurgia Pediatrica e Cardiopatie Congenite; 🇮🇹 Padova, Italy

Kinderspital Zürich; 🇨🇭 Zürich, Switzerland