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

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Valve Disease
• Intervention / Treatment: Other: Decellularized human heart valves

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 Type: Observational
• Enrollment (Actual): 144

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven, UZL
• Germany
  • Düsseldorf, Germany, 40225
    • University of Düsseldorf, Department of Cardiovascular Surgery
  • Hannover, Germany, 30625
    • Hannover Medical School
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova, U.O.C. di Cardiochirurgia Pediatrica e Cardiopatie Congenite
• Netherlands
  • Leiden, Netherlands, 2333
    • Leids Universitair Medisch Centrum, LUMC
• Spain
  • Barcelona, Spain, 08036
    • University Hospital Clinic de Barcelona, Cardiovascular Surgery administrative area
• Switzerland
  • Zürich, Switzerland, 8032
    • Kinderspital Zürich
• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Royal Brompton and Harefield National Health Service Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe aortic valve disease and the indication for aortic valve replacement

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Decellularized human valves; Aortic heart valve replacement	Other: Decellularized human heart valves; Decellularized human aortic heart valves; Other Names: Arise Aortic Valve (AV)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: corlife
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Hannover Medical School; Hospital Clinic of Barcelona; Heinrich-Heine University, Duesseldorf; Azienda Ospedaliera di Padova; Royal Brompton & Harefield NHS Foundation Trust; Leiden University Medical Center; Vienna General Hospital

Publications and helpful links

General Publications

• Horke A, Tudorache I, Laufer G, Andreas M, Pomar JL, Pereda D, Quintana E, Sitges M, Meyns B, Rega F, Hazekamp M, Hubler M, Schmiady M, Pepper J, Rosendahl U, Lichtenberg A, Akhyari P, Jashari R, Boethig D, Bobylev D, Avsar M, Cebotari S, Haverich A, Sarikouch S. Early results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement: the ARISE study and ARISE Registry data. Eur J Cardiothorac Surg. 2020 Nov 1;58(5):1045-1053. doi: 10.1093/ejcts/ezaa100.

Helpful Links

• ARISE Website

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: August 17, 2015
• First Posted (Estimate): August 19, 2015

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 29, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases
• Other Study ID Numbers: 2015- 01, 20.07.2015; Grant Agreement No: 643597 (Other Grant/Funding Number: European Commission)

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study results