PARTNER trial

PARTNER trial
Name	PARTNER trial
Status	Completed
Phase	III
Condition	Aortic stenosis
Intervention	Transcatheter aortic valve replacement
Sponsor	Edwards Lifesciences
Start date	2007
Completion date	2015

PARTNER trial

The PARTNER trial was a multicenter randomized clinical trial that compared transcatheter aortic valve replacement with surgical aortic valve replacement and medical therapy for severe aortic stenosis in high‑risk and inoperable patients. Designed and overseen by academic investigators, regulatory agencies, device manufacturers, and guideline committees, the study influenced practice across cardiology, cardiac surgery, and health policy arenas. The trial's findings were cited in regulatory approvals, guideline updates, and subsequent device trials.

Background

Severe aortic stenosis had been managed primarily with surgical aortic valve replacement since innovations in cardiac surgery by figures associated with John Gibbon and institutions like Mayo Clinic and Cleveland Clinic. Advances in transcatheter techniques drew on catheterization developments at centers such as Mount Sinai Hospital and industry programs at Edwards Lifesciences and Medtronic. Early feasibility work, reported by teams affiliated with Columbia University, University of Maryland, and Bern University Hospital, led to multicenter collaboration and regulatory engagement with the Food and Drug Administration and the European Medicines Agency. Cardiothoracic and interventional societies including the American College of Cardiology and the European Society of Cardiology sought randomized evidence to inform guidelines and reimbursement decisions influenced by payers such as Centers for Medicare & Medicaid Services.

Trial Design and Methods

The trial comprised parallel randomized cohorts comparing transcatheter aortic valve replacement performed via transfemoral or transapical access with standard surgical aortic valve replacement or with medical therapy and balloon valvuloplasty in nonoperable patients. The protocol was developed by academic steering committees drawing members from Stanford University School of Medicine, Harvard Medical School, Johns Hopkins Hospital, and trial coordinating centers affiliated with Duke University Health System. Endpoints included all‑cause mortality, stroke, rehospitalization, and functional status measured by instruments used in trials at National Institutes of Health centers. Independent clinical events committees and core laboratories modeled after those used in cardiovascular trials at Brigham and Women's Hospital adjudicated outcomes, while data monitoring was overseen by a board with affiliations to University College London and Imperial College London.

Patient Population and Enrollment

Enrollees were older adults with symptomatic, severe calcific aortic stenosis deemed high surgical risk or inoperable by multidisciplinary heart teams including cardiac surgeons and interventional cardiologists from centers such as Massachusetts General Hospital, Penn Medicine, and Beth Israel Deaconess Medical Center. Baseline evaluation incorporated imaging from Mayo Clinic echocardiography laboratories and computed tomography protocols standardized with contributions from Johns Hopkins University radiology groups. Demographics reflected referrals from regional networks that included tertiary centers like UCLA Health and international sites in collaboration with European centers including Charité – Universitätsmedizin Berlin and Hôpital Européen Georges-Pompidou.

Outcomes and Results

Primary results reported that transcatheter aortic valve replacement reduced mortality compared with medical therapy in inoperable patients and provided survival comparable to surgery in high‑risk patients, with improvements in symptom scores and functional status similar to those seen in landmark trials conducted at institutions such as Cleveland Clinic and Royal Brompton Hospital. Ancillary analyses examined stroke rates, valve hemodynamics, and quality of life using instruments validated in cohorts from University of Oxford and University of Toronto. Publications in major journals prompted commentaries from editors at outlets with editorial boards including The New England Journal of Medicine and The Lancet and were discussed at scientific meetings such as the American Heart Association and the European Association for Cardio-Thoracic Surgery.

Safety and Complications

Safety signals included vascular complications associated with transfemoral access, conduction disturbances necessitating pacemaker implantation, and periprocedural stroke—issues observed in registries maintained by networks like Society of Thoracic Surgeons and National Cardiovascular Data Registry. Device‑related durability, paravalvular regurgitation, and bleeding events were prospectively monitored using adjudication processes modeled on trials at Vanderbilt University Medical Center and Mayo Clinic. Subsequent device iterations and operator training programs at centers such as University of Michigan and Imperial College London targeted reductions in these complications.

Impact and Clinical Significance

The trial reshaped guideline recommendations from bodies including the American College of Cardiology and the European Society of Cardiology, influenced regulatory clearances by the Food and Drug Administration and market access in regions governed by the European Medicines Agency, and catalyzed widespread adoption of transcatheter aortic valve replacement programs at hospitals like Mount Sinai Hospital and Cleveland Clinic. It stimulated comparative effectiveness research undertaken by groups at Duke University School of Medicine and policy analyses from think tanks associated with Harvard Kennedy School and payer organizations such as Centers for Medicare & Medicaid Services, and it spawned further randomized trials evaluating lower‑risk populations and new device platforms backed by manufacturers including Edwards Lifesciences and Medtronic.

Category:Cardiology clinical trials