Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement

Official title

A Randomized, Comparative Effectiveness Study of Staged Complete Revascularization With Percutaneous Coronary Intervention to Treat Coronary Artery Disease vs Medical Management Alone in Patients With Symptomatic Aortic Valve Stenosis Undergoing Elective Transfemoral Transcatheter Aortic Valve Replacement: The COMPLETE TAVR Study

Overview

Patients undergoing transcatheter aortic valve replacement (TAVR) often have concomitant coronary artery disease (CAD) which may adversely affect prognosis. There is uncertainty about the benefits and the optimal timing of revascularization for such patients. There is currently clinical equipoise regarding the management of concomitant CAD in patients undergoing TAVR. Some centers perform routine revascularization with percutaneous coronary intervention (PCI) (either before or after TAVR), while others follow an alternative strategy of medical management. The potential benefits and optimal timing of PCI in these patients are unknown. As TAVR expands to lower risk patients, and potentially becomes the preferred therapy for the majority of patients with severe aortic stenosis, the optimal management of concomitant coronary artery disease will be of increasing importance. The COMPLETE TAVR study will determine whether, on a background of guideline-directed medical therapy, a strategy of complete revascularization involving staged PCI using drug eluting stents to treat all suitable coronary artery lesions is superior to a strategy of medical therapy alone in reducing the composite outcome of Cardiovascular Death, new Myocardial Infarction, Ischemia-driven Revascularization or Hospitalization for Unstable Angina or Heart Failure. The study will be a randomized, multicenter, open-label trial with blinded adjudication of outcomes. Patients will be screened and consented for elective transfemoral TAVR and randomized within 96 hours of successful balloon expandable TAVR. Complete Revascularization: Staged PCI using third generation drug eluting stents to treat all suitable coronary artery lesions in vessels that are at least 2.5 mm in diameter and that are amenable to treatment with PCI and have a ≥70% visual angiographic diameter stenosis. Staged PCI can occur any time from 1 to 45 days post successful transfemoral TAVR. Vs. Medical Therapy Alone: No further revascularization of coronary artery lesions. All patients, regardless of randomized treatment allocation, will receive guideline-directed medical therapy consisting of risk factor modification and use of evidence-based therapies. The COMPLETE TAVR study will help address the current lack of evidence in this area. It will likely impact both the global delivery of health care and the management and clinical outcomes of all patients undergoing TAVR with concomitant CAD.

Interventions

• Procedure Percutaneous Coronary Intervention (PCI)
  PCI of all qualifying lesions.

Primary outcome measures

• Composite of Cardiovascular Death or New Myocardial Infarction or Ischemia-Driven Revascularization or Hospitalization for Unstable Angina or Heart Failure [Time frame: Median follow-up of 3.5 years]

Secondary outcome measures (12)

• Cardiovascular Death or New Myocardial Infarction [Time frame: Median follow-up of 3.5 years]
• Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement) [Time frame: Immediately post-TAVR]
• Transaortic Gradient Reclassification [Time frame: Median follow-up of 3.5 years]
• VARC-3 Hemodynamic Valve Deterioration Reclassification [Time frame: Median follow-up of 3.5 years]
• Severe Patient Prosthesis Mismatch (PPM) Reclassification [Time frame: Median follow-up of 3.5 years]
• Composite of CV Death, New MI, IDR or Hospitalization for UA or for HF in patients with PPM and elevated gradients vs those without [Time frame: Median follow-up of 3.5 years]
• Composite outcome of mean echocardiographic gradient ≥ 20mmHg, severe PPM, ≥ moderate AR, thrombosis, endocarditis, and aortic valve re-intervention [Time frame: Median follow-up of 3.5 years]
• Cardiovascular Death [Time frame: Median follow-up of 3.5 years]
• New Myocardial Infarction [Time frame: Median follow-up of 3.5 years]
• Ischemia-Driven Revascularization [Time frame: Median follow-up of 3.5 years]
• Hospitalization for Unstable Angina or Heart Failure [Time frame: Median follow-up of 3.5 years]
• All-cause Mortality [Time frame: Median follow-up of 3.5 years]

Eligibility criteria

Inclusion criteria

\- Symptomatic aortic valve stenosis prior to TAVR (NYHA Functional Class ≥ 2 OR Abnormal exercise test with severe SOB, abnormal BP response, or arrhythmia)

AND

\- CAD defined as: at least 1 coronary artery lesion of ≥70% visual angiographic diameter stenosis in a native segment ≥2.5 mm in diameter that is not a CTO and is amenable to treatment with PCI

AND

\- Consensus by the Local Multidisciplinary Heart Team that the patient is suitable for elective transfemoral TAVR with a balloon expandable transcatheter heart valve AND would receive a bypass with an anastomosis distal to the coronary artery lesion(s) if they were undergoing SAVR.

Local Multidisciplinary Heart Teams are expected to follow current clinical guidelines for selection of patients for TAVR with an eligible patient generally expected to have:

\[AVA ≤ 1.0 cm2 OR AVA index ≤ 0.6 cm2/m2\]

OR

\[Jet velocity ≥ 4.0 m/s OR mean gradient ≥ 40 mmHg\]

OR

patients without these criteria may undergo TAVR if the Local Multidisciplinary Heart Team concludes it is appropriate.

AND

\- Successful transfemoral TAVR, defined as the implantation of a single transcatheter aortic valve within the past 96 hours with freedom from more than minimal aortic insufficiency, stroke, or major vascular complications.

Exclusion criteria

• PCI already performed within 90 days prior to TAVR or at the same time as the index transfemoral TAVR procedure
• Planned PCI of coronary artery lesion(s)
• Planned surgical revascularization of coronary artery lesion(s)
• Non-cardiovascular co-morbidity reducing life expectancy to < 5 years
• Any factor precluding 5-year follow-up
• Prior coronary artery bypass grafting surgery or surgical valve replacement
• Severe mitral regurgitation (> 3+)
• Severe left ventricular dysfunction (LVEF < 30%)
• Low coronary takeoff (high risk for coronary obstruction)
• Acute myocardial infarction within 90 days
• Stroke or transient ischemic attack within 90 days
• Renal insufficiency (eGFR < 30 ml/min) and/or renal replacement Rx
• Hemodynamic or respiratory instability

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 55 centers

• Huntsville Heart Center — Huntsville
• Arizona Cardiovascular Research — Phoenix
• Veteran Affairs Palo Alto Health Care System — Palo Alto
• Loma Linda University — Redlands
• Santa Barbara Cottage Hospital — Santa Barbara
• Torrance Memorial Medical Center — Torrance
• JFK Medical Center — Atlantis
• Baptist Health Jacksonville — Jacksonville
• … and 47 more centers

Canada · 17 centers

• University of Alberta, Mazankowski Heart Institute — Edmonton
• Royal Columbian Hospital — New Westminster
• Vancouver General Hospital — Vancouver
• Centre for Cardiovascular Innovation-Centre d'Innovation Cardiovasculaire (CCI-CIC) — Vancouver
• St. Paul's Hospital — Vancouver
• Saint Boniface — Winnipeg
• New Brunswick Heart — Saint John
• Queen Elizabeth II Health Sciences Centre — Halifax
• … and 9 more centers

Identifiers

NCT: NCT04634240 · H20-00968

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗