Clinical trial NCT04634240: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Stenosis
Coronary Artery Disease
Coronary Stenosis
Keywords: Transcatheter Aortic Valve Replacement
Percutaneous Coronary Intervention
Coronary Artery Disease
Aortic Stenosis
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2020-11-18
Enrollment: 4000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Composite of Cardiovascular Death or New Myocardial Infarction or Ischemia-Driven Revascularization or Hospitalization for Unstable Angina or Heart Failure
timeFrame: Median follow-up of 3.5 years
Secondary outcomes:
measure: Cardiovascular Death or New Myocardial Infarction
timeFrame: Median follow-up of 3.5 years
measure: Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement)
timeFrame: Immediately post-TAVR
measure: Transaortic Gradient Reclassification
timeFrame: Median follow-up of 3.5 years
measure: VARC-3 Hemodynamic Valve Deterioration Reclassification
timeFrame: Median follow-up of 3.5 years
measure: Severe Patient Prosthesis Mismatch (PPM) Reclassification
timeFrame: Median follow-up of 3.5 years
measure: Composite of CV Death, New MI, IDR or Hospitalization for UA or for HF in patients with PPM and elevated gradients vs those without
timeFrame: Median follow-up of 3.5 years
measure: Composite outcome of mean echocardiographic gradient ≥ 20mmHg, severe PPM, ≥ moderate AR, thrombosis, endocarditis, and aortic valve re-intervention
timeFrame: Median follow-up of 3.5 years
measure: Cardiovascular Death
timeFrame: Median follow-up of 3.5 years
measure: New Myocardial Infarction
timeFrame: Median follow-up of 3.5 years
measure: Ischemia-Driven Revascularization
timeFrame: Median follow-up of 3.5 years
measure: Hospitalization for Unstable Angina or Heart Failure
timeFrame: Median follow-up of 3.5 years
measure: All-cause Mortality
timeFrame: Median follow-up of 3.5 years
measure: Stroke
timeFrame: Median follow-up of 3.5 years
measure: Bleeding
timeFrame: Median follow-up of 3.5 years
measure: Angina status
timeFrame: Median follow-up of 3.5 years
measure: Economic evaluation
timeFrame: Median follow-up of 3.5 years
measure: Patient-reported outcomes
timeFrame: Median follow-up of 3.5 years
measure: Contrast-associated acute kidney injury
timeFrame: Median follow-up of 3.5 years
measure: Fluoroscopic time for Staged PCI procedure
timeFrame: During PCI procedure
measure: Contrast Utilization for Stages PCI Procedure
timeFrame: During PCI procedure
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Huntsville Heart Center
state: Alabama
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research
state: Arizona
city: Palo Alto
country: United States
facility: Veteran Affairs Palo Alto Health Care System
state: California
city: Redlands
country: United States
facility: Loma Linda University
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Health Jacksonville
state: Florida
city: Miami
country: United States
facility: Miami Cardiac and Vascular/Baptist Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Health System
state: Georgia
city: Boise
country: United States
facility: St. Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Ascension Alexian Brothers
state: Illinois
city: Elkhart
country: United States
facility: Midwest Cardiovascular Research and Education Foundation
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Midwest Heart and Vascular
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Boston
country: United States
facility: Tufts Medical
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saginaw
country: United States
facility: Ascension St. Mary's
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Heart and Vascular Center
state: Minnesota
city: Columbia
country: United States
facility: Boone Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist
state: Missouri
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Our Lady of Lourdes
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Mineola
country: United States
facility: NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: St. Joseph's Hospital
state: New York
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular Institute
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Heart
state: Oklahoma
city: Clackamas
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Germantown
country: United States
facility: Methodist Le Bonheur Healthcare
state: Tennessee
city: Kingsport
country: United States
facility: Ballad Health CVA Heart Institute
state: Tennessee
city: Knoxville
country: United States
facility: Parkwest Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Cardiovascular Surgery Clinic/Baptist Memorial
state: Tennessee
city: Houston
country: United States
facility: HCA Houston Healthcare Medical Center
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Plano
state: Texas
city: Round Rock
country: United States
facility: Baylor Scott & White Round Rock
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Green Bay
country: United States
facility: Bellin Health System
state: Wisconsin
city: Milwaukee
country: United States
facility: Ascension Columbia St. Mary's
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta, Mazankowski Heart Institute
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Centre for Cardiovascular Innovation-Centre d'Innovation Cardiovasculaire (CCI-CIC)
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Saint Boniface
state: Manitoba
city: Saint John
country: Canada
facility: New Brunswick Heart
state: New Brunswick
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montréal
country: Canada
facility: Montréal Heart
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Sacré-Coeur
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie-CHUS
state: Quebec
city: Regina
country: Canada
facility: Prairie Vascular
state: Saskatchewan
Study officials:
affiliation: CCI-CIC, University of British Columbia
name: David A Wood, MD
role: PRINCIPAL_INVESTIGATOR
References: