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

Coronary Artery Disease Clinical Trial

— COMPLETE TAVR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04634240
• Other study ID #: H20-00968
• Status: Recruiting
• Phase: N/A
• Start date: December 19, 2020
• Est. completion date: April 1, 2026

Study information

• Verified date: December 2023
• Source: University of British Columbia
• Contact: Brady J Robinson, CCRP
• Phone: 604-875-4111
• Email: brobinson[@]cci-cic.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Constriction, Pathologic
• Coronary Artery Disease
• Coronary Disease
• Coronary Stenosis
• Myocardial Ischemia

Intervention

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

Locations

Country	Name	City	State
Canada	University of Alberta, Mazankowski Heart Institute	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Montréal Heart	Montréal	Quebec
Canada	Sacré-Coeur	Montréal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Ottawa Heart	Ottawa	Ontario
Canada	Prairie Vascular	Regina	Saskatchewan
Canada	New Brunswick Heart	Saint John	New Brunswick
Canada	CIUSSS de l'Estrie-CHUS	Sherbrooke	Quebec
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Hospital	Toronto	Ontario
Canada	Centre for Cardiovascular Innovation-Centre d'Innovation Cardiovasculaire (CCI-CIC)	Vancouver	British Columbia
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Saint Boniface	Winnipeg	Manitoba
United States	Summa Health System	Akron	Ohio
United States	Piedmont	Atlanta	Georgia
United States	JFK Medical Center	Atlantis	Florida
United States	St. Alphonsus Regional Medical Center	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University at Buffalo	Buffalo	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Our Lady of Lourdes	Camden	New Jersey
United States	Novant Health Heart and Vascular Institute	Charlotte	North Carolina
United States	Ascension Alexian Brothers	Chicago	Illinois
United States	Kaiser Permanente Northwest	Clackamas	Oregon
United States	Boone Hospital	Columbia	Missouri
United States	Mount Carmel	Columbus	Ohio
United States	Midwest Cardiovascular Research and Education Foundation	Elkhart	Indiana
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Northeast Georgia Health System	Gainesville	Georgia
United States	Methodist Le Bonheur Healthcare	Germantown	Tennessee
United States	Bellin Health System	Green Bay	Wisconsin
United States	HCA Houston Healthcare Medical Center	Houston	Texas
United States	Huntsville Heart Center	Huntsville	Alabama
United States	Baptist Health Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Ballad Health CVA Heart Institute	Kingsport	Tennessee
United States	Parkwest Medical Center	Knoxville	Tennessee
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Bryan Heart	Lincoln	Nebraska
United States	Cardiovascular Surgery Clinic/Baptist Memorial	Memphis	Tennessee
United States	Miami Cardiac and Vascular/Baptist Hospital	Miami	Florida
United States	Ascension Columbia St. Mary's	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai	New York	New York
United States	Oklahoma Heart	Oklahoma City	Oklahoma
United States	Midwest Heart and Vascular	Overland Park	Kansas
United States	Veteran Affairs Palo Alto Health Care System	Palo Alto	California
United States	Arizona Cardiovascular Research	Phoenix	Arizona
United States	Baylor Scott & White Plano	Plano	Texas
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Loma Linda University	Redlands	California
United States	Valley Hospital	Ridgewood	New Jersey
United States	Baylor Scott & White Round Rock	Round Rock	Texas
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Ascension St. Mary's	Saginaw	Michigan
United States	CentraCare Heart and Vascular Center	Saint Cloud	Minnesota
United States	Missouri Baptist	Saint Louis	Missouri
United States	St. Louis University	Saint Louis	Missouri
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	St. Joseph's Hospital	Syracuse	New York
United States	Torrance Memorial Medical Center	Torrance	California
United States	Cardiovascular Research Institute of Kansas	Wichita	Kansas
United States	St. Joseph Mercy Health System	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Cardiovascular Death or New Myocardial Infarction or Ischemia-Driven Revascularization or Hospitalization for Unstable Angina or Heart Failure		Median follow-up of 3.5 years
Secondary	Cardiovascular Death or New Myocardial Infarction	Deaths will be classified as cardiovascular or non-cardiovascular. All deaths with a clear cardiovascular or unknown cause, will be classified as cardiovascular. However, within cardiovascular deaths, hemorrhagic deaths will be clearly identified. Only deaths due to a documented non-cardiovascular cause (e.g., cancer) will be classified as non-cardiovascular.; Myocardial Infarction will be defined according to the 4th Universal Definition of Myocardial Infarction, with modification for Type 4a (PCI-related) and Type 5 (CABG-related) as defined for the ISCHEMIA trial and as used in the COMPLETE trial.	Median follow-up of 3.5 years
Secondary	Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement)		Immediately post-TAVR
Secondary	Transaortic Gradient Reclassification	Proportion of patients developing echocardiographic aortic gradient =20 mmHg who are found to have a gradient < 20 mmHg on direct hemodynamic assessment.	Median follow-up of 3.5 years
Secondary	VARC-3 Hemodynamic Valve Deterioration Reclassification	Proportion of patients developing = moderate echocardiographic VARC-3 valve deterioration reclassified to < moderate VARC-3 valve deterioration using direct invasive methods, including mean gradient and valve area.	Median follow-up of 3.5 years
Secondary	Severe Patient Prosthesis Mismatch (PPM) Reclassification	Proportion of patients with echocardiographic severe PPM immediately post-TAVR, reclassified as non-severe PPM using direct invasive methods.	Median follow-up of 3.5 years
Secondary	Composite of CV Death, New MI, IDR or Hospitalization for UA or for HF in patients with PPM and elevated gradients vs those without	Deaths: will be classified as cardiovascular or non-cardiovascular. All deaths with a clear cardiovascular or unknown cause, will be classified as cardiovascular. However, within cardiovascular deaths, hemorrhagic deaths will be clearly identified. Only deaths due to a documented non-cardiovascular cause (e.g., cancer) will be classified as non-cardiovascular.; Myocardial Infarction: will be defined according to the 4th Universal Definition of Myocardial Infarction, with modification for Type 4a (PCI-related) and Type 5 (CABG-related) as defined for the ISCHEMIA trial and as used in the COMPLETE trial.; Hospital admission: for protocol-defined unstable angina, new/worsening NYHA Class IV heart failure, or for protocol-defined Ischemia-driven revascularization, among patients with patient prosthesis mismatch (PPM), elevated echocardiography-derived transaortic gradients and elevated direct invasive transaortic gradient vs those without.	Median follow-up of 3.5 years
Secondary	Composite outcome of mean echocardiographic gradient = 20mmHg, severe PPM, = moderate AR, thrombosis, endocarditis, and aortic valve re-intervention		Median follow-up of 3.5 years
Secondary	Cardiovascular Death		Median follow-up of 3.5 years
Secondary	New Myocardial Infarction		Median follow-up of 3.5 years
Secondary	Ischemia-Driven Revascularization		Median follow-up of 3.5 years
Secondary	Hospitalization for Unstable Angina or Heart Failure		Median follow-up of 3.5 years
Secondary	All-cause Mortality	Includes deaths from both cardiac and non-cardiac causes	Median follow-up of 3.5 years
Secondary	Stroke	Defined as the presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting more than 24 hours. It is strongly recommended (but not required) that an imaging procedure such as CT scan or MRI be performed. Stroke will be further classified as ischemic, hemorrhagic or type uncertain.	Median follow-up of 3.5 years
Secondary	Bleeding	Clinically overt, symptomatic bleeding with at least one of the following criteria: Fatal, or; Symptomatic intracranial hemorrhage, or; Retroperitoneal hemorrhage, or; Intraocular hemorrhage leading to significant vision loss, or; Decrease in hemoglobin of 3.0 g/dL (with each blood transfusion unit counting for 1.0 g/dL of Hb) or requiring transfusion of two or more units of red blood cells or equivalent of whole blood.; Requiring surgical intervention to stop the bleeding	Median follow-up of 3.5 years
Secondary	Angina status	As evaluated by the Seattle Angina Questionnaire	Median follow-up of 3.5 years
Secondary	Economic evaluation	Includes health resource utilization, costs, and cost-effectiveness	Median follow-up of 3.5 years
Secondary	Patient-reported outcomes	Health-related quality of life as evaluated by the Kansas City Cardiomyopathy Questionnaire at baseline, 30 days, 6 months, 1 year, and annually thereafter.	Median follow-up of 3.5 years
Secondary	Contrast-associated acute kidney injury	An absolute rise in serum creatinine of greater than or equal to 44 µmol/L from baseline and/or a relative rise in serum creatinine of =25% compared to baseline at any time between 48hrs and 96hrs post-procedure.	Median follow-up of 3.5 years
Secondary	Fluoroscopic time for Staged PCI procedure	Total time under fluoroscopy	During PCI procedure
Secondary	Contrast Utilization for Stages PCI Procedure		During PCI procedure