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

Sponsor

University of British Columbia (Other)

Overall Status

Recruiting

CT.gov ID

NCT04634240

Collaborator

(none)

4,000

Enrollment

Locations

Arms

63.4

Anticipated Duration (Months)

153.8

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Stenosis Coronary Artery Disease Coronary Stenosis	Procedure: Percutaneous Coronary Intervention (PCI)	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 19, 2020

Anticipated Primary Completion Date :

Apr 1, 2026

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Complete Revascularization Routine PCI (percutaneous coronary intervention) of all suitable coronary artery stenoses of ≥70% in vessels ≥2.5mm in diameter.	Procedure: Percutaneous Coronary Intervention (PCI) PCI of all qualifying lesions.
No Intervention: Medical Therapy Alone No revascularization of coronary artery lesions.

Arm

Intervention/Treatment

Experimental: Complete Revascularization

Routine PCI (percutaneous coronary intervention) of all suitable coronary artery stenoses of ≥70% in vessels ≥2.5mm in diameter.

Procedure: Percutaneous Coronary Intervention (PCI)

PCI of all qualifying lesions.

No Intervention: Medical Therapy Alone

No revascularization of coronary artery lesions.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Cardiovascular Death or New Myocardial Infarction [Median follow-up of 3.5 years]
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.
Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement) [Immediately post-TAVR]
Transaortic Gradient Reclassification [Median follow-up of 3.5 years]
Proportion of patients developing echocardiographic aortic gradient ≥20 mmHg who are found to have a gradient < 20 mmHg on direct hemodynamic assessment.
VARC-3 Hemodynamic Valve Deterioration Reclassification [Median follow-up of 3.5 years]
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.
Severe Patient Prosthesis Mismatch (PPM) Reclassification [Median follow-up of 3.5 years]
Proportion of patients with echocardiographic severe PPM immediately post-TAVR, reclassified as non-severe PPM using direct invasive methods.
Composite of CV Death, New MI, IDR or Hospitalization for UA or for HF in patients with PPM and elevated gradients vs those without [Median follow-up of 3.5 years]
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.
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]
Cardiovascular Death [Median follow-up of 3.5 years]
New Myocardial Infarction [Median follow-up of 3.5 years]
Ischemia-Driven Revascularization [Median follow-up of 3.5 years]
Hospitalization for Unstable Angina or Heart Failure [Median follow-up of 3.5 years]
All-cause Mortality [Median follow-up of 3.5 years]
Includes deaths from both cardiac and non-cardiac causes
Stroke [Median follow-up of 3.5 years]
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.
Bleeding [Median follow-up of 3.5 years]
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
Angina status [Median follow-up of 3.5 years]
As evaluated by the Seattle Angina Questionnaire
Economic evaluation [Median follow-up of 3.5 years]
Includes health resource utilization, costs, and cost-effectiveness
Patient-reported outcomes [Median follow-up of 3.5 years]
Health-related quality of life as evaluated by the Kansas City Cardiomyopathy Questionnaire at baseline, 30 days, 6 months, 1 year, and annually thereafter.
Contrast-associated acute kidney injury [Median follow-up of 3.5 years]
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.
Fluoroscopic time for Staged PCI procedure [During PCI procedure]
Total time under fluoroscopy
Contrast Utilization for Stages PCI Procedure [During PCI procedure]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women with severe symptomatic aortic valve stenosis defined as: [aortic valve area ≤ 1.0 cm2 or aortic valve area index ≤ 0.6 cm2/m2] AND [Jet velocity ≥ 4.0 m/s or mean gradient ≥ 40 mmHg] AND [NYHA Functional Class ≥ 2 OR abnormal exercise test with severe SOB, abnormal blood pressure response, or arrhythmia]

AND

Coronary artery disease defined as: (at least 1 coronary artery lesion of ≥70% visual angiographic diameter stenosis in a native segment that is at least 2.5 mm in diameter that is not a CTO and is amenable to treatment with percutaneous coronary intervention (PCI))

AND

Consensus by the Multidisciplinary Heart Team that the patient is suitable for elective transfemoral transcatheter aortic valve replacement (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 surgical aortic valve replacement.

AND

Successful 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Huntsville Heart Center	Huntsville	Alabama	United States	35801
2	Veteran Affairs Palo Alto Health Care System	Palo Alto	California	United States	94304
3	Emory University Hospital	Atlanta	Georgia	United States	30308
4	St. Alphonsus Regional Medical Center	Boise	Idaho	United States	83709
5	Parkview Research Center	Fort Wayne	Indiana	United States	46845
6	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
7	St. Joseph Mercy Health System	Ypsilanti	Michigan	United States	48197
8	University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455
9	CentraCare Heart and Vascular Center	Saint Cloud	Minnesota	United States	56303
10	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03765
11	University at Buffalo	Buffalo	New York	United States	14203
12	NYU Langone Hospital - Long Island	Mineola	New York	United States	11501
13	Columbia University Medical Center	New York	New York	United States	10552
14	St. Joseph's Hospital	Syracuse	New York	United States	13088
15	Novant Health Heart and Vascular Institute	Charlotte	North Carolina	United States	28204
16	Summa Health System	Akron	Ohio	United States	44304
17	Rhode Island Hospital	Providence	Rhode Island	United States	02903
18	Methodist Le Bonheur Healthcare	Germantown	Tennessee	United States	38138
19	Parkwest Medical Center	Knoxville	Tennessee	United States	37923
20	University of Alberta, Mazankowski Heart Institute	Edmonton	Alberta	Canada	T6G 2B7
21	Royal Columbian Hospital	New Westminster	British Columbia	Canada	V3L 3W7
22	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
23	Centre for Cardiovascular Innovation-Centre d'Innovation Cardiovasculaire (CCI-CIC)	Vancouver	British Columbia	Canada	V5Z1M9
24	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
25	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8L 2X2
26	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8