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.
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.
Brief Title
Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
604-875-4111
Central Contact Phone Ext
22936
Central Contact Email
brobinson@cci-cic.org
Completion Date
Completion Date Type
Estimated
Conditions
Aortic Stenosis
Coronary Artery Disease
Coronary Stenosis
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
\- 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
Inclusion 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.
\- 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.
Gender
All
Gender Based
false
Keywords
Transcatheter Aortic Valve Replacement
Percutaneous Coronary Intervention
Coronary Artery Disease
Aortic Stenosis
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
NCT Id
NCT04634240
Org Class
Other
Org Full Name
University of British Columbia
Org Study Id
H20-00968
Overall Status
Recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Measure
Composite of Cardiovascular Death or New Myocardial Infarction or Ischemia-Driven Revascularization or Hospitalization for Unstable Angina or Heart Failure
Outcome Time Frame
Median follow-up of 3.5 years
Secondary Outcomes
Outcome Description
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.
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.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Cardiovascular Death or New Myocardial Infarction
Outcome Time Frame
Immediately post-TAVR
Outcome Measure
Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement)
Outcome Description
Proportion of patients developing echocardiographic aortic gradient ≥20 mmHg who are found to have a gradient \< 20 mmHg on direct hemodynamic assessment.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Transaortic Gradient Reclassification
Outcome Description
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.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
VARC-3 Hemodynamic Valve Deterioration Reclassification
Outcome Description
Proportion of patients with echocardiographic severe PPM immediately post-TAVR, reclassified as non-severe PPM using direct invasive methods.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Severe Patient Prosthesis Mismatch (PPM) Reclassification
Outcome Description
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.
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.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome 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
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Composite outcome of mean echocardiographic gradient ≥ 20mmHg, severe PPM, ≥ moderate AR, thrombosis, endocarditis, and aortic valve re-intervention
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Cardiovascular Death
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
New Myocardial Infarction
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Ischemia-Driven Revascularization
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Hospitalization for Unstable Angina or Heart Failure
Outcome Description
Includes deaths from both cardiac and non-cardiac causes
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
All-cause Mortality
Outcome Description
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.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Stroke
Outcome Description
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
* 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
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Bleeding
Outcome Description
As evaluated by the Seattle Angina Questionnaire
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Angina status
Outcome Description
Includes health resource utilization, costs, and cost-effectiveness
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Economic evaluation
Outcome Description
Health-related quality of life as evaluated by the Kansas City Cardiomyopathy Questionnaire at baseline, 30 days, 6 months, 1 year, and annually thereafter.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Patient-reported outcomes
Outcome Description
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.
Outcome Time Frame
Median follow-up of 3.5 years
Outcome Measure
Contrast-associated acute kidney injury
Outcome Description
Total time under fluoroscopy
Outcome Time Frame
During PCI procedure
Outcome Measure
Fluoroscopic time for Staged PCI procedure
Outcome Time Frame
During PCI procedure
Outcome Measure
Contrast Utilization for Stages PCI Procedure
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mark Menegus
Investigator Email
mmenegus@montefiore.org
Investigator Department
Medicine
Investigator Division
Cardiology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Cardiology
Categories Mesh Debug
Blood Disorders --- CORONARY ARTERY DISEASE
Heart/Cardiovascular --- CORONARY ARTERY DISEASE
Heart/Cardiovascular --- HEART VALVE DISEASES
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- MYOCARDIAL ISCHEMIA
Heart/Cardiovascular --- ARTERIOSCLEROSIS
Heart/Cardiovascular --- ARTERIAL OCCLUSIVE DISEASES
Blood & Bone Marrow Cancers --- VASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
MeSH Terms
AORTIC VALVE STENOSIS
CORONARY ARTERY DISEASE
CORONARY STENOSIS
AORTIC VALVE DISEASE
HEART VALVE DISEASES
HEART DISEASES
CARDIOVASCULAR DISEASES
VENTRICULAR OUTFLOW OBSTRUCTION
CORONARY DISEASE
MYOCARDIAL ISCHEMIA
ARTERIOSCLEROSIS
ARTERIAL OCCLUSIVE DISEASES
VASCULAR DISEASES
PERCUTANEOUS CORONARY INTERVENTION
ENDOVASCULAR PROCEDURES
VASCULAR SURGICAL PROCEDURES
CARDIOVASCULAR SURGICAL PROCEDURES
SURGICAL PROCEDURES, OPERATIVE
MINIMALLY INVASIVE SURGICAL PROCEDURES