Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement (COMPLETE TAVR)
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| ClinicalTrials.gov Identifier: NCT04634240 |
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Recruitment Status :
Recruiting
First Posted : November 18, 2020
Last Update Posted : April 8, 2022
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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) | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated 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 : | December 19, 2020 |
| Estimated Primary Completion Date : | April 1, 2026 |
| Estimated Study Completion Date : | April 1, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Complete Revascularization
Routine PCI (percutaneous coronary intervention) of all suitable coronary artery stenoses of ≥70% in vessels ≥2.5mm in diameter.
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Procedure: Percutaneous Coronary Intervention (PCI)
PCI of all qualifying lesions. |
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No Intervention: Medical Therapy Alone
No revascularization of coronary artery lesions.
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- 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 ]
- Cardiovascular Death or New Myocardial Infarction [ Time Frame: 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) [ Time Frame: Immediately post-TAVR ]
- Transaortic Gradient Reclassification [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]Includes deaths from both cardiac and non-cardiac causes
- Stroke [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Median follow-up of 3.5 years ]As evaluated by the Seattle Angina Questionnaire
- Economic evaluation [ Time Frame: Median follow-up of 3.5 years ]Includes health resource utilization, costs, and cost-effectiveness
- Patient-reported outcomes [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: During PCI procedure ]Total time under fluoroscopy
- Contrast Utilization for Stages PCI Procedure [ Time Frame: During PCI procedure ]
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04634240
| Contact: Brady J Robinson, CCRP | 604-875-4111 ext 22936 | brobinson@cci-cic.org |
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| Principal Investigator: | David A Wood, MD | CCI-CIC, University of British Columbia |
| Responsible Party: | David Wood, Professor, University of British Columbia |
| ClinicalTrials.gov Identifier: | NCT04634240 |
| Other Study ID Numbers: |
H20-00968 |
| First Posted: | November 18, 2020 Key Record Dates |
| Last Update Posted: | April 8, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Transcatheter Aortic Valve Replacement Percutaneous Coronary Intervention Coronary Artery Disease Aortic Stenosis |
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Coronary Artery Disease Myocardial Ischemia Coronary Disease Aortic Valve Stenosis Coronary Stenosis Constriction, Pathologic Heart Diseases Cardiovascular Diseases |
Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Pathological Conditions, Anatomical Aortic Valve Disease Heart Valve Diseases Ventricular Outflow Obstruction |