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

תקציר

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.

זכאות

תכנון המחקר

מדדי תוצאה

1. מדד תוצאה ראשוני

   Composite of Cardiovascular Death or New Myocardial Infarction or Ischemia-Driven Revascularization or Hospitalization for Unstable Angina or Heart Failure

   מסגרת זמן Median follow-up of 3.5 years

2. מדד תוצאה משני

   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.

   מסגרת זמן Median follow-up of 3.5 years

3. מדד תוצאה משני

   Transaortic gradient immediately post-TAVR (echocardiographically-derived vs. direct invasive measurement)

   מסגרת זמן Immediately post-TAVR

4. מדד תוצאה משני

   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.

   מסגרת זמן Median follow-up of 3.5 years

5. מדד תוצאה משני

   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.

   מסגרת זמן Median follow-up of 3.5 years

6. מדד תוצאה משני

   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.

   מסגרת זמן Median follow-up of 3.5 years

7. מדד תוצאה משני

   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.

   מסגרת זמן Median follow-up of 3.5 years

8. מדד תוצאה משני

   Composite outcome of mean echocardiographic gradient ≥ 20mmHg, severe PPM, ≥ moderate AR, thrombosis, endocarditis, and aortic valve re-intervention

   מסגרת זמן Median follow-up of 3.5 years

9. מדד תוצאה משני

   Cardiovascular Death

   מסגרת זמן Median follow-up of 3.5 years

10. מדד תוצאה משני

    New Myocardial Infarction

    מסגרת זמן Median follow-up of 3.5 years

11. מדד תוצאה משני

    Ischemia-Driven Revascularization

    מסגרת זמן Median follow-up of 3.5 years

12. מדד תוצאה משני

    Hospitalization for Unstable Angina or Heart Failure

    מסגרת זמן Median follow-up of 3.5 years

13. מדד תוצאה משני

    All-cause Mortality

    Includes deaths from both cardiac and non-cardiac causes

    מסגרת זמן Median follow-up of 3.5 years

14. מדד תוצאה משני

    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.

    מסגרת זמן Median follow-up of 3.5 years

15. מדד תוצאה משני

    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

    מסגרת זמן Median follow-up of 3.5 years

16. מדד תוצאה משני

    Angina status

    As evaluated by the Seattle Angina Questionnaire

    מסגרת זמן Median follow-up of 3.5 years

17. מדד תוצאה משני

    Economic evaluation

    Includes health resource utilization, costs, and cost-effectiveness

    מסגרת זמן Median follow-up of 3.5 years

18. מדד תוצאה משני

    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.

    מסגרת זמן Median follow-up of 3.5 years

19. מדד תוצאה משני

    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.

    מסגרת זמן Median follow-up of 3.5 years

20. מדד תוצאה משני

    Fluoroscopic time for Staged PCI procedure

    Total time under fluoroscopy

    מסגרת זמן During PCI procedure

21. מדד תוצאה משני

    Contrast Utilization for Stages PCI Procedure

    מסגרת זמן During PCI procedure

תאריכים

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