Rationale and design of the TUXEDO-2 India study: Ultra-Thin strUt Supraflex Cruz versus XiencE in a Diabetic pOpulation with multi-vessel disease-2.

BACKGROUND: The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS: The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS: In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS: The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Outcomes of cytoreductive surgery and HIPEC for pseudomyxoma peritonei of appendiceal origin from two Indian centers: A preliminary five-year experience.

PURPOSE: To evaluate the short-term outcomes of patients of pseudomyxoma peritonei (PMP) of appendiceal origin treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at two tertiary Indian centers. METHODS: Data was prospectively collected from January 2011 to January 2016. Palliative procedures were excluded. HIPEC was performed by the coliseum technique using either a mitomycin or oxaliplatin-based regimen. RESULTS: 77 procedures were performed on 71 patients. The average time interval between diagnosis and CRS was 15.3 months. Of the tumors, 22.1% were high grade, 77.9% low grade and 24.6% intermediate grade. The median peritoneal carcinomatosis index (PCI) was 26 (<25 in 70.1% and >30 in 38.9%). Completeness of cytoreduction score (CCS)-1 was achieved in 75.3% (CC-0 in 42.9%). The mean number of bowel anastomoses was 1.1 and the mean number of organs resected per patient was 3.3. Of the 77 patients, 71% had resection of 3 or more organs and 50.6% had resection of 4 or more organs. Grade 3-4 complications occurred in 42.9% of the patients and the perioperative mortality was 5.2%. The projected 5-year overall survival (OS) was 62.3% and the 3-year disease-free survival (DFS) was 71% at a median follow up of 13 months. CONCLUSION: CRS and HIPEC can be used to treat PMP with an acceptable morbidity and mortality in Indian patients. Lack of early referrals leads to a large portion of patients presenting with extensive disease and an inferior survival which should improve with increasing awareness about the procedure and its results.