Marcucci Maura, Duceppe Emmanuelle, Le Manach Yannick, Kearon Clive, Eikelboom John W, Pohl Kayla, Vincent Jessica, Darvish-Kazem Saeed, Srinathan Sadeesh K, Neary John D D, Parlow Joel L, Kurz Andrea, Gross Peter L, Mrkobrada Marko, Balasubramanian Kumar, Sessler Daniel I, Devereaux P J
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON Canada.
Department of Medicine, McMaster University, Hamilton, ON Canada.
Pilot Feasibility Stud. 2020 Jul 21;6:104. doi: 10.1186/s40814-020-00643-9. eCollection 2020.
Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin.
Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored.
After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients.
Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance.
ClinicalTrials.govNCT02546648.
手术出血与术后心血管并发症相关。氨甲环酸（TXA）在非心脏手术中的有效性和安全性仍不确定。他汀类药物可能预防围手术期心血管并发症。我们进行了一项初步试验，以评估TXA和瑞舒伐他汀围手术期试验的可行性。
采用析因设计，我们将接受非心脏手术且有心血管风险的患者随机分为静脉注射TXA组（手术开始和结束时各1g）或安慰剂组，以及口服瑞舒伐他汀组（术前40mg，术后30天每天20mg）或安慰剂组。可行性指标包括招募率、随访情况和干预措施的依从性。次要指标为临床结局。
3个月后，由于难以招募未使用过他汀类药物的患者，我们将设计改为部分析因设计。在6个月内，100例患者被随机分配到TXA试验组（49例TXA，51例安慰剂），34例患者被随机分配到瑞舒伐他汀试验组（18例瑞舒伐他汀，16例安慰剂）。92%（95%CI 80 - 98）的TXA组和86%（95%CI 74 - 94）的TXA-安慰剂组患者接受了2次研究剂量。33%（95%CI 13 - 59）的瑞舒伐他汀组患者和37%（95%CI 15 - 65）的瑞舒伐他汀-安慰剂组患者停用了研究药物。1例TXA组和6例TXA-安慰剂组患者在30天时发生了主要心血管并发症，1例瑞舒伐他汀组患者和0例瑞舒伐他汀-安慰剂组患者发生了主要心血管并发症。
我们的初步研究支持在非心脏手术中进行TXA围手术期试验的可行性。由于目标人群中他汀类药物的高使用率以及对依从性的担忧，瑞舒伐他汀围手术期试验的可行性尚不确定。
ClinicalTrials.govNCT02546648
