Bleeding Reduction in Acute and Chronic KidnEy patienTs Having Surgery (BRACKETS) Pilot Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 3
- 主要终点
- Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial
研究概览
简要总结
The BRACKETS pilot study is a multicentre, prospective, randomized controlled trial of prophylactic preoperative tranexamic acid (TXA) versus placebo and, using a partial factorial design, of prophylactic preoperative desmopressin versus placebo.
详细描述
Perioperative administration of TXA reduces bleeding risk in surgical patients. However, large clinical trials have excluded patients with advanced kidney disease, so the benefits remain uncertain in this population, and there is potential for harm. The benefit of desmopressin, which is purported to more directly address the defect of primary hemostasis believed important in severe kidney disease more directly than TXA, has not been examined in adequate randomized control trials (RCTs). Both medications are generic and have been available for many years. To convincingly test these medications in patients with severe kidney disease, large, global trials are required. This pilot-phase trial will 1) inform the feasibility and design of a large international trial to evaluate the efficacy and safety of TXA and desmopressin in patients with advanced kidney disease undergoing noncardiac surgery, 2) provide preliminary data regarding the efficacy and safety of TXA and desmopressin in people with advanced kidney disease having noncardiac surgery, and 3) provide pharmacokinetic data to inform dose selection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Study drugs will be sourced locally and will be prepared by appropriately qualified center personnel who are independent of the study team to ensure blinding is maintained.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligibility criteria specific to the tranexamic acid (TXA) factorial component of trial Inclusion Criteria:
- •One of either:
- •eGFR <25 ml/min/1.73m2 estimated using the CKD-Epi 2009 or 2021creatinine-based equation from the most recent serum creatinine measurement done in the previous 6 months; or 1.
- •Receipt of dialysis (including hemodialysis, peritoneal dialysis, hemofiltration, or hemodiafiltration) within the last 7 days;
- •Planned noncardiac surgery (elective, urgent, or emergency surgery);
- •Expected to require at least an overnight hospital admission after surgery;
- •Age ≥18 years; and
- •Informed consent is obtained to participate in the BRACKETS-Pilot Trial.
排除标准
- •Undergoing cardiac surgery;
- •Undergoing intracranial neurosurgery;
- •Undergoing surgery for creation or revision of arteriovenous fistula or graft for dialysis access;
- •Planned use of prophylactic systemic TXA or ϵ-aminocaproic acid;
- •Hypersensitivity or known allergy to TXA;
- •History of seizure disorder;
- •Recent (within 90 days) stroke, myocardial infarction, acute arterial thrombosis, deep venous thrombosis, pulmonary embolism, or thrombosis of an arteriovenous fistula or graft;
- •History of thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, or antiphospholipid antibody syndrome;
- •Women who are known to be pregnant, breastfeeding, or who meet both of the following criteria: i) are of childbearing potential and do not have a negative pregnancy test documented in the 7 days before surgery, AND ii) are not using effective contraception; or
- •Previously enrolled in the BRACKETS-Pilot Trial.
- •Eligibility criteria specific to the desmopressin factorial component of trial
- •Inclusion criteria:
- •1. Included in the TXA factorial.
- •Exclusion criteria:
- •The hospital does not have access to desmopressin;
- •Planned use of prophylactic desmopressin;
- •Most recent serum sodium concentration < 130 mEq/L;
- •Known or suspected von Willebrand disease (any kind), hemophilia, or platelet function disorder; or
- •Hypersensitivity or known allergy to desmopressin.
研究组 & 干预措施
Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin.
Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with estimated glomerular filtration rate (eGFR) <25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis.
Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin intervention group will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes.
干预措施: Desmopressin Injectable Solution (Drug)
Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin.
Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with estimated glomerular filtration rate (eGFR) <25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis.
Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin intervention group will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes.
干预措施: Tranexamic Acid Injectable Product (Drug)
Prophylactic intravenous desmopressin and placebo.
Within 20 minutes preceding anticipated skin incision, patients will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes. Patients will not receive prophylactic tranexamic acid.
Within 20 minutes preceding anticipated skin incision, patients allocated to the tranexamic acid control group will receive an intravenous infusion of 0.9% saline solution. This saline solution will be administered over a duration of 10 minutes in a volume equivalent to that received by patients in the tranexamic acid intervention group.
干预措施: Desmopressin Injectable Solution (Drug)
Prophylactic intravenous tranexamic acid and placebo.
Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with eGFR <25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis.
Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin control group will receive an intravenous infusion of 0.9% saline solution, administered over a duration of 30 minutes.
干预措施: Tranexamic Acid Injectable Product (Drug)
Prophylactic intravenous tranexamic acid and placebo.
Within 20 minutes preceding anticipated skin incision, patients will receive preoperative prophylactic intravenous tranexamic acid at a dose of 1000 mg infused over 10 minutes for patients with eGFR <25 ml/min/1.73m2 who do not receive dialysis before surgery and 500 mg infused over 10 minutes for patients who receive dialysis.
Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin control group will receive an intravenous infusion of 0.9% saline solution, administered over a duration of 30 minutes.
干预措施: Placebo (Other)
Placebo and placebo.
Within 20 minutes preceding anticipated skin incision, patients allocated to the tranexamic acid control group will receive an intravenous infusion of 0.9% saline solution. This saline solution will be administered over a duration of 10 minutes in a volume equivalent to that received by patients in the tranexamic acid intervention group.
Within 20 minutes preceding anticipated skin incision, patients allocated to the desmopressin control group will receive an intravenous infusion of 0.9% saline solution, administered over a duration of 30 minutes.
干预措施: Placebo (Other)
Prophylactic intravenous desmopressin and placebo.
Within 20 minutes preceding anticipated skin incision, patients will receive intravenous desmopressin at a dose of 20 mcg over 30 minutes. Patients will not receive prophylactic tranexamic acid.
Within 20 minutes preceding anticipated skin incision, patients allocated to the tranexamic acid control group will receive an intravenous infusion of 0.9% saline solution. This saline solution will be administered over a duration of 10 minutes in a volume equivalent to that received by patients in the tranexamic acid intervention group.
干预措施: Placebo (Other)
结局指标
主要结局
Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial
时间窗: Day of surgery
Account of whether the patient began to receive study drug for the desmopressin factorial within an hour before skin incision. Target ≥80% of participants
Completion of 30-day follow-up
时间窗: 30 days after randomization
Account of whether the patient or their next-of-kin could be contacted and completed the 30-day post-randomization assessment. Target ≥80% of participants
Rate of recruitment
时间窗: Through study completion, an average of 1.5 years
A rate of 0.25 patients per study site per week
Receipt of the allocated study drug within 1 hour before start of surgery for the tranexamic acid factorial
时间窗: Day of surgery
Account of whether the patient began to receive study drug for the TXA factorial within an hour before skin incision. Target ≥80% of participants
次要结局
- Hemorrhagic stroke(30 days after randomization)
- Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)(30 days after randomization)
- Bleeding Score(30 days after randomization)
- Reoperation for reasons of bleeding(30 days after randomization)
- Blood (red blood cells or whole blood) transfused(Up to and including postoperative day 3 after surgery)
- Any blood transfusion (red blood cells or whole blood)(Up to and including postoperative day 3)
- Lowest measured hemoglobin concentration(30 days after randomization)
- Most recent hemoglobin concentration(30 days after randomization)
- Death(30 days after randomization)
- Major arterial and venous thrombosis(30 days after randomization)
- Myocardial Injury after Noncardiac Surgery (MINS)(30 days after randomization)
- Myocardial Injury after Noncardiac Surgery (MINS) that meets criteria for myocardial infarction(30 days after randomization)
- MINS that is an isolated ischemic troponin elevation(30 days after randomization)
- Stroke(30 days after randomization)
- Non-hemorrhagic stroke(30 days after randomization)
- Peripheral arterial thrombosis(30 days after randomization)
- Thrombosis of arteriovenous fistula or graft(30 days after randomization)
- Symptomatic proximal venous thromboembolism(30 days after randomization)
- Symptomatic pulmonary embolism(30 days after randomization)
- Symptomatic proximal leg or arm deep venous thrombosis (DVT)(30 days after randomization)
- Non-fatal cardiac arrest(30 days after randomization)
- Coronary revascularization procedure(30 days after randomization)
- Clinically important atrial fibrillation or flutter(30 days after randomization)
- Acute heart failure or clinically important volume overload(30 days after randomization)
- Acute kidney injury (for patients not receiving dialysis before surgery)(30 days after randomization)
- New start of dialysis(30 days after randomization)
- Seizure(30 days after randomization)
- Clinically significant intraoperative hypotension(30 days after randomization)
- Clinically significant postoperative hypotension(Up to and including the end of postoperative day 1)
- Sepsis(30 days after randomization)
- Duration of surgery(30 days after randomization)
- Receipt of platelets(30 days after randomization)
- Receipt of fibrinogen(30 days after randomization)
- Receipt of fresh frozen plasma(30 days after randomization)
- Receipt of cryoprecipitate(30 days after randomization)
- Receipt of recombinant Factor VIIa(30 days after randomization)
- Receipt of prothrombin complex concentrate(30 days after randomization)
- Prescribed erythropoiesis stimulating agent(30 days after randomization)
- Severe hyponatremia(Up to and including the end of postoperative day 1)
- Duration of hospital stay after surgery(Day of surgery and ending the day of discharge)
- Duration of critical care stay after surgery(Day of surgery and ending the day of discharge)
- Delayed graft function after kidney transplantation(Within 7 days following kidney transplantation)
- Persistent dialysis dependence(30 days after randomization)
- Incisional site pain severity(30 days after randomization in the last 24 hours)
- Blood (red blood cells or whole blood) transfused(30 days after randomization)
- Any blood transfusion (red blood cells or whole blood)(30 days after randomization)