Bleeding Reduction in Acute and Chronic Kidney Patients Having Surgery (BRACKETS) Pilot Trial

Официальное название

Bleeding Reduction in Acute and Chronic KidnEy patienTs Having Surgery (BRACKETS) Pilot Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Desmopressin Injectable Solution
  Intravenous desmopressin, 20 mcg, single dose administration.
• Препарат Tranexamic Acid Injectable Product
  Intravenous tranexamic acid, 1000 mg single dose administration for patients with eGFR\<25 not yet receiving dialysis OR 500 mg single dose administration for patients receiving dialysis.
• Другое Placebo
  Intravenous 0.9% saline solution

Первичные конечные точки

• Rate of recruitment [Срок оценки: Through study completion, an average of 1.5 years]
• Receipt of the allocated study drug within 1 hour before start of surgery for the tranexamic acid factorial [Срок оценки: Day of surgery]
• Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial [Срок оценки: Day of surgery]
• Completion of 30-day follow-up [Срок оценки: 30 days after randomization]

Вторичные конечные точки (12)

• Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS) [Срок оценки: 30 days after randomization]
• Bleeding Score [Срок оценки: 30 days after randomization]
• Reoperation for reasons of bleeding [Срок оценки: 30 days after randomization]
• Blood (red blood cells or whole blood) transfused [Срок оценки: 30 days after randomization]
• Blood (red blood cells or whole blood) transfused [Срок оценки: Up to and including postoperative day 3 after surgery]
• Any blood transfusion (red blood cells or whole blood) [Срок оценки: 30 days after randomization]
• Any blood transfusion (red blood cells or whole blood) [Срок оценки: Up to and including postoperative day 3]
• Lowest measured hemoglobin concentration [Срок оценки: 30 days after randomization]
• Most recent hemoglobin concentration [Срок оценки: 30 days after randomization]
• Death [Срок оценки: 30 days after randomization]
• Major arterial and venous thrombosis [Срок оценки: 30 days after randomization]
• Myocardial Injury after Noncardiac Surgery (MINS) [Срок оценки: 30 days after randomization]

Критерии участия

Eligibility criteria specific to the tranexamic acid (TXA) factorial component of trial Inclusion Criteria:

• One of either:

1.1. 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 1.2. 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.

Критерии исключения

• 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

Критерии включения

1\. Included in the TXA factorial.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 3 центра

• London Health Sciences Centre — London
• Centre Hospitalier de L'Universite de Montreal (CHUM) — Montreal
• McGill University University Health Centre — Montreal

Идентификаторы

NCT: NCT06337838 · 2024.BRACKETS-Pilot

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗