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

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.

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 severe 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.

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

1. One of either:

   1.1. eGFR \<25 ml/min/1.73m2 estimated using 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 hemodialysis or peritoneal dialysis in the preceding 7 days and expected to require dialysis after surgery;
2. Planned noncardiac surgery;
3. Expected to require at least an overnight hospital admission after surgery;
4. Age ≥18 years; and
5. Informed consent is obtained to participate in the BRACKETS-Pilot Trial.

Exclusion Criteria:

1. Undergoing cardiac surgery;
2. Undergoing intracranial neurosurgery;
3. Undergoing solid organ transplantation surgery (e.g., kidney, liver, pancreas, heart, lung, small bowel);
4. Undergoing surgery for creation or revision of arteriovenous fistula or graft for dialysis access;
5. Planned use of prophylactic systemic TXA or ϵ-aminocaproic acid;
6. Hypersensitivity or known allergy to TXA;
7. History of seizure disorder;
8. Recent (within 90 days) stroke, myocardial infarction, acute arterial thrombosis, venous thromboembolism, or dialysis access thrombosis of an arteriovenous fistula or graft;
9. History of thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, or antiphospholipid antibody syndrome;
10. Women of childbearing potential who are not taking effective contraception, pregnant, or breastfeeding; or
11. 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:

1. The hospital does not have access to desmopressin;
2. Planned use of prophylactic desmopressin;
3. Most recent serum sodium concentration \< 130 mEq/L;
4. Known or suspected von Willebrand disease (any kind), or platelet function disorder; or
5. Hypersensitivity or known allergy to desmopressin.