Reducing surgical bleeding in adults with advanced or acute kidney disease

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

This trial will test whether giving tranexamic acid or desmopressin before noncardiac surgery reduces bleeding in adults with advanced chronic kidney disease or recent acute kidney injury, including those on dialysis.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hamilton Health Sciences Corporation (Academic / other)
• Locations: 3 sites (London, Ontario and 2 other locations)
• Trial ID: NCT06337838 on ClinicalTrials.gov

What this trial studies

The BRACKETS pilot is a multicentre, randomized, placebo-controlled partial factorial trial testing prophylactic preoperative tranexamic acid (TXA) and desmopressin versus placebo in adults with severe chronic kidney disease or recent acute kidney injury undergoing noncardiac surgery. Participants are randomized to receive TXA or placebo and, in a partial factorial design, may also be randomized to desmopressin or its placebo; interventions are administered perioperatively with blinded outcome assessment. The pilot will test feasibility, provide preliminary efficacy and safety data, and collect pharmacokinetic information to inform dose selection in patients with impaired renal function. Findings will be used to design a larger international trial to determine whether these inexpensive, generic drugs can safely reduce perioperative bleeding in this high-risk group.

Who should consider this trial

Good fit: Adults (≥18 years) with estimated GFR <25 ml/min/1.73 m2 or receiving dialysis who are scheduled for noncardiac surgery requiring at least an overnight hospital stay and can provide informed consent are ideal candidates.

Not a fit: Patients undergoing cardiac or intracranial neurosurgery, those having dialysis access procedures, people already planned to receive prophylactic systemic antifibrinolytics, or those with known hypersensitivity to TXA are excluded and would not be expected to benefit from enrollment.

Why it matters

Potential benefit: If successful, these treatments could reduce perioperative bleeding, lower transfusion requirements, and decrease postoperative complications in people with severe kidney disease.

How similar studies have performed: Prior large trials in general surgical populations have shown benefit from TXA, but patients with advanced kidney disease were largely excluded and desmopressin has not been adequately tested in randomized trials for this indication, so the approach is partly supported by prior data but remains novel for this population.

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 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;
2. Planned noncardiac surgery (elective, urgent, or emergency 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 surgery for creation or revision of arteriovenous fistula or graft for dialysis access;
4. Planned use of prophylactic systemic TXA or ϵ-aminocaproic acid;
5. Hypersensitivity or known allergy to TXA;
6. History of seizure disorder;
7. Recent (within 90 days) stroke, myocardial infarction, acute arterial thrombosis, deep venous thrombosis, pulmonary embolism, or thrombosis of an arteriovenous fistula or graft;
8. History of thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, or antiphospholipid antibody syndrome;
9. 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
10. 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), hemophilia, or platelet function disorder; or
5. Hypersensitivity or known allergy to desmopressin.

Where this trial is running

London, Ontario and 2 other locations

• London Health Sciences Centre — London, Ontario, Canada (Recruiting)
• Centre Hospitalier de L'Universite de Montreal (CHUM) — Montreal, Quebec, Canada (Active_not_recruiting)
• McGill University University Health Centre — Montreal, Quebec, Canada (Active_not_recruiting)

Study contacts

• Principal investigator: Pavel Roshanov, MC,MSc,FRCPC — Western University
• Study coordinator: Ingrid Copland

Conditions Chronic Kidney Diseases; Acute Kidney Injury; Bleeding; Surgery; Major Noncardiac Surgery; Tranexamic Acid; Desmopressin