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NCT Number: NCT06337838

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.

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Key information

Conditions

Chronic Kidney Diseases Acute Kidney Injury Bleeding Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hemorrhage Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Surgery Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

London Health Sciences Centre, London, Ontario, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Exclusion criteria

  • 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

  • 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.

Treatment and study plan

Desmopressin Injectable Solution

Drug

Intravenous desmopressin, 20 mcg, single dose administration.

Other names: DDAVP

Tranexamic Acid Injectable Product

Drug

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.

Other names: Cyklokapron

Placebo

Other

Intravenous 0.9% saline solution

Primary outcomes

  1. Rate of recruitment

    Time frame: Through study completion, an average of 1.5 years

    A rate of 0.25 patients per study site per week

  2. Receipt of the allocated study drug within 1 hour before start of surgery for the tranexamic acid factorial

    Time frame: 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

  3. Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial

    Time frame: 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

  4. Completion of 30-day follow-up

    Time frame: 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

Secondary outcomes

  1. Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)

    Time frame: 30 days after randomization

    Number of patients who experience BIMS

  2. Bleeding Score

    Time frame: 30 days after randomization

    10-category ordinal score. Minimum scores mean a better outcome. 0 denotes no bleeding or bleeding in which the nadir hemoglobin is ≥70 g/L, no red blood transfusion was given, no reoperation for reasons of bleeding occurred, and there was no death imminently or directly caused by bleeding.

    • denotes bleeding and post-operative hemoglobin <70 g/L or 1 unit of blood (red blood cells or whole blood) transfused.
    • denotes bleeding and 2 units transfused.
    • denotes bleeding and 3 units transfused.
    • denotes bleeding and 4 units transfused
    • denotes bleeding and 5 units transfused.
    • denotes bleeding and 6 units transfused.
    • denotes bleeding and 7 units transfused.
    • denotes bleeding and 8 or more units of blood transfused.
    • denotes reoperation for reasons of bleeding.
    • denotes death imminently or directly caused by bleeding.

  3. Reoperation for reasons of bleeding

    Time frame: 30 days after randomization

    Number of patients who return to the operating room for surgical management of suspected documented bleeding

  4. Blood (red blood cells or whole blood) transfused

    Time frame: 30 days after randomization

    Number of units of blood transfused.

  5. Blood (red blood cells or whole blood) transfused

    Time frame: Up to and including postoperative day 3 after surgery

    Number of units of blood transfused.

  6. Any blood transfusion (red blood cells or whole blood)

    Time frame: 30 days after randomization

    Number of units of blood transfused.

  7. Any blood transfusion (red blood cells or whole blood)

    Time frame: Up to and including postoperative day 3

    Number of units of blood transfused.

  8. Lowest measured hemoglobin concentration

    Time frame: 30 days after randomization

    The mean absolute difference for continuous outcomes using linear regression with treatment allocation

  9. Most recent hemoglobin concentration

    Time frame: 30 days after randomization

    The mean absolute difference for continuous outcomes using linear regression with treatment allocation

  10. Death

    Time frame: 30 days after randomization

    Number of patients who die of any cause

  11. Major arterial and venous thrombosis

    Time frame: 30 days after randomization

    (i.e., composite of myocardial injury after noncardiac surgery [MINS], stroke, peripheral arterial thrombosis, dialysis vascular access thrombosis requiring anticoagulation or intervention, and symptomatic venous thromboembolism)

  12. Myocardial Injury after Noncardiac Surgery (MINS)

    Time frame: 30 days after randomization

    Number of patients who experience MINS

  13. Myocardial Injury after Noncardiac Surgery (MINS) that meets criteria for myocardial infarction

    Time frame: 30 days after randomization

    Number of patients who experience MINS that meets criteria for myocardial infarction (based on the Fourth Universal Definition of myocardial infarction)

  14. MINS that is an isolated ischemic troponin elevation

    Time frame: 30 days after randomization

    Number of patients who experience MINS that is an isolated ischemic troponin elevation

  15. Stroke

    Time frame: 30 days after randomization

    Number of patients experiencing a stroke

  16. Non-hemorrhagic stroke

    Time frame: 30 days after randomization

    Number of patients who experience a non-hemorrhagic stroke

  17. Hemorrhagic stroke

    Time frame: 30 days after randomization

    Number of patients who experience a hemorrhagic stroke

  18. Peripheral arterial thrombosis

    Time frame: 30 days after randomization

    Number of patients who experience a peripheral arterial thrombosis

  19. Thrombosis of arteriovenous fistula or graft

    Time frame: 30 days after randomization

    Number of patients who have thrombosis of arteriovenous fistula or graft

  20. Symptomatic proximal venous thromboembolism

    Time frame: 30 days after randomization

    Number of patients who experience symptomatic proximal venous thromboembolism

  21. Symptomatic pulmonary embolism

    Time frame: 30 days after randomization

    Number of patients who experience a symptomatic pulmonary embolism

  22. Symptomatic proximal leg or arm deep venous thrombosis (DVT)

    Time frame: 30 days after randomization

    Number of patients who experience a symptomatic proximal leg or arm DVT

  23. Non-fatal cardiac arrest

    Time frame: 30 days after randomization

    Number of patients who experience non-fatal cardiac arrest

  24. Coronary revascularization procedure

    Time frame: 30 days after randomization

    Number of patients who undergo coronary revascularization procedure

  25. Clinically important atrial fibrillation or flutter

    Time frame: 30 days after randomization

    Number of patients who experience clinically important atrial fibrillation or flutter

  26. Acute heart failure or clinically important volume overload

    Time frame: 30 days after randomization

    Number of patients who experience acute heart failure or clinically important volume overload.

  27. Acute kidney injury (for patients not receiving dialysis before surgery)

    Time frame: 30 days after randomization

    Number of patients who experience an acute kidney injury

  28. New start of dialysis

    Time frame: 30 days after randomization

    Number of patients who require new start of dialysis

  29. Seizure

    Time frame: 30 days after randomization

    Number of patients who experience a seizure

  30. Clinically significant intraoperative hypotension

    Time frame: 30 days after randomization

    Number of patients who experience clinically significant intraoperative hypotension

  31. Clinically significant postoperative hypotension

    Time frame: Up to and including the end of postoperative day 1

    Number of patients who experience clinically significant postoperative hypotension

  32. Sepsis

    Time frame: 30 days after randomization

    Number of patients who experience sepsis

  33. Duration of surgery

    Time frame: 30 days after randomization

    The time from skin incision to closure, in minutes.

  34. Receipt of platelets

    Time frame: 30 days after randomization

    Any transfusion of this blood product

  35. Receipt of fibrinogen

    Time frame: 30 days after randomization

    Any transfusion of this blood product

  36. Receipt of fresh frozen plasma

    Time frame: 30 days after randomization

    Any transfusion of this blood product

  37. Receipt of cryoprecipitate

    Time frame: 30 days after randomization

    Any transfusion of this blood product

  38. Receipt of recombinant Factor VIIa

    Time frame: 30 days after randomization

    Number of patients receiving recombinant factor VIIa

  39. Receipt of prothrombin complex concentrate

    Time frame: 30 days after randomization

    Number of patients who receive prothrombin complex concentrate

  40. Prescribed erythropoiesis stimulating agent

    Time frame: 30 days after randomization

    Number of patients receiving a weekly dose of erythropoiesis stimulating agent on prescription active at 30 days

  41. Severe hyponatremia

    Time frame: Up to and including the end of postoperative day 1

    Measured serum sodium concentration <125 meq/L

  42. Duration of hospital stay after surgery

    Time frame: Day of surgery and ending the day of discharge

    Cumulative number of nights spent in an acute care hospital

  43. Duration of critical care stay after surgery

    Time frame: Day of surgery and ending the day of discharge

    Cumulative number of nights spent in an intensive care unit

  44. Delayed graft function after kidney transplantation

    Time frame: Within 7 days following kidney transplantation

    Receipt of dialysis

  45. Persistent dialysis dependence

    Time frame: 30 days after randomization

    Participant continues to receive dialysis after surgery.

  46. Incisional site pain severity

    Time frame: 30 days after randomization in the last 24 hours

    Rating of pain using the 10-point ordinal scale where 0 corresponds to no pain and 10 corresponds to the worst pain imaginable.

Study contacts

Contact information is provided by the study sponsor or research team.

Ingrid Copland

CONTACT

[email protected]

905-296-5754

Sponsors and collaborators

Lead sponsor

Hamilton Health Sciences Corporation

Other

Collaborators

  • Population Health Research Institute

Registry information

Acronym: BRACKETS

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Mar 29, 2024
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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