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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Bleeding; Surgery; Acute Kidney Injury
• Intervention / Treatment: Drug: Desmopressin Injectable Solution; Drug: Tranexamic Acid Injectable Product; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ingrid Copland; Phone Number: 905-296-5754; Email: brackets@phri.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre
      • Contact: Cadence Baker; Phone Number: 34769 519-685-8500; Email: cadence.baker@lhsc.on.ca
      • Principal Investigator: Pavel Roshanov, MD
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Active, not recruiting
      • Centre hospitalier de l'Université de Montréal (CHUM)
    • Montreal, Quebec, Canada, H3H 2R9
      • Recruiting
      • McGill University University Health Centre
      • Principal Investigator: Shaifali Sandal, MD
      • Contact: Lin Jawhar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Desmopressin Injectable Solution; Intravenous desmopressin, 20 mcg, single dose administration.; Other Names: DDAVP; Drug: 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.; Other Names: Cyklokapron
Experimental: 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.	Drug: 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.; Other Names: Cyklokapron; Other: Placebo; Intravenous 0.9% saline solution
Experimental: 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.	Drug: Desmopressin Injectable Solution; Intravenous desmopressin, 20 mcg, single dose administration.; Other Names: DDAVP; Other: Placebo; Intravenous 0.9% saline solution
Placebo Comparator: 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.	Other: Placebo; Intravenous 0.9% saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of recruitment	A rate of 0.25 patients per study site per week	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	Account of whether the patient began to receive study drug for the TXA factorial within an hour before skin incision. Target ≥80% of participants	Day of surgery
Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial	Account of whether the patient began to receive study drug for the desmopressin factorial within an hour before skin incision. Target ≥80% of participants	Day of surgery
Completion of 30-day follow-up	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	30 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	30 days after randomization
Hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	30 days after randomization
Symptomatic pulmonary embolism	Number of patients who experience a symptomatic pulmonary embolism	30 days after randomization
Non-fatal cardiac arrest	Number of patients who experience non-fatal cardiac arrest	30 days after randomization
Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)	Number of patients who experience BIMS	30 days after randomization
Reoperation for reasons of bleeding	Number of patients who return to the operating room for surgical management of suspected documented bleeding	30 days after randomization
Blood (red blood cells or whole blood) transfused	Number of units of blood transfused.	30 days after randomization
Blood (red blood cells or whole blood) transfused	Number of units of blood transfused.	Up to and including postoperative day 3 after surgery
Any blood transfusion (red blood cells or whole blood)	Number of units of blood transfused.	30 days after randomization
Any blood transfusion (red blood cells or whole blood)	Number of units of blood transfused.	Up to and including postoperative day 3
Lowest measured hemoglobin concentration	The mean absolute difference for continuous outcomes using linear regression with treatment allocation	30 days after randomization
Most recent hemoglobin concentration	The mean absolute difference for continuous outcomes using linear regression with treatment allocation	30 days after randomization
Death	Number of patients who die of any cause	30 days after randomization
Major arterial and venous thrombosis	(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)	30 days after randomization
Myocardial Injury after Noncardiac Surgery (MINS)	Number of patients who experience MINS	30 days after randomization
Myocardial Injury after Noncardiac Surgery (MINS) that meets criteria for myocardial infarction	Number of patients who experience MINS that meets criteria for myocardial infarction (based on the Fourth Universal Definition of myocardial infarction)	30 days after randomization
MINS that is an isolated ischemic troponin elevation	Number of patients who experience MINS that is an isolated ischemic troponin elevation	30 days after randomization
Stroke	Number of patients experiencing a stroke	30 days after randomization
Peripheral arterial thrombosis	Number of patients who experience a peripheral arterial thrombosis	30 days after randomization
Thrombosis of arteriovenous fistula or graft	Number of patients who have thrombosis of arteriovenous fistula or graft	30 days after randomization
Symptomatic proximal venous thromboembolism	Number of patients who experience symptomatic proximal venous thromboembolism	30 days after randomization
Symptomatic proximal leg or arm deep venous thrombosis (DVT)	Number of patients who experience a symptomatic proximal leg or arm DVT	30 days after randomization
Coronary revascularization procedure	Number of patients who undergo coronary revascularization procedure	30 days after randomization
Clinically important atrial fibrillation or flutter	Number of patients who experience clinically important atrial fibrillation or flutter	30 days after randomization
Acute kidney injury (for patients not receiving dialysis before surgery)	Number of patients who experience an acute kidney injury	30 days after randomization
New start of dialysis	Number of patients who require new start of dialysis	30 days after randomization
Seizure	Number of patients who experience a seizure	30 days after randomization
Clinically significant intraoperative hypotension	Number of patients who experience clinically significant intraoperative hypotension	30 days after randomization
Clinically significant postoperative hypotension	Number of patients who experience clinically significant postoperative hypotension	Up to and including the end of postoperative day 1
Sepsis	Number of patients who experience sepsis	30 days after randomization
Duration of surgery	The time from skin incision to closure, in minutes.	30 days after randomization
Receipt of platelets	Any transfusion of this blood product	30 days after randomization
Receipt of fibrinogen	Any transfusion of this blood product	30 days after randomization
Receipt of fresh frozen plasma	Any transfusion of this blood product	30 days after randomization
Receipt of cryoprecipitate	Any transfusion of this blood product	30 days after randomization
Receipt of recombinant Factor VIIa	Number of patients receiving recombinant factor VIIa	30 days after randomization
Receipt of prothrombin complex concentrate	Number of patients who receive prothrombin complex concentrate	30 days after randomization
Prescribed erythropoiesis stimulating agent	Number of patients receiving a weekly dose of erythropoiesis stimulating agent on prescription active at 30 days	30 days after randomization
Severe hyponatremia	Measured serum sodium concentration <125 meq/L	Up to and including the end of postoperative day 1
Duration of hospital stay after surgery	Cumulative number of nights spent in an acute care hospital	Day of surgery and ending the day of discharge
Duration of critical care stay after surgery	Cumulative number of nights spent in an intensive care unit	Day of surgery and ending the day of discharge
Acute heart failure or clinically important volume overload	Number of patients who experience acute heart failure or clinically important volume overload.	30 days after randomization
Delayed graft function after kidney transplantation	Receipt of dialysis	Within 7 days following kidney transplantation
Persistent dialysis dependence	Participant continues to receive dialysis after surgery.	30 days after randomization
Incisional site pain severity	Rating of pain using the 10-point ordinal scale where 0 corresponds to no pain and 10 corresponds to the worst pain imaginable.	30 days after randomization in the last 24 hours
Bleeding Score	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.	30 days after randomization

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Population Health Research Institute
• Investigators: Principal Investigator: Pavel Roshanov, MC,MSc,FRCPC, Western University

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Desmopressin; Tranexamic Acid; Major Noncardiac Surgery
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Acute Kidney Injury; Renal Insufficiency, Chronic; Hemorrhage; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Pituitary Hormones, Posterior; Pituitary Hormones; Arginine Vasopressin; Vasopressins; Tranexamic Acid; Deamino Arginine Vasopressin
• Other Study ID Numbers: 2024.BRACKETS-Pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No