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

NCT06337838 | Recruiting Phase 3 DMC

• 1 other identifier: 2024.BRACKETS-Pilot
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Chronic Kidney Diseases; Acute Kidney Injury; Bleeding; Surgery

Keywords

Major Noncardiac Surgery; Tranexamic Acid; Desmopressin

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (46)

• Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)

  30 days after randomization

• Bleeding Score

  30 days after randomization

• Reoperation for reasons of bleeding

  30 days after randomization

• Blood (red blood cells or whole blood) transfused

  30 days after randomization

• Blood (red blood cells or whole blood) transfused

  Up to and including postoperative day 3 after surgery

Study Arms (4)

Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin.

EXPERIMENTAL

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; Drug: Tranexamic Acid Injectable Product

Prophylactic intravenous tranexamic acid and placebo.

EXPERIMENTAL

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; Other: Placebo

Prophylactic intravenous desmopressin and placebo.

EXPERIMENTAL

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; Other: Placebo

Placebo and placebo.

PLACEBO COMPARATOR

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

Interventions

Desmopressin Injectable Solution DRUG

Intravenous desmopressin, 20 mcg, single dose administration.

Also known as: DDAVP

Prophylactic intravenous desmopressin and placebo.; Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin.

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.

Also known as: Cyklokapron

Prophylactic intravenous tranexamic acid and placebo.; Prophylactic intravenous tranexamic acid and prophylactic intravenous desmopressin.

Placebo OTHER

Intravenous 0.9% saline solution

Placebo and placebo.; Prophylactic intravenous desmopressin and placebo.; Prophylactic intravenous tranexamic acid and placebo.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of either:
• 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.

You may not qualify if:

• 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
• \. Included in the TXA factorial.
• The hospital does not have access to desmopressin;
• Planned use of prophylactic desmopressin;
• Most recent serum sodium concentration \< 130 mEq/L;

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• Population Health Research Institute: collaborator

Study Sites (3)

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

Centre Hospitalier de L'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

ACTIVE NOT RECRUITING

McGill University University Health Centre

Montreal, Quebec, H3H 2R9, Canada

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Acute Kidney Injury; Hemorrhage

Interventions

Deamino Arginine Vasopressin; Tranexamic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Pavel Roshanov, MC,MSc,FRCPC

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ingrid Copland

CONTACT

905-296-5754; brackets@phri.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drugs will be sourced locally and will be prepared by appropriately qualified center personnel who are independent of the study team to ensure blinding is maintained.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2x2 partial factorial design where patients are first randomized to receive prophylactic intravenous TXA versus placebo, and (when the study drug is available) to be randomized to receive prophylactic intravenous desmopressin versus placebo before noncardiac surgery.

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: March 29, 2024
• Study Start: June 9, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)