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

Phase 3RecruitingNCT06337838

Hamilton Health Sciences Corporation100 enrolled

Overview

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 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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

100

Conditions

Chronic Kidney Diseases Acute Kidney Injury Bleeding Surgery

Interventions

Desmopressin Injectable SolutionDRUG

Intravenous desmopressin, 20 mcg, single dose administration.

Tranexamic Acid Injectable ProductDRUG

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.

PlaceboOTHER

Intravenous 0.9% saline solution

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (2)

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

McGill University University Health Centre

Montreal, Quebec, Canada

ACTIVE_NOT_RECRUITING

Outcomes

Primary Outcomes

Rate of recruitment

A rate of 0.25 patients per study site per week

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 30 days after randomization

Secondary Outcomes

Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)

Number of patients who experience BIMS

Time frame: 30 days after randomization

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. 1. denotes bleeding and post-operative hemoglobin \<70 g/L or 1 unit of blood (red blood cells or whole blood) transfused. 2. denotes bleeding and 2 units transfused. 3. denotes bleeding and 3 units transfused. 4. denotes bleeding and 4 units transfused 5. denotes bleeding and 5 units transfused. 6. denotes bleeding and 6 units transfused. 7. denotes bleeding and 7 units transfused. 8. denotes bleeding and 8 or more units of blood transfused. 9. denotes reoperation for reasons of bleeding. 10. denotes death imminently or directly caused by bleeding.

Central Contacts

Ingrid Copland

CONTACT

905-296-5754 brackets@phri.ca

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: 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

Time frame: 30 days after randomization

Blood (red blood cells or whole blood) transfused

Number of units of blood transfused.

Time frame: 30 days after randomization

Blood (red blood cells or whole blood) transfused

Number of units of blood transfused.

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

Any blood transfusion (red blood cells or whole blood)

Number of units of blood transfused.

Time frame: 30 days after randomization

Any blood transfusion (red blood cells or whole blood)

Number of units of blood transfused.

Time frame: Up to and including postoperative day 3

Lowest measured hemoglobin concentration

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

Time frame: 30 days after randomization

Most recent hemoglobin concentration

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

Time frame: 30 days after randomization

Death

Number of patients who die of any cause

Time frame: 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)

Time frame: 30 days after randomization

Myocardial Injury after Noncardiac Surgery (MINS)

Number of patients who experience MINS

Time frame: 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)

Time frame: 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

Time frame: 30 days after randomization

Stroke

Number of patients experiencing a stroke

Time frame: 30 days after randomization

Non-hemorrhagic stroke

Number of patients who experience a non-hemorrhagic stroke

Time frame: 30 days after randomization

Hemorrhagic stroke

Number of patients who experience a hemorrhagic stroke

Time frame: 30 days after randomization

Peripheral arterial thrombosis

Number of patients who experience a peripheral arterial thrombosis

Time frame: 30 days after randomization

Thrombosis of arteriovenous fistula or graft

Number of patients who have thrombosis of arteriovenous fistula or graft

Time frame: 30 days after randomization

Symptomatic proximal venous thromboembolism

Number of patients who experience symptomatic proximal venous thromboembolism

Time frame: 30 days after randomization

Symptomatic pulmonary embolism

Number of patients who experience a symptomatic pulmonary embolism

Time frame: 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

Time frame: 30 days after randomization

Non-fatal cardiac arrest

Number of patients who experience non-fatal cardiac arrest

Time frame: 30 days after randomization

Coronary revascularization procedure

Number of patients who undergo coronary revascularization procedure

Time frame: 30 days after randomization

Clinically important atrial fibrillation or flutter

Number of patients who experience clinically important atrial fibrillation or flutter

Time frame: 30 days after randomization

Acute heart failure or clinically important volume overload

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

Time frame: 30 days after randomization

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

Number of patients who experience an acute kidney injury

Time frame: 30 days after randomization

New start of dialysis

Number of patients who require new start of dialysis

Time frame: 30 days after randomization

Seizure

Number of patients who experience a seizure

Time frame: 30 days after randomization

Clinically significant intraoperative hypotension

Number of patients who experience clinically significant intraoperative hypotension

Time frame: 30 days after randomization

Clinically significant postoperative hypotension

Number of patients who experience clinically significant postoperative hypotension

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

Sepsis

Number of patients who experience sepsis

Time frame: 30 days after randomization

Duration of surgery

The time from skin incision to closure, in minutes.

Time frame: 30 days after randomization

Receipt of platelets

Any transfusion of this blood product

Time frame: 30 days after randomization

Receipt of fibrinogen

Any transfusion of this blood product

Time frame: 30 days after randomization

Receipt of fresh frozen plasma

Any transfusion of this blood product

Time frame: 30 days after randomization

Receipt of cryoprecipitate

Any transfusion of this blood product

Time frame: 30 days after randomization

Receipt of recombinant Factor VIIa

Number of patients receiving recombinant factor VIIa

Time frame: 30 days after randomization

Receipt of prothrombin complex concentrate

Number of patients who receive prothrombin complex concentrate

Time frame: 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

Time frame: 30 days after randomization

Severe hyponatremia

Measured serum sodium concentration \<125 meq/L

Time frame: 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

Time frame: 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

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

Delayed graft function after kidney transplantation

Receipt of dialysis

Time frame: Within 7 days following kidney transplantation

Persistent dialysis dependence

Participant continues to receive dialysis after surgery.

Time frame: 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.

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