Clinical trial NCT06337838: Bleeding Reduction in Acute and Chronic Kidney Patients Having Surgery (BRACKETS) Pilot Trial
Official title: Bleeding Reduction in Acute and Chronic KidnEy patienTs Having Surgery (BRACKETS) Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Kidney Diseases
Acute Kidney Injury
Bleeding
Surgery
Keywords: Major Noncardiac Surgery
Tranexamic Acid
Desmopressin
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
First posted: 2024-03-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Rate of recruitment
timeFrame: Through study completion, an average of 1.5 years
measure: Receipt of the allocated study drug within 1 hour before start of surgery for the tranexamic acid factorial
timeFrame: Day of surgery
measure: Receipt of the allocated study drug within 1 hour before start of surgery for the desmopressin factorial
timeFrame: Day of surgery
measure: Completion of 30-day follow-up
timeFrame: 30 days after randomization
Secondary outcomes:
measure: Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)
timeFrame: 30 days after randomization
measure: Bleeding Score
timeFrame: 30 days after randomization
measure: Reoperation for reasons of bleeding
timeFrame: 30 days after randomization
measure: Blood (red blood cells or whole blood) transfused
timeFrame: 30 days after randomization
measure: Blood (red blood cells or whole blood) transfused
timeFrame: Up to and including postoperative day 3 after surgery
measure: Any blood transfusion (red blood cells or whole blood)
timeFrame: 30 days after randomization
measure: Any blood transfusion (red blood cells or whole blood)
timeFrame: Up to and including postoperative day 3
measure: Lowest measured hemoglobin concentration
timeFrame: 30 days after randomization
measure: Most recent hemoglobin concentration
timeFrame: 30 days after randomization
measure: Death
timeFrame: 30 days after randomization
measure: Major arterial and venous thrombosis
timeFrame: 30 days after randomization
measure: Myocardial Injury after Noncardiac Surgery (MINS)
timeFrame: 30 days after randomization
measure: Myocardial Injury after Noncardiac Surgery (MINS) that meets criteria for myocardial infarction
timeFrame: 30 days after randomization
measure: MINS that is an isolated ischemic troponin elevation
timeFrame: 30 days after randomization
measure: Stroke
timeFrame: 30 days after randomization
measure: Non-hemorrhagic stroke
timeFrame: 30 days after randomization
measure: Hemorrhagic stroke
timeFrame: 30 days after randomization
measure: Peripheral arterial thrombosis
timeFrame: 30 days after randomization
measure: Thrombosis of arteriovenous fistula or graft
timeFrame: 30 days after randomization
measure: Symptomatic proximal venous thromboembolism
timeFrame: 30 days after randomization
measure: Symptomatic pulmonary embolism
timeFrame: 30 days after randomization
measure: Symptomatic proximal leg or arm deep venous thrombosis (DVT)
timeFrame: 30 days after randomization
measure: Non-fatal cardiac arrest
timeFrame: 30 days after randomization
measure: Coronary revascularization procedure
timeFrame: 30 days after randomization
measure: Clinically important atrial fibrillation or flutter
timeFrame: 30 days after randomization
measure: Acute heart failure or clinically important volume overload
timeFrame: 30 days after randomization
measure: Acute kidney injury (for patients not receiving dialysis before surgery)
timeFrame: 30 days after randomization
measure: New start of dialysis
timeFrame: 30 days after randomization
measure: Seizure
timeFrame: 30 days after randomization
measure: Clinically significant intraoperative hypotension
timeFrame: 30 days after randomization
measure: Clinically significant postoperative hypotension
timeFrame: Up to and including the end of postoperative day 1
measure: Sepsis
timeFrame: 30 days after randomization
measure: Duration of surgery
timeFrame: 30 days after randomization
measure: Receipt of platelets
timeFrame: 30 days after randomization
measure: Receipt of fibrinogen
timeFrame: 30 days after randomization
measure: Receipt of fresh frozen plasma
timeFrame: 30 days after randomization
measure: Receipt of cryoprecipitate
timeFrame: 30 days after randomization
measure: Receipt of recombinant Factor VIIa
timeFrame: 30 days after randomization
measure: Receipt of prothrombin complex concentrate
timeFrame: 30 days after randomization
measure: Prescribed erythropoiesis stimulating agent
timeFrame: 30 days after randomization
measure: Severe hyponatremia
timeFrame: Up to and including the end of postoperative day 1
measure: Duration of hospital stay after surgery
timeFrame: Day of surgery and ending the day of discharge
measure: Duration of critical care stay after surgery
timeFrame: Day of surgery and ending the day of discharge
measure: Delayed graft function after kidney transplantation
timeFrame: Within 7 days following kidney transplantation
measure: Persistent dialysis dependence
timeFrame: 30 days after randomization
measure: Incisional site pain severity
timeFrame: 30 days after randomization in the last 24 hours
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Western University
name: Pavel Roshanov, MC,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: