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

Surgery Clinical Trial

— BRACKETS  

Official title:

Bleeding Reduction in Acute and Chronic KidnEy patienTs Having Surgery (BRACKETS) Pilot Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06337838
• Other study ID #: 2024.BRACKETS-Pilot
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: March 2026

Study information

• Verified date: March 2024
• Source: Population Health Research Institute
• Contact: Ingrid Copland
• Phone: 905-296-5754
• Email: brackets[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 severe 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 hemodialysis or peritoneal dialysis in the preceding 7 days and expected to require dialysis after surgery;

2. Planned noncardiac 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 solid organ transplantation surgery (e.g., kidney, liver, pancreas, heart, lung, small bowel);

4. Undergoing surgery for creation or revision of arteriovenous fistula or graft for dialysis access;

5. Planned use of prophylactic systemic TXA or ?-aminocaproic acid;

6. Hypersensitivity or known allergy to TXA;

7. History of seizure disorder;

8. Recent (within 90 days) stroke, myocardial infarction, acute arterial thrombosis, venous thromboembolism, or dialysis access thrombosis of an arteriovenous fistula or graft;

9. History of thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, or antiphospholipid antibody syndrome;

10. Women of childbearing potential who are not taking effective contraception, pregnant, or breastfeeding; or

11. 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), or platelet function disorder; or

5. Hypersensitivity or known allergy to desmopressin.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Bleeding
• Chronic Kidney Diseases
• Hemorrhage
• Kidney Diseases
• Renal Insufficiency, Chronic
• Surgery

Intervention

Drug:
• Desmopressin Injectable Solution
Intravenous desmopressin, 20 mcg, single dose administration.
• 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:
• Placebo
Intravenous 0.9% saline solution

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of recruitment	A rate of 0.25 patients per study site per week	Through study completion, an average of 1.5 years
Primary	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
Primary	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
Primary	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	Bleeding Independently Associated with Mortality after noncardiac Surgery (BIMS)	Number of patients who experience BIMS	30 days after randomization
Secondary	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
Secondary	Blood (red blood cells or whole blood) transfused	Number of units of blood transfused.	30 days after randomization
Secondary	Blood (red blood cells or whole blood) transfused	Number of units of blood transfused.	Up to and including postoperative day 3 after surgery
Secondary	Any blood transfusion (red blood cells or whole blood)	Number of units of blood transfused.	30 days after randomization
Secondary	Any blood transfusion (red blood cells or whole blood)	Number of units of blood transfused.	Up to and including postoperative day 3
Secondary	Lowest measured hemoglobin concentration	The mean absolute difference for continuous outcomes using linear regression with treatment allocation	30 days after randomization
Secondary	Most recent hemoglobin concentration	The mean absolute difference for continuous outcomes using linear regression with treatment allocation	30 days after randomization
Secondary	Death	Number of patients who die of any cause	30 days after randomization
Secondary	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
Secondary	Myocardial Injury after Noncardiac Surgery (MINS)	Number of patients who experience MINS	30 days after randomization
Secondary	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
Secondary	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
Secondary	Stroke	Number of patients experiencing a stroke	30 days after randomization
Secondary	Non-hemorrhagic stroke	Number of patients who experience a non-hemorrhagic stroke	30 days after randomization
Secondary	Hemorrhagic stroke	Number of patients who experience a hemorrhagic stroke	30 days after randomization
Secondary	Peripheral arterial thrombosis	Number of patients who experience a peripheral arterial thrombosis	30 days after randomization
Secondary	Thrombosis of arteriovenous fistula or graft	Number of patients who have thrombosis of arteriovenous fistula or graft	30 days after randomization
Secondary	Symptomatic proximal venous thromboembolism	Number of patients who experience symptomatic proximal venous thromboembolism	30 days after randomization
Secondary	Symptomatic pulmonary embolism	Number of patients who experience a symptomatic pulmonary embolism	30 days after randomization
Secondary	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
Secondary	Non-fatal cardiac arrest	Number of patients who experience non-fatal cardiac arrest	30 days after randomization
Secondary	Coronary revascularization procedure	Number of patients who undergo coronary revascularization procedure	30 days after randomization
Secondary	Clinically important atrial fibrillation or flutter	Number of patients who experience clinically important atrial fibrillation or flutter	30 days after randomization
Secondary	Acute heart failure	Number of patients who experience acute heart failure	30 days after randomization
Secondary	Acute kidney injury (for patients not receiving dialysis before surgery)	Number of patients who experience an acute kidney injury	30 days after randomization
Secondary	New start of dialysis	Number of patients who require new start of dialysis	30 days after randomization
Secondary	Seizure	Number of patients who experience a seizure	30 days after randomization
Secondary	Clinically significant intraoperative hypotension	Number of patients who experience clinically significant intraoperative hypotension	30 days after randomization
Secondary	Clinically significant postoperative hypotension	Number of patients who experience clinically significant postoperative hypotension	Up to and including the end of postoperative day 1
Secondary	Sepsis	Number of patients who experience sepsis	30 days after randomization
Secondary	Duration of surgery	The time from skin incision to closure, in minutes.	30 days after randomization
Secondary	Receipt of platelets	Any transfusion of this blood product	30 days after randomization
Secondary	Receipt of fibrinogen	Any transfusion of this blood product	30 days after randomization
Secondary	Receipt of fresh frozen plasma	Any transfusion of this blood product	30 days after randomization
Secondary	Receipt of cryoprecipitate	Any transfusion of this blood product	30 days after randomization
Secondary	Receipt of recombinant Factor VIIa	Number of patients receiving recombinant factor VIIa	30 days after randomization
Secondary	Receipt of prothrombin complex concentrate	Number of patients who receive prothrombin complex concentrate	30 days after randomization
Secondary	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
Secondary	Severe hyponatremia	Measured serum sodium concentration <125 meq/L	Up to and including the end of postoperative day 1
Secondary	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
Secondary	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