Tranexamic Acid During Cystectomy Trial (TACT)

NCT ID: NCT01869413

Last Updated: 2022-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2021-06-30

Brief Summary

A cystectomy is the removal of the bladder and adjacent organs in patients with bladder cancer. This often results in significant blood loss, and about 60% of patients will require a blood transfusion during or up to 30 days after surgery. Significant blood loss may result in cardiovascular morbidity, and the use of blood products are expensive and expose patients to risk.

Tranexamic acid reduces breakdown of hemostatic blood clots and it has therapeutic benefit when used in other surgical procedures to reduce blood loss and the need for transfusion. The current study will be the first to evaluate whether tranexamic acid is effective and safe to use during radical cystectomy. The results of the study will have an immediate impact on patient care.

Detailed Description

Removal of the bladder and adjacent organs in patients with bladder cancer (radical cystectomy) often results in significant blood loss, and approximately 60% of patients require peri-operative blood transfusion. Reducing blood loss and the frequency of transfusion offers several benefits, including donor blood conservation, health care cost reduction, and avoidance of blood product exposure. Tranexamic acid is an amino acid lysine derivative with strong antifibrinolytic clotting properties that can be administered systemically. This medication has been used in a variety of operative procedures, notably in high risk cardiac surgery, to decrease peri-operative blood loss, and it is associated with an acceptable risk of adverse events. Systemic anti-hemorrhagics are infrequently used during radical cystectomy, and to the investigators knowledge their effects have not been evaluated in a clinical trial.

Overall objective: To conduct a randomized controlled trial of systemic tranexamic acid compared to placebo in reducing the number of blood transfusions in patients undergoing radical cystectomy for bladder cancer.

Design: A multi-center, randomized, double-blinded, placebo controlled trial.

Study population: Consenting patients 18 years of age and older undergoing a radical cystectomy for bladder cancer, excluding those who: are unwilling to receive blood products due to personal reasons, are pregnant, have active angina, have a known allergy to tranexamic acid, or have a known personal history of deep venous thrombosis, atrial fibrillation, coronary stent, sub-arachnoid hemorrhage, pulmonary embolism, thrombotic stroke and / or acquired disturbance of colour vision. The study will recruit 354 patients from Dalhousie University, McGill University, Université de Montreal, Université Laval, University of Ottawa, University of Western Ontario and University of Alberta.

Intervention:

Tranexamic Acid arm: Tranexamic acid will be administered as an intravenous infusion of 10 mg/kg within 10 minutes (loading dose) and before surgical incision, followed by 5 mg/kg/hour continuous maintenance infusion for the length of surgery (typically 4 to 8 hours). For example, an 80 kg patient would receive 800 mg prior to incision and a 400 mg/hour infusion for the duration of surgery. For a 6 hour procedure, the total dose administered would be 3200 mg.

Placebo arm: As there is no standard of care concerning administration of antifibrinolytic agents in cystectomy procedures, controls will follow the same dosing and schedule described above, but with 0.9% saline infusion.

Outcomes: The primary research objective is whether the use of systemic tranexamic acid compared to placebo reduces the proportion of radical cystectomy patients requiring red blood cell transfusion up to 30 days post-operative (from a 50% transfusion rate with placebo to 35% with tranexamic acid). Secondary questions are: Will use of systemic tranexamic acid compared to placebo result in reductions in: i) intraoperative blood loss, ii) amounts of transfused blood products, and iii) post-operative complications? The safety (thrombotic events) of tranexamic acid will also be evaluated.

Importance of this study: If tranexamic acid reduces the number of blood transfusions, there will be an immediate impact to cystectomy patients, and surgeons may consider the routine use of systemic tranexamic acid during similar abdomino-pelvic procedures associated with significant blood loss.

Conditions

Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Tranexamic Acid

Tranexamic acid will be administered as an intravenous infusion of 10 mg/kg over 10 minutes (loading dose) prior to surgical incision, followed by 5 mg/kg/hour continuous maintenance infusion for the length of surgery (typically 4 to 8 hours). For example, an 80 kg patient would receive 800 mg prior to incision and a 400 mg/hr infusion for the duration of surgery. For a 6 hour procedure, the total dose administered would be 3200 mg.

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

Tranexamic acid will be administered as an intravenous infusion of 10 mg/kg over 10 minutes (loading dose) prior to surgical incision, followed by 5 mg/kg/hour continuous maintenance infusion for the length of surgery (typically 4 to 8 hours).

Placebo control

As there is no standard of care concerning administration of anti-fibrinolytic agents in cystectomy procedures, controls will follow the same dosing and schedule as above (loading dose followed by maintenance infusion), but with 0.9% sodium chloride.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

As there is no standard of care concerning administration of anti-fibrinolytic agents in cystectomy procedures, controls will follow the same dosing and schedule as above (loading dose followed by maintenance infusion), but with 0.9% sodium chloride.

Interventions

Tranexamic Acid

Tranexamic acid will be administered as an intravenous infusion of 10 mg/kg over 10 minutes (loading dose) prior to surgical incision, followed by 5 mg/kg/hour continuous maintenance infusion for the length of surgery (typically 4 to 8 hours).

Intervention Type: DRUG

Placebo

As there is no standard of care concerning administration of anti-fibrinolytic agents in cystectomy procedures, controls will follow the same dosing and schedule as above (loading dose followed by maintenance infusion), but with 0.9% sodium chloride.

Intervention Type: DRUG

Other Intervention Names

Cyklokapron (Pfizer); Normal Saline

Eligibility Criteria

Inclusion Criteria

• Participant ≥ 18 years at time of consent
• Participant has bladder cancer and will undergo radical cystectomy to remove bladder
• Participant is willing to receive blood products (i.e. packed red blood cells, platelets, plasma)
• Have obtained Informed Consent

Exclusion Criteria

• Participant declines consent
• Participants incapable (incompetent) of providing Informed Consent
• Participant is under 18 years
• Participant is unwilling to receive blood products due to personal reasons
• Participant has thromboembolic disease (active or diagnosed within 1 year) such as deep vein thrombosis, pulmonary embolism or cerebral thrombosis)
• Participant with known personal history of subarachnoid haemorrhage.
• Participant has acquired disturbances to his / her colour vision (does not apply to congenital colour blindness)
• Participant is pregnant (confirmed by βHCG test)
• Participant has a known allergy to tranexamic acid

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Dalhousie University

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: collaborator

University of Western Ontario, Canada

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rodney H Breau, MD, FRCSC

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Northern Alberta Urology Centre

Edmonton, Alberta, Canada

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

London Health Sciences Complex (LHSC)

London, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

Centre Hospitalier de l'Université de Québec (CHUQ)

Québec, , Canada

Countries

Canada

References

Breau RH, Lavallee LT, Cagiannos I, Momoli F, Bryson GL, Kanji S, Morash C, Turgeon AF, Zarychanski R, Houston BL, McIsaac DI, Mallick R, Knoll GA, Kulkarni G, Izawa J, Saad F, Kassouf W, Fradet V, Rendon R, Shayegan B, Fairey A, Drachenberg DE, Fergusson D. Tranexamic Acid During Radical Cystectomy: A Randomized Clinical Trial. JAMA Surg. 2024 Dec 1;159(12):1355-1363. doi: 10.1001/jamasurg.2024.4183.

Reference Type: DERIVED

PMID: 39356537 (View on PubMed)

Breau RH, Lavallee LT, Cnossen S, Witiuk K, Cagiannos I, Momoli F, Bryson G, Kanji S, Morash C, Turgeon A, Zarychanski R, Mallick R, Knoll G, Fergusson DA. Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial. Trials. 2018 May 2;19(1):261. doi: 10.1186/s13063-018-2626-3.

Reference Type: DERIVED

PMID: 29716640 (View on PubMed)

Related Links

https://www.pfizer.ca/cyklokapron-tranexamic-acid

Tranexamic Acid (Cyklokapron) Product Monograph

Other Identifiers

Control # 162042

Identifier Type: OTHER

Identifier Source: secondary_id

CIHR MOP-342559

Identifier Type: -

Identifier Source: org_study_id