Clinical trial NCT04537533: Tranexamic Acid Infusion in Low Dose Versus in High Dose for Reducing Blood Loss in Radical Cystectomy Operations
Official title: Intraoperative Tranexamic Acid Infusion in Low Dose Versus in High Dose for Reducing Blood Loss and Its Effect on Postoperative Thromboembolic Complications in Radical Cystectomy Operations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Bleeding
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-09-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Bladder cancer is one of the most common cancers of the genitourinary tract in adults, and its incidence distinctly increases with age . In almost two-thirds of cases, the disease is superficial at presentation and involves the mucosal and sub mucosal layers or the lamina propria of the bladder, whereas ∼20% to 30% of patients have muscle-invasive tumors. Superficial bladder cancer is treated by transurethral endoscopic resection, which can be followed by endovesical therapy for patients at risk of disease recurrence and progression . In contrast, muscle-invasive bladder cancer is generally treated by radical cystectomy with pelvic lymph node dissection and then creation of urinary diversion to create an alternate route for urine passage, which demonstrates 10-year recurrence-free survival rates of 50% to 59% and overall survival rates of ∼45% .

These major surgeries have a prolonged operative times and are associated with significant risk of complications including high risk of perioperative bleeding and subsequent need for blood transfusion with significant postoperative complications, which are reportedly in the range of 24% to 64% .

Detailed description: Among individual surgeons at institutions that perform many procedures, median intraoperative blood loss is between 600 and 1700 mL. The incidence of at least one intraoperative blood transfusion is 9 to 67%, and the postoperative transfusion risk is at least 15%. Among cystectomy patients who receive transfusion, a median of 2 units of blood cells are given. Therefore, it is very important to establish surgical and anesthetic protocols aimed at minimizing intraoperative blood loss and subsequent blood transfusion requirements in order to improve postoperative outcomes.

Venous thromboembolism (VTE) in radical cystectomy can account for up to 22% of total deaths after surgery . In the bladder cancer literature, symptomatic thromboembolic events occur in up to 8.3% of patients , but subclinical deep vein thrombosis (DVT) rates can be as high as 24.4% when examining an ultrasonography (US)-screened population . In fact, undergoing a RC is a significant, independent risk factor on multivariable analysis for developing a deep venous thrombosis.

Lysine analog drugs are synthetic derivatives of the amino acid lysine that reversibly block lysine-binding sites on plasminogen molecules. This action prevents the conversion of plasminogen to plasmin, the active enzyme that degrades fibrin clots. Therefore, lysine analogs decrease the breakdown of clots and are considered anti-fibrinolytics. There are two commonly studied lysine analogs, tranexamic acid and epsilon-aminocaproic acid. Both of these drugs have been shown to decrease blood loss and blood transfusion need during some surgeries without a significant increase in adverse events.

Eligibility criteria: Inclusion Criteria:

* Age: 18 - 70 years old
* Gender: Males and females
* ASA grade I - II
* Patients undergoing radical cystectomy for bladder cancer regardless of tumor stage and histology.
* Patients who have undergone previous surgery, radiation, or chemotherapy may be included.
* All forms of urinary diversion are allowed

Exclusion Criteria:

* Patient refusal.
* Patient with allergy to tranexamic acid.
* Patients have thromboembolic disease (active or diagnosed within 1 year), such as deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral thrombosis or MI.
* Pregnancy.
* Patients with hematuria.

Primary outcomes:
measure: Effect of low dose and high dose tranexemic acid infusion on Intraoperative blood loss .
timeFrame: within the first 15 days
Secondary outcomes:
measure: Postoperative thromboembolic events
timeFrame: within the first 15 days
Other outcomes:
Locations:
Study officials:
References:
citation: van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, Witjes JA, Zlotta AR. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009 Sep;56(3):430-42. doi: 10.1016/j.eururo.2009.06.028. Epub 2009 Jun 26.
citation: Parkin DM. The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl. 2008 Sep;(218):12-20. doi: 10.1080/03008880802285032.
citation: Thompson E. Urological oncology in Europe. Research highlights from the XVIIth congress of the European Association of Urology, Birmingham, UK, February 23-26, 2002. Drugs Today (Barc). 2002 Apr;38(4):221-34. No abstract available.
citation: Meyer JP, Blick C, Arumainayagam N, Hurley K, Gillatt D, Persad R, Fawcett D. A three-centre experience of orthotopic neobladder reconstruction after radical cystectomy: revisiting the initial experience, and results in 104 patients. BJU Int. 2009 Mar;103(5):680-3. doi: 10.1111/j.1464-410X.2008.08204.x. Epub 2008 Dec 2.
citation: Cookson MS, Chang SS, Wells N, Parekh DJ, Smith JA Jr. Complications of radical cystectomy for nonmuscle invasive disease: comparison with muscle invasive disease. J Urol. 2003 Jan;169(1):101-4. doi: 10.1016/S0022-5347(05)64045-1.
citation: Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Mansson W, Sagalowsky A, Wirth MP. Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol. 2010 Jun;57(6):983-1001. doi: 10.1016/j.eururo.2010.02.024. Epub 2010 Feb 26.
citation: Lowrance WT, Rumohr JA, Chang SS, Clark PE, Smith JA Jr, Cookson MS. Contemporary open radical cystectomy: analysis of perioperative outcomes. J Urol. 2008 Apr;179(4):1313-8; discussion 1318. doi: 10.1016/j.juro.2007.11.084. Epub 2008 Mar 4.
citation: Chang SS, Smith JA Jr, Wells N, Peterson M, Kovach B, Cookson MS. Estimated blood loss and transfusion requirements of radical cystectomy. J Urol. 2001 Dec;166(6):2151-4.
citation: Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, Raj G, Bochner BH, Dalbagni G, Herr HW, Donat SM. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009 Jan;55(1):164-74. doi: 10.1016/j.eururo.2008.07.031. Epub 2008 Jul 18.
citation: Novara G, De Marco V, Aragona M, Boscolo-Berto R, Cavalleri S, Artibani W, Ficarra V. Complications and mortality after radical cystectomy for bladder transitional cell cancer. J Urol. 2009 Sep;182(3):914-21. doi: 10.1016/j.juro.2009.05.032. Epub 2009 Jul 17.
citation: Hautmann RE, de Petriconi RC, Volkmer BG. Lessons learned from 1,000 neobladders: the 90-day complication rate. J Urol. 2010 Sep;184(3):990-4; quiz 1235. doi: 10.1016/j.juro.2010.05.037.
citation: Quek ML, Stein JP, Daneshmand S, Miranda G, Thangathurai D, Roffey P, Skinner EC, Lieskovsky G, Skinner DG. A critical analysis of perioperative mortality from radical cystectomy. J Urol. 2006 Mar;175(3 Pt 1):886-9; discussion 889-90. doi: 10.1016/S0022-5347(05)00421-0.
citation: Clement C, Rossi P, Aissi K, Barthelemy P, Guibert N, Auquier P, Ragni E, Rossi D, Frances Y, Bastide C. Incidence, risk profile and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery. J Urol. 2011 Dec;186(6):2293-7. doi: 10.1016/j.juro.2011.07.074. Epub 2011 Oct 20.
citation: Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol). 1980;14:41-7. No abstract available.