Tranexamic Acid Infusion in Low Dose Versus in High Dose for Reducing Blood Loss in Radical Cystectomy Operations

Bleeding Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04537533
• Other study ID #: BRC
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 2020
• Est. completion date: March 2022

Study information

• Verified date: August 2020
• Source: Assiut University
• Contact: Mohamed Reda Abdelaziz, Professor
• Phone: 01003919165
• Email: mohamed.hassan19[@]med.au.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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% .

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: March 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bleeding
• Hemorrhage

Intervention

Drug:
• Tranexamic acid
Intraoperative infusion

Other:
• Normal saline
intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (14)

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. — View Citation

Clément 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. — View 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. — View 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. — View Citation

Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Månsson 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. Review. — View 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. — View 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. — View Citation

Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. J Clin Pathol Suppl (R Coll Pathol). 1980;14:41-7. Review. — View 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. — View Citation

Parkin DM. The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl. 2008 Sep;(218):12-20. Review. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of low dose and high dose tranexemic acid infusion on Intraoperative blood loss .	Estimated Blood Loss and perioperative need for blood transfusion within the first 15 days .	within the first 15 days
Secondary	Postoperative thromboembolic events	Post operative complications as deep venous thrombosis, pulmonary embolism, MI, cerebral stroke, blurred vision and seizures within the first 15 days .	within the first 15 days