DEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery

Bleeding Clinical Trial

— DEPOSITION  

Official title:

Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03954314
• Other study ID #: DEPOSITION
• Status: Terminated
• Phase: Phase 3
• Start date: September 17, 2019
• Est. completion date: November 28, 2023

Study information

• Verified date: December 2023
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim is to conduct a double-dummy multi-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TxA) versus the usual intravenous TxA in patients undergoing on-pump cardiac surgery.

Description:

Postoperative bleeding related to open cardiac surgery increases the rates of complications and mortality. It results from the blood thinners that are needed for use. Intravenous tranexamic acid (TxA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TxA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TxA and the brain tissues. The aim is to eliminate the risk of seizures but to maintain the protection against bleeding. When TxA is used directly on the tissues (topically) for other type of surgeries (joints), TxA is effective to reduce blood loss and transfusions. The aim is to prove that direct application of TxA on the heart can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3242
• Est. completion date: November 28, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. = 18 years of age

2. Undergoing a cardiac surgical procedure (i.e. isolated coronary artery bypass graft (CABG), isolated single cardiac valve surgery or a combination of both or isolated ascending aorta replacement) with the use of cardiopulmonary bypass (CPB) and median sternotomy

3. Provide written informed consent

Exclusion Criteria:

1. Allergy to tranexamic acid

2. Undergoing minimally invasive surgery

3. Fulfill any of the following transfusion risk factors (A-D):

A. Emergency surgery B. History of bleeding disorder C. Inherited thromboembolic or hemorrhagic disease D. Infective endocarditis (active)

4. History of previous cardiac surgery

5. Estimated glomerular filtration rate <30 mL/min (CKD-EPI equation) or on dialysis

6. Pre-operative hemoglobin > 170 g/L or <110 g/L

7. Pre-operative thrombocytopenia (<50,000 platelets per µL)

8. Expected circulatory arrest

9. Pregnancy or breast feeding

10. Previously enrolled in the DEPOSITION trial

11. Refusal of blood products

12. Pericardiectomy

Related Conditions & MeSH terms

• Bleeding
• Blood Loss, Surgical
• Hemorrhage
• Postoperative Hemorrhage
• Seizures
• Surgical Blood Loss

Intervention

Drug:
• Tranexamic Acid
Tranexamic Acid is a medication used to treat or prevent excessive blood loss from major trauma, post partum, surgery, tooth removal, nose bleeds, and heavy menstruation.

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences - General Hospital	Hamilton	Ontario
Canada	Kelowna General Hospital	Kelowna	British Columbia
Canada	CHUM	Montreal	Ontario
Canada	CIUSSS NIM/Hôpital Sacré-Coeur de Montréal	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	IUCPQ	Quebec City	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	St. Boniface Hospital	Winnipeg	Manitoba
China	Beijing Anzhen Hospital	Beijing
China	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai
Czechia	Nemocnice Agel Trinec	Trinec
Malaysia	University of Malaya	Kuala Lumpur
New Zealand	Auckland City Hospital	Auckland
Russian Federation	Petrovsky National Research Centre	Moscow
Russian Federation	E.Meshalkin National Medical Research Center	Novosibirsk
Russian Federation	Saint-Petersburg State University Hospital	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Countries where clinical trial is conducted

Canada,  China,  Czechia,  Malaysia,  New Zealand,  Russian Federation, 

References & Publications (7)

Fergusson DA, Hebert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussieres JS, Cote D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R; BART Investigators. A comparison of aprotinin — View Citation

Habbab LM, Hussain S, Power P, Bashir S, Gao P, Semelhago L, VanHelder T, Parry D, Chu V, Lamy A. Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study. J Card S — View Citation

Kalavrouziotis D, Voisine P, Mohammadi S, Dionne S, Dagenais F. High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg. 2012 Jan;93(1):148-54. doi: 10.1016/j.athoracsur.2011.07.085. Epub 2011 N — View Citation

Lamy A, Tong W, Gao P, Chrolavicius S, Gafni A, Yusuf S, Connolly SJ. The cost of clopidogrel use in atrial fibrillation in the ACTIVE-A trial. Can J Cardiol. 2012 Jan-Feb;28(1):95-101. doi: 10.1016/j.cjca.2011.08.112. Epub 2011 Oct 8. — View Citation

Mazer CD, Whitlock RP, Fergusson DA, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, Carrier FM, McGuinness S, Young PJ, Byrne K, Villar JC, Royse A, Grocott HP, Seeberger MD, Mehta C, Lellouche F, Hare GMT, Painter TW, Fremes S, Syed S, — View Citation

Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussieres JS, McGuinness S, Byrne K, Chan MT, Landoni G, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic Acid in Patients Und — View Citation

Spence J, Long S, Tidy A, Raymer K, Devereaux PJ, Lamy A, Whitlock R, Syed S. Tranexamic Acid Administration During On-Pump Cardiac Surgery: A Survey of Current Practices Among Canadian Anesthetists Working in Academic Centers. Anesth Analg. 2017 Dec;125(6):1863-1870. doi: 10.1213/ANE.0000000000002422. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood product transfusions	Analyzed using an ANCOVA model. In such a model, bags of blood product will be included as a dependent variable, whereas dose of tranexamic acid and treatment will be included as covariates.	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Other	Re-operation for bleeding or tamponade	Analyzed with a binomial regression	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Other	Duration of ICU stay	Analyzed using an ANCOVA model.	Number of hours in ICU are being collected at the Post-Operative Visit. Hour collection will start upon arrival at ICU post surgery and stop at ICU exit, up to 10 days maximum.
Other	MACE (Death, non-fatal Myocardial Infarction (MI), or non-fatal stroke)	A Cox proportional hazard model will be used to analyze the time to the first occurrence of the composite of death, non-fatal MI, or non-fatal stroke (MACE).	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Primary	The proportion of patients experiencing an in-hospital seizure	To determine in patients undergoing on-pump cardiac surgery, if topical tranexamic acid (intra-pericardial) is superior to the usual intravenous tranexamic acid administration for reducing the risk of in-hospital seizure.	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Secondary	The proportion of patients in-hospital who receive red blood cell transfusions	To determine in patients undergoing on-pump cardiac surgery, if topical tranexamic acid (intra-pericardial) compared with intravenous tranexamic acid administration is associated with a non-inferior risk of in-hospital red blood cell transfusion.	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)