Clinical trial NCT03954314: DEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
Official title: Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bleeding
Surgical Blood Loss
Seizures
Keywords: Tranexamic Acid
On-pump Cardiac Surgery
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2019-05-17
Enrollment: 3242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The proportion of patients experiencing an in-hospital seizure
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Secondary outcomes:
measure: The proportion of patients in-hospital who receive red blood cell transfusions
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Other outcomes:
measure: Blood product transfusions
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Re-operation for bleeding or tamponade
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
measure: Duration of ICU stay
timeFrame: 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.
measure: MACE (Death, non-fatal Myocardial Infarction (MI), or non-fatal stroke)
timeFrame: Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Locations:
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - General Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS NIM/Hôpital Sacré-Coeur de Montréal
state: Quebec
city: Quebec City
country: Canada
facility: IUCPQ
state: Quebec
city: Beijing
country: China
facility: Beijing Anzhen Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Třinec
country: Czechia
facility: Nemocnice Agel Třinec
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Moscow
country: Russian Federation
facility: Petrovsky National Research Centre
city: Novosibirsk
country: Russian Federation
facility: E.Meshalkin National Medical Research Center
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State University Hospital
Study officials:
affiliation: Population Health Research Institute
name: Andre Lamy, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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 Surg. 2019 May;34(5):305-311. doi: 10.1111/jocs.14027. Epub 2019 Mar 25.
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 Undergoing Coronary-Artery Surgery. N Engl J Med. 2017 Jan 12;376(2):136-148. doi: 10.1056/NEJMoa1606424. Epub 2016 Oct 23.
citation: 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 and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008 May 29;358(22):2319-31. doi: 10.1056/NEJMoa0802395. Epub 2008 May 14.
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, Bagshaw SM, Hwang NC, Royse C, Hall J, Dai D, Mistry N, Thorpe K, Verma S, Juni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery. N Engl J Med. 2018 Sep 27;379(13):1224-1233. doi: 10.1056/NEJMoa1808561. Epub 2018 Aug 26.
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 Nov 4.