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

NCT03954314 | Terminated Phase 3 DMC

• 1 other identifier: DEPOSITION
• Study Type: interventional
• Target: 3,242
• Locations: 6 countries
• Sites: 16

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.

Conditions

Bleeding; Surgical Blood Loss; Seizures

Keywords

Tranexamic Acid; On-pump Cardiac Surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• The proportion of patients in-hospital who receive red blood cell transfusions

  Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)

Other Outcomes (4)

• Blood product transfusions

  Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)

• Re-operation for bleeding or tamponade

  Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)

• Duration of ICU stay

  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.

Study Arms (2)

Topical Tranexamic Acid/Placebo

ACTIVE COMPARATOR

Topical Tranexamic Acid 5g to 10g (50 to 100mL) or placebo. The topical will be poured into the pericardial and mediastinal cavities after protamine administration.

Drug: Tranexamic Acid

Intravenous Tranexamic Acid/Placebo

ACTIVE COMPARATOR

Intravenous Tranexamic Acid 1 to 10g (10 to 100mL) or placebo administered intravenously at the induction of anesthesia as a bolus-infusion.

Drug: Tranexamic Acid

Interventions

Tranexamic Acid DRUG

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.

Also known as: Cyklokapron

Intravenous Tranexamic Acid/Placebo; Topical Tranexamic Acid/Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• 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
• Provide written informed consent

You may not qualify if:

• Allergy to tranexamic acid
• Undergoing minimally invasive surgery
• 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)
• History of previous cardiac surgery
• Estimated glomerular filtration rate \<30 mL/min (CKD-EPI equation) or on dialysis
• Pre-operative hemoglobin \> 170 g/L or \<110 g/L
• Pre-operative thrombocytopenia (\<50,000 platelets per µL)
• Expected circulatory arrest
• Pregnancy or breast feeding
• Previously enrolled in the DEPOSITION trial
• Refusal of blood products
• Pericardiectomy

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (16)

Kelowna General Hospital

Kelowna, British Columbia, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Hamilton Health Sciences - General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

CHUM

Montreal, Ontario, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

CIUSSS NIM/Hôpital Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Location

IUCPQ

Québec, Quebec, Canada

Location

Beijing Anzhen Hospital

Beijing, China

Location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

Nemocnice Agel Třinec

Třinec, Czechia

Location

University of Malaya

Kuala Lumpur, Malaysia

Location

Auckland City Hospital

Auckland, New Zealand

Location

Petrovsky National Research Centre

Moscow, Russia

Location

E.Meshalkin National Medical Research Center

Novosibirsk, Russia

Location

Saint-Petersburg State University Hospital

Saint Petersburg, Russia

Location

Related Publications (8)

• 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.

  PMID: 28858904 BACKGROUND

• 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.

  PMID: 21983111 BACKGROUND

• 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.

  PMID: 30908754 RESULT

• 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.

  PMID: 27774838 RESULT

• 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.

  PMID: 18480196 RESULT

• 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.

  PMID: 30146969 RESULT

• 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.

  PMID: 22054656 RESULT

• Lamy A, Sirota DA, Jacques F, Poostizadeh A, Noiseux N, Efremov S, Demers P, Akselrod B, Wang CY, Arora RC, Branny P, McGuinness SP, Brown CD, Jeanmart H, Zhao Q, Zhang H, Belley-Cote EP, Whitlock RP, Browne A, Copland I, Vincent J, Khatun R, Balasubramanian K, Bangdiwala SI, McGillion MH, Fox-Robichaud AE, Spence J, Yusuf S, Devereaux PJ; DEPOSITION Study Group. Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial. Circulation. 2024 Oct 22;150(17):1315-1323. doi: 10.1161/CIRCULATIONAHA.124.069606. Epub 2024 Apr 8.

  PMID: 38587333 DERIVED

MeSH Terms

Conditions

Hemorrhage; Blood Loss, Surgical; Seizures

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Andre Lamy, MD

  Population Health Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacy will prepare 2 syringes of 50 ml of topical TxA (5 g) or placebo. They will also prepare for the same patient 2 syringes of 50 ml (5 g) for intravenous (i.v.) injection or placebo. TxA is similar in all aspects to normal saline. Blinding of both teams will be easy. The syringes will be prepared and randomized in pharmacy before the surgery.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 17, 2019
• Study Start: September 17, 2019
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); CZ (1); CN (2); CA (8); MY (1); RU (3)