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

Phase 3

Terminated

• Conditions: Bleeding; Surgical Blood Loss; Seizures
• Interventions: Drug: Tranexamic Acid

• Registration Number: NCT03954314
• Lead Sponsor: Population Health Research Institute

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.

Study Timeline

• Study First Submitted: 2019-05-15
• Study First Submitted QC: 2019-05-15
• Study First Posted: 2019-05-17
• Study Start: 2019-09-17
• Primary Completion: 2023-11-28
• Study Completion: 2023-11-28
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3242

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
The proportion of patients experiencing an in-hospital seizure	Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)	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.

Secondary Outcome Measures

Name	Time	Method
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)	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.

Trial Locations

Locations (16)

Kelowna General Hospital; 🇨🇦 Kelowna, British Columbia, Canada

Hamilton Health Sciences - General Hospital; 🇨🇦 Hamilton, Ontario, Canada

St. Boniface Hospital; 🇨🇦 Winnipeg, Manitoba, Canada

Beijing Anzhen Hospital; 🇨🇳 Beijing, China

Saint John Regional Hospital; 🇨🇦 Saint John, New Brunswick, Canada

IUCPQ; 🇨🇦 Quebec City, Quebec, Canada

Montreal Heart Institute; 🇨🇦 Montreal, Quebec, Canada

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China

University of Malaya; 🇲🇾 Kuala Lumpur, Malaysia

Nemocnice Agel Třinec; 🇨🇿 Třinec, Czechia

CIUSSS NIM/Hôpital Sacré-Coeur de Montréal; 🇨🇦 Montreal, Quebec, Canada

CHUM; 🇨🇦 Montreal, Ontario, Canada

Petrovsky National Research Centre; 🇷🇺 Moscow, Russian Federation

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

E.Meshalkin National Medical Research Center; 🇷🇺 Novosibirsk, Russian Federation

Saint-Petersburg State University Hospital; 🇷🇺 Saint-Petersburg, Russian Federation