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

Sponsor

Population Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03954314

Collaborator

(none)

3,800

Enrollment

Locations

Arms

53.5

Anticipated Duration (Months)

542.9

Patients Per Site

10.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bleeding Surgical Blood Loss Seizures	Drug: Tranexamic Acid	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

3800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topicalTranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 17, 2019

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Topical Tranexamic Acid/Placebo 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 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. Other Names: Cyklokapron
Active Comparator: Intravenous Tranexamic Acid/Placebo 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 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. Other Names: Cyklokapron

Arm

Intervention/Treatment

Active Comparator: Topical Tranexamic Acid/Placebo

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

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.

Other Names:

Cyklokapron

Active Comparator: Intravenous Tranexamic Acid/Placebo

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

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.

Other Names:

Cyklokapron

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

Blood product transfusions [Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)]
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.
Re-operation for bleeding or tamponade [Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)]
Analyzed with a binomial regression
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.]
Analyzed using an ANCOVA model.
MACE (Death, non-fatal Myocardial Infarction (MI), or non-fatal stroke) [Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 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

Exclusion Criteria:

Allergy to tranexamic acid
Undergoing minimally invasive surgery
Fulfill any of the following transfusion risk factors (A-D):

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kelowna General Hospital	Kelowna	British Columbia	Canada
2	Hamilton Health Sciences - General Hospital	Hamilton	Ontario	Canada	L8L 2X2
3	CHUM	Montreal	Ontario	Canada
4	IUCPQ	Quebec City	Quebec	Canada
5	Petrovsky National Research Centre	Moscow		Russian Federation
6	E.Meshalkin National Medical Research Center	Novosibirsk		Russian Federation
7	Saint-Petersburg State University Hospital	Saint-Petersburg		Russian Federation