Back to resultsDEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION)
Primary Purpose
Bleeding, Surgical Blood Loss, Seizures
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tranexamic Acid
Sponsored by
About this trial
This is an interventional prevention trial for Bleeding focused on measuring Tranexamic Acid, On-pump Cardiac Surgery
Eligibility Criteria
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):
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
Sites / Locations
- Kelowna General HospitalRecruiting
- St. Boniface HospitalRecruiting
- Saint John Regional HospitalRecruiting
- Hamilton Health Sciences - General HospitalRecruiting
- CHUMRecruiting
- Montreal Heart InstituteRecruiting
- IUCPQRecruiting
- Petrovsky National Research CentreRecruiting
- E.Meshalkin National Medical Research CenterRecruiting
- Saint-Petersburg State University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Topical Tranexamic Acid/Placebo
Intravenous Tranexamic Acid/Placebo
Arm Description
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 1 to 10g (10 to 100mL) or placebo administered intravenously at the induction of anesthesia as a bolus-infusion.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT03954314
First Posted
May 15, 2019
Last Updated
February 7, 2023
Sponsor
Population Health Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT03954314
Brief Title
DEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
Acronym
DEPOSITION
Official Title
Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 17, 2019 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Population Health Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bleeding, Surgical Blood Loss, Seizures
Keywords
Tranexamic Acid, On-pump Cardiac Surgery
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
3800 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Topical Tranexamic Acid/Placebo
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intravenous Tranexamic Acid/Placebo
Arm Type
Active Comparator
Arm Description
Intravenous Tranexamic Acid 1 to 10g (10 to 100mL) or placebo administered intravenously at the induction of anesthesia as a bolus-infusion.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid
Other Intervention Name(s)
Cyklokapron
Intervention Description
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.
Primary Outcome Measure Information:
Title
The proportion of patients experiencing an in-hospital seizure
Description
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.
Time Frame
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Secondary Outcome Measure Information:
Title
The proportion of patients in-hospital who receive red blood cell transfusions
Description
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.
Time Frame
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Other Pre-specified Outcome Measures:
Title
Blood product transfusions
Description
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.
Time Frame
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Title
Re-operation for bleeding or tamponade
Description
Analyzed with a binomial regression
Time Frame
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
Title
Duration of ICU stay
Description
Analyzed using an ANCOVA model.
Time Frame
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.
Title
MACE (Death, non-fatal Myocardial Infarction (MI), or non-fatal stroke)
Description
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).
Time Frame
Start of surgery to hospital discharge or 10 days maximum (whichever occurs first)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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):
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ingrid Copland, CCRA
Phone
905-527-4322
Ext
40368
Email
cogency@phri.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Austin Browne, PhD
Phone
905-527-4322
Ext
40582
Email
Austin.Browne@phri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andre Lamy, MD
Organizational Affiliation
Population Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kelowna General Hospital
City
Kelowna
State/Province
British Columbia
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Coleen Adderley
First Name & Middle Initial & Last Name & Degree
Ahmad Poostizadeh, MD
Facility Name
St. Boniface Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rakesh Arora, Dr.
Facility Name
Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 4L2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Craig Brown, Dr.
Facility Name
Hamilton Health Sciences - General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Power
Phone
905-521-2100
Ext
44495
Email
powerpat@hhsc.ca
First Name & Middle Initial & Last Name & Degree
Andre Lamy, MD, MHSc
Facility Name
CHUM
City
Montreal
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Josee Bernardi
First Name & Middle Initial & Last Name & Degree
Nicolas Noiseux, MD
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 1C8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Demers, Dr.
Facility Name
IUCPQ
City
Quebec City
State/Province
Quebec
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valerie Morin
First Name & Middle Initial & Last Name & Degree
Frederic Jacques, MD
Facility Name
Petrovsky National Research Centre
City
Moscow
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Artem Gubko, MD
First Name & Middle Initial & Last Name & Degree
Boris Akselrod, MD
Facility Name
E.Meshalkin National Medical Research Center
City
Novosibirsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dmitry Sirota, MD
Facility Name
Saint-Petersburg State University Hospital
City
Saint-Petersburg
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elina Karnaukhova
First Name & Middle Initial & Last Name & Degree
Sergey Efremov, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28858904
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.
Results Reference
background
PubMed Identifier
21983111
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.
Results Reference
background
PubMed Identifier
30908754
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.
Results Reference
result
PubMed Identifier
27774838
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. Erratum In: N Engl J Med. 2018 Feb 22;378(8):782.
Results Reference
result
PubMed Identifier
18480196
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. Erratum In: N Engl J Med. 2010 Sep 23;363(13):1290.
Results Reference
result
PubMed Identifier
30146969
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.
Results Reference
result
PubMed Identifier
22054656
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.
Results Reference
result
Learn more about this trial
DEPOSITION - Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
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