BleedingPhase 4DEPOSITIONNCT03376061
Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
A Phase 4 study testing Tranexamic Acid in people with Bleeding and Surgical Blood Loss, run by Population Health Research Institute at 1 site in Canada.
Trial summary
The aim is to conduct a double-blinded single-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TA) versus the usual intravenous TA in patients undergoing cardiac surgery at the Hamilton General Hospital. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bleeding, Surgical Blood Loss
- What is being tested?
- Tranexamic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 1 siteCanada
- Study dates
- 21 Dec 2017to 4 Sep 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female >= 18 years old
- Undergoing cardiac surgical procedure with the use of cardiopulmonary bypass and median sternotomy
- Provide written informed consent
Who cannot join
- Poor (English) language comprehension
- Minimally invasive valve surgery
- Off-pump procedures
- Emergency operations
- Known history of increased bleeding disorder
- Thromboembolic disease
- Allergy to tranexamic acid
- Severe renal impairment (eGFR <30 mL/min/1.73m2 )
Trial locations and contacts
1 site in 1 country.
About this study
Official title: DEPOSITION: Pilot Study Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
The aim is to conduct a double-blinded single-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TA) versus the usual intravenous TA in patients undergoing cardiac surgery at the Hamilton General Hospital. This pilot study will assess the feasibility to perform a large randomized international trial exploring this objective.
Read the 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 (TA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TA and the brain tissues. The aim is to eliminate the risk of seizures but to maintain the protection against bleeding. When TA is used directly on the tissues (topically) for other type of surgeries (joints), TA is effective to reduce blood loss and transfusions. The aim is to prove that direct application of TA on the heart can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.
- Conditions
- Bleeding, Surgical Blood Loss
- Being tested
- Tranexamic Acid
- Keywords
- Tranexamic Acid, Cardiac surgery
- Medical subject headings
- Hemorrhage, Blood Loss, Surgical
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic AcidDrug
Also called Cyklokapron
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.
| Study group | Role | What they receive |
|---|---|---|
| TA Topical | Active comparator | 1 syringe of 50ml of topical Tranexamic Acid (5g) or placebo. The topical will be poured into the pericardial mediastinal cavities in 2 equal doses, 25ml when the pt comes off-pump and the other 25ml before sternotomy is closed. Receives: Drug: Tranexamic Acid |
| TA Intravenous | Active comparator | 2 syringes of 50ml (5mg) Tranexamic Acid for intravenous injection or placebo. Receives: Drug: Tranexamic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Volume of Mediastinal Fluid Collected From Participants
Cumulative volume (mL) of fluid collected from mediastinal drainage tubes 24 hours after the surgical procedure
Measured: Fluid collected in the first 24 hours after the surgical procedure
Secondary outcomes (6)
Number of Participants With Seizures
Patients experiencing a post-operative seizure
Measured: Patients will be followed post-operatively until hospital discharge
Number of Participants With Mortality
The occurrence of death due to any cause
Measured: Patients will be followed post-operatively until hospital discharge
Number of Participants With RBC Transfusion
Patients requiring a red blood cell transfusion
Measured: Intra-operative and post-operative RBC transfusions
Number of Participants With Re-operation for Bleeding or Tamponade
Occurrence of re-operation for the purpose of bleeding or cardiac tamponade
Measured: Patients will be followed post-operatively until hospital discharge
Median Number of Hours Participants Spent in ICU
Number of hours participants spent in the intensive care unit (ICU)
Measured: Number of hours spent in ICU from arrival to exit (collected at the Post-Operative Visit).
Mean Concentration of TxA in Plasma Collected From Participants
Plasma TxA concentrations measured from blood samples taken upon arrival in the ICU
Measured: on arrival in ICU within 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2017
- Study start21 Dec 2017
- Primary completion4 Sep 2018
- Study completion4 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andre Lamy, MD MHSc, Principal investigator, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03376061
- Sponsor's protocol ID
- DEPOSITION 1.0 2017-07-28
- Acronym
- DEPOSITION
- Status last verified
- Jan 2021
- First submitted
- 17 Nov 2017
- Last updated
- 11 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kucuk O, Kwaan HC, Frederickson J, Wade L, Green D. Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol. 1986 Nov;23(3):223-9. doi: 10.1002/ajh.2830230306.
PubMed 3766524Harker LA, Malpass TW, Branson HE, Hessel EA 2nd, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood. 1980 Nov;56(5):824-34. No abstract available.
PubMed 6448643Despotis GJ, Santoro SA, Spitznagel E, Kater KM, Cox JL, Barnes P, Lappas DG. Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg. 1994 Jan;107(1):271-9.
PubMed 8283896Lemmer JH Jr, Stanford W, Bonney SL, Breen JF, Chomka EV, Eldredge WJ, Holt WW, Karp RB, Laub GW, Lipton MJ, et al. Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study. J Thorac Cardiovasc Surg. 1994 Feb;107(2):543-51; discussion 551-3.
PubMed 7508070Santos AT, Kalil RA, Bauemann C, Pereira JB, Nesralla IA. A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting. Braz J Med Biol Res. 2006 Jan;39(1):63-9. doi: 10.1590/s0100-879x2006000100007. Epub 2005 Dec 15.
PubMed 16400465Pleym H, Stenseth R, Wahba A, Bjella L, Karevold A, Dale O. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg. 2003 Apr;96(4):923-928. doi: 10.1213/01.ANE.0000054001.37346.03.
PubMed 12651635Myles 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.
PubMed 27774838Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg. 2008 Dec;107(6):1783-90. doi: 10.1213/ane.0b013e318184bc20.
PubMed 19020118Kalavrouziotis 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.
PubMed 22054656
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DEPOSITION: Pilot Study Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
- ClinicalTrials.gov ID
- NCT03376061
- Acronym / sponsor ID
- DEPOSITION / DEPOSITION 1.0 2017-07-28
- Conditions
- Bleeding, Surgical Blood Loss
- Keywords
- Tranexamic Acid, Cardiac surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- 21 Dec 2017 (actual)
- Primary completion
- 4 Sep 2018 (actual)
- Study completion
- 4 Sep 2018 (actual)
- First posted
- 18 Dec 2017 (actual)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim is to conduct a double-blinded single-centre randomized controlled clinical trial of application of topical dose of tranexamic acid (TA) versus the usual intravenous TA in patients undergoing cardiac surgery at the Hamilton General Hospital. This pilot study will assess the feasibility to perform a large randomized international trial exploring this objective.
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 (TA) has become a mainstay in cardiac surgical procedures for decreasing bleeding and minimizing transfusion requirements. Although intravenous TA is usually well tolerated, there is a well-known risk (1 to 4%) of postoperative seizures. This is due to the similarity between TA and the brain tissues. The aim is to eliminate the risk of seizures but to maintain the protection against bleeding. When TA is used directly on the tissues (topically) for other type of surgeries (joints), TA is effective to reduce blood loss and transfusions. The aim is to prove that direct application of TA on the heart can eliminate postoperative seizures and reduce the amount of blood transfusions in patients who have cardiac surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
| Arm | Type | Receives |
|---|---|---|
| TA Topical | Active comparator | Drug: Tranexamic Acid1 syringe of 50ml of topical Tranexamic Acid (5g) or placebo. The topical will be poured into the pericardial mediastinal cavities in 2 equal doses, 25ml when the pt comes off-pump and the other 25ml before sternotomy is closed. |
| TA Intravenous | Active comparator | Drug: Tranexamic Acid2 syringes of 50ml (5mg) Tranexamic Acid for intravenous injection or placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female >= 18 years old
- Undergoing cardiac surgical procedure with the use of cardiopulmonary bypass and median sternotomy
- Provide written informed consent
Key exclusion criteria (8 listed)
- Poor (English) language comprehension
- Minimally invasive valve surgery
- Off-pump procedures
- Emergency operations
- Known history of increased bleeding disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic AcidAlso: CyklokapronTranexamic 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. | Drug | TA Intravenous, TA Topical |
Primary outcome
Median Volume of Mediastinal Fluid Collected From Participants
Time frame: Fluid collected in the first 24 hours after the surgical procedure
Cumulative volume (mL) of fluid collected from mediastinal drainage tubes 24 hours after the surgical procedure
6 secondary outcomes
Number of Participants With Seizures
Time frame: Patients will be followed post-operatively until hospital discharge
Number of Participants With Mortality
Time frame: Patients will be followed post-operatively until hospital discharge
Number of Participants With RBC Transfusion
Time frame: Intra-operative and post-operative RBC transfusions
Number of Participants With Re-operation for Bleeding or Tamponade
Time frame: Patients will be followed post-operatively until hospital discharge
Median Number of Hours Participants Spent in ICU
Time frame: Number of hours spent in ICU from arrival to exit (collected at the Post-Operative Visit).
Mean Concentration of TxA in Plasma Collected From Participants
Time frame: on arrival in ICU within 3 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3766524Kucuk O, Kwaan HC, Frederickson J, Wade L, Green D. Increased fibrinolytic activity in patients undergoing cardiopulmonary bypass operation. Am J Hematol. 1986 Nov;23(3):223-9. doi: 10.1002/ajh.2830230306.
- Background: PubMed 6448643Harker LA, Malpass TW, Branson HE, Hessel EA 2nd, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood. 1980 Nov;56(5):824-34. No abstract available.
- Background: PubMed 8283896Despotis GJ, Santoro SA, Spitznagel E, Kater KM, Cox JL, Barnes P, Lappas DG. Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg. 1994 Jan;107(1):271-9.
- Background: PubMed 7508070Lemmer JH Jr, Stanford W, Bonney SL, Breen JF, Chomka EV, Eldredge WJ, Holt WW, Karp RB, Laub GW, Lipton MJ, et al. Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study. J Thorac Cardiovasc Surg. 1994 Feb;107(2):543-51; discussion 551-3.
- Background: PubMed 16400465Santos AT, Kalil RA, Bauemann C, Pereira JB, Nesralla IA. A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting. Braz J Med Biol Res. 2006 Jan;39(1):63-9. doi: 10.1590/s0100-879x2006000100007. Epub 2005 Dec 15.
- Background: PubMed 12651635Pleym H, Stenseth R, Wahba A, Bjella L, Karevold A, Dale O. Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg. 2003 Apr;96(4):923-928. doi: 10.1213/01.ANE.0000054001.37346.03.
- Background: PubMed 27774838Myles 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.
- Background: PubMed 19020118Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg. 2008 Dec;107(6):1783-90. doi: 10.1213/ane.0b013e318184bc20.
- Background: PubMed 22054656Kalavrouziotis 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andre Lamy, MD MHSc principal investigator
Population Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tranexamic Acid in people with Bleeding and Surgical Blood Loss, run by Population Health Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Volume of Mediastinal Fluid Collected From Participants (time frame: Fluid collected in the first 24 hours after the surgical procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03376061, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2021.