Coronary Artery DiseasePhase 3NCT01519245
Topical Application of Tranexamic Acid to Reduce Post-operative Bleeding in Coronary Artery Bypass Surgery
A Phase 3 study testing Tranexamic Acid and normal saline in people with Coronary Artery Disease, run by University of Saskatchewan.
Trial summary
The goal of this project is to determine whether the use of tranexamic acid, a clot-promoting drug, applied topically over the heart in coronary artery bypass graft surgery (CABG) will reduce post operative blood loss. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Tranexamic Acid and normal saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- Dec 2011to Jun 2012
- Phase
- Phase 3
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients scheduled for elective or urgent CABG of two to six vessels
Who cannot join
- Preoperative:
- Hemoglobin of less than 110g/L
- Under 18 years of age
- Body mass less than 75kg
- Presence of an intra-aortic balloon pump
- Emergency surgery, requiring operative intervention within 24 hours of consultation to the cardiac surgery team
Show all 20Show fewer
- Need for cardiac surgical intervention in addition to planned CABG (with the exception of patent foramen ovale closure)
- Ejection fraction (EF) of less than 50%, as determined by echocardiogram or angiography
- Pulmonary hypertension with pulmonary artery pressures greater than 60mmHg (as estimated by right ventricular systolic pressure (RVSP))
- Presence of infectious endocarditis
- Hepatic failure with impaired liver function, including International Normalized Ratio (INR) greater than 1.5
- Known diagnosed bleeding disorder
- History of heparin induced thrombocytopenia and thrombosis (HITT)
- Renal failure with pre-operative creatinine greater than 200ml/min or oliguria with urine output less than 10ml/hour
- Allergy to tranexamic acid
- Pregnancy
- Intraoperative:
- Discovery of infectious endocarditis
- Need for cardiac surgical intervention in addition to planned coronary CABG
- Development of allergic reaction to tranexamic acid following intravenous infusion
About this study
The goal of this project is to determine whether the use of tranexamic acid, a clot-promoting drug, applied topically over the heart in coronary artery bypass graft surgery (CABG) will reduce post operative blood loss. The investigators' hypothesis is that the use of a tranexamic acid-containing cardiac bath prior to chest closure will result in a statistically significant reduction in blood loss and transfusion requirements in patients who undergo CABG.
Read the detailed description
Bleeding is expected during major surgeries. In patients who undergo CABG, the risk for bleeding is increased because of the need for intra-operative anticoagulation, or thinning, of patient blood. This anticoagulation is necessary to reduce the risk of thrombosis potentially precipitated by the cardiopulmonary bypass machine, which pumps blood throughout the body while the surgeon operates on the heart.
Strategies are currently used in the operating room to minimize blood loss and the need for allogenic blood transfusion during and after cardiac surgeries. These strategies include the use of intravenous antifibrinolytic agents, intra-operative red blood cell salvage devices, and topical fibrin sealants. Although the risk of infection from a blood transfusion is very small with modern methods of blood screening, the risk of developing a transfusion reaction is possible and not predictable. Therefore, it is preferred to avoid administering a blood transfusion unless absolutely necessary.
The use of topical antifibrinolytic agents has been explored to further reduce blood loss in cardiac surgery. Several trials have been published in the literature since 1993 evaluating the efficacy of various antifibrinolytic medications applied topically, as a cardiac bath, prior to chest closure in CABG patients to reduce post-operative blood loss and potential need for blood transfusion.
The applicability of the methodology utilized in these studies, however, is limited in the context of the current Canadian practices of cardiac surgery. Considerable differences in the perioperative strategies of these trials are seen, in comparison to current North American practices of cardiac surgery. These trials also compared use of topically applied antifibrinolytic agents, including the lysine analogue tranexamic acid, to a control in the absence of intravenous antifibrinolytic agents. The use of intravenous lysine analogues to reduce peri-operative bleeding has now become a near-standard of care in CABG patients.
Currently, the only available antifibrinolytic agent in Canada is the lysine analogue tranexamic acid. This drug is widely used administered as an intravenous preparation in cardiac surgery because its safety profile and reduction in blood loss and frequency of blood transfusion.
There is presently no published randomized controlled trial evaluating blood loss in CABG patients who have received intravenous tranexamic acid, plus topical tranexamic acid or placebo.
- Conditions
- Coronary Artery Disease
- Being tested
- Tranexamic Acid, normal saline
- Keywords
- coronary artery bypass grafting, tranexamic acid, antifibrinolytic, administration, topical, operative blood salvage
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic AcidDrug
Solution containing 2 grams (20mL) tranexamic acid + normal saline (50mL), for a total volume of 70mL poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction.
normal salineDrug
A total volume of 70mL of normal saline poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction. Identical in appearance to the trial drug, and is visually indistinguishable.
| Study group | Role | What they receive |
|---|---|---|
| Trial Drug | Experimental | Solution containing 2 grams tranexamic acid + normal saline Receives: Drug: Tranexamic Acid |
| Placebo | Placebo comparator | Normal saline Receives: Drug: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Volume of Blood Loss From Mediastinal Chest Tubes at Time of Removal (Assuming the Total Volume of Loss is Blood).
According to standard practice, research participants were be transferred to the intensive care unit (ICU) for post-operative monitoring. Measurement of chest tube output began immediately on arrival to the ICU. Hourly measurements were recorded. Data collection ended upon chest tube removal, or return to the operating room for exploratory surgery due to massive blood loss. As per ICU protocol, chest tubes were be removed when blood loss was recorded to be less than 200mL after six consecutive hours.
Measured: From ICU admission post-operatively to mediastinal chest tube removal (placebo group = 20.6 hours; trial group = 19.8 hours)
Number of Units of Packed Red Blood Cells (PRBC) Transfused Following Coronary Artery Bypass Graft Surgery
Research participants were to receive a blood transfusion in the Intensive Care Unit (ICU) post-operatively if hemoglobin reached a nadir of 80g/L, or at the discretion of the intensivist or cardiac surgeon according to patient clinical status. Transfusion was quantified based on the number of units of PRBC received. (1 unit = 1 bag of blood, as prepared by Canadian Blood Services). Clinical status of research participants was followed throughout their duration in the ICU only. Participation in this study ended upon transfer out of the ICU, to the Cardiology Ward.
Measured: From ICU admission to transfer to the Cardiology Ward (placebo group = 24.4 hours; trial group = 24.7 hours)
Secondary outcomes (2)
Volume of Blood Loss at 6 Hours
Volume of chest tube loss at 6 hours (assuming the total volume of loss is blood).
Measured: 6 hours following admission to the Intensive Care Unit
Volume of Blood Loss After 12 Hours
Volume of chest tube loss at 12 hours (assuming the total volume of loss is blood).
Measured: 12 hours following admission to the Intensive Care Unit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study startDec 2011
- Primary completionApr 2012
- Study completionJun 2012
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 (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Saskatchewan
- Sponsor type
- University, hospital or other
- Collaborators
- Saskatoon Health Region
- Responsible party
- Sponsor
- Investigators
- Kelsey Brose, MD, FRCPC, Principal investigator, University of Saskatchewan, Department of Medicine, Division of Hematology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01519245
- Sponsor's protocol ID
- 67452-01
- Status last verified
- May 2013
- First submitted
- 17 Jan 2012
- Last updated
- 2 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Abrishami A, Chung F, Wong J. Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth. 2009 Mar;56(3):202-12. doi: 10.1007/s12630-008-9038-x. Epub 2009 Feb 12.
PubMed 19247741Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006 May;23(5):380-4. doi: 10.1017/S0265021505001894. Epub 2006 Jan 27.
PubMed 16438759Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, Brkic K, Ivkovic M. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg. 2007 Mar;31(3):366-71; discussion 371. doi: 10.1016/j.ejcts.2006.12.003. Epub 2007 Jan 10.
PubMed 17218108De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, Schiavello R, Possati GF. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg. 2000 Mar;119(3):575-80. doi: 10.1016/s0022-5223(00)70139-5.
PubMed 10694619Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L. Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg. 2009 Jun 18;4:25. doi: 10.1186/1749-8090-4-25.
PubMed 19538741
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Application of Tranexamic Acid to Reduce Post-operative Bleeding in Coronary Artery Bypass Surgery
- ClinicalTrials.gov ID
- NCT01519245
- Acronym / sponsor ID
- 67452-01
- Conditions
- Coronary Artery Disease
- Keywords
- coronary artery bypass grafting, tranexamic acid, antifibrinolytic, administration, topical, operative blood salvage
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of SaskatchewanUniversity, hospital or other
- Collaborators
- Saskatoon Health Region
- Study start
- Dec 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 26 Jan 2012 (estimated)
- Results
- Posted 2 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this project is to determine whether the use of tranexamic acid, a clot-promoting drug, applied topically over the heart in coronary artery bypass graft surgery (CABG) will reduce post operative blood loss. The investigators' hypothesis is that the use of a tranexamic acid-containing cardiac bath prior to chest closure will result in a statistically significant reduction in blood loss and transfusion requirements in patients who undergo CABG.
Detailed description
Bleeding is expected during major surgeries. In patients who undergo CABG, the risk for bleeding is increased because of the need for intra-operative anticoagulation, or thinning, of patient blood. This anticoagulation is necessary to reduce the risk of thrombosis potentially precipitated by the cardiopulmonary bypass machine, which pumps blood throughout the body while the surgeon operates on the heart.
Strategies are currently used in the operating room to minimize blood loss and the need for allogenic blood transfusion during and after cardiac surgeries. These strategies include the use of intravenous antifibrinolytic agents, intra-operative red blood cell salvage devices, and topical fibrin sealants. Although the risk of infection from a blood transfusion is very small with modern methods of blood screening, the risk of developing a transfusion reaction is possible and not predictable. Therefore, it is preferred to avoid administering a blood transfusion unless absolutely necessary.
The use of topical antifibrinolytic agents has been explored to further reduce blood loss in cardiac surgery. Several trials have been published in the literature since 1993 evaluating the efficacy of various antifibrinolytic medications applied topically, as a cardiac bath, prior to chest closure in CABG patients to reduce post-operative blood loss and potential need for blood transfusion.
The applicability of the methodology utilized in these studies, however, is limited in the context of the current Canadian practices of cardiac surgery. Considerable differences in the perioperative strategies of these trials are seen, in comparison to current North American practices of cardiac surgery. These trials also compared use of topically applied antifibrinolytic agents, including the lysine analogue tranexamic acid, to a control in the absence of intravenous antifibrinolytic agents. The use of intravenous lysine analogues to reduce peri-operative bleeding has now become a near-standard of care in CABG patients.
Currently, the only available antifibrinolytic agent in Canada is the lysine analogue tranexamic acid. This drug is widely used administered as an intravenous preparation in cardiac surgery because its safety profile and reduction in blood loss and frequency of blood transfusion.
There is presently no published randomized controlled trial evaluating blood loss in CABG patients who have received intravenous tranexamic acid, plus topical tranexamic acid or placebo.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trial Drug | Experimental | Drug: Tranexamic AcidSolution containing 2 grams tranexamic acid + normal saline |
| Placebo | Placebo comparator | Drug: normal salineNormal saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients scheduled for elective or urgent CABG of two to six vessels
Key exclusion criteria (20 listed)
- Hemoglobin of less than 110g/L
- Under 18 years of age
- Body mass less than 75kg
- Presence of an intra-aortic balloon pump
- Emergency surgery, requiring operative intervention within 24 hours of consultation to the cardiac surgery team
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 AcidSolution containing 2 grams (20mL) tranexamic acid + normal saline (50mL), for a total volume of 70mL poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction. | Drug | Trial Drug |
| normal salineA total volume of 70mL of normal saline poured over the heart as a 'cardiac bath' prior to sternotomy closure near the end of surgery. Total duration of immersion is approximately 10 minutes, until mediastinal chest tubes are connected to suction. Identical in appearance to the trial drug, and is visually indistinguishable. | Drug | Placebo |
Primary outcome
Total Volume of Blood Loss From Mediastinal Chest Tubes at Time of Removal (Assuming the Total Volume of Loss is Blood).
Time frame: From ICU admission post-operatively to mediastinal chest tube removal (placebo group = 20.6 hours; trial group = 19.8 hours)
According to standard practice, research participants were be transferred to the intensive care unit (ICU) for post-operative monitoring. Measurement of chest tube output began immediately on arrival to the ICU. Hourly measurements were recorded. Data collection ended upon chest tube removal, or return to the operating room for exploratory surgery due to massive blood loss. As per ICU protocol, chest tubes were be removed when blood loss was recorded to be less than 200mL after six consecutive hours.
Number of Units of Packed Red Blood Cells (PRBC) Transfused Following Coronary Artery Bypass Graft Surgery
Time frame: From ICU admission to transfer to the Cardiology Ward (placebo group = 24.4 hours; trial group = 24.7 hours)
Research participants were to receive a blood transfusion in the Intensive Care Unit (ICU) post-operatively if hemoglobin reached a nadir of 80g/L, or at the discretion of the intensivist or cardiac surgeon according to patient clinical status. Transfusion was quantified based on the number of units of PRBC received. (1 unit = 1 bag of blood, as prepared by Canadian Blood Services). Clinical status of research participants was followed throughout their duration in the ICU only. Participation in this study ended upon transfer out of the ICU, to the Cardiology Ward.
2 secondary outcomes
Volume of Blood Loss at 6 Hours
Time frame: 6 hours following admission to the Intensive Care Unit
Volume of Blood Loss After 12 Hours
Time frame: 12 hours following admission to the Intensive Care Unit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19247741Abrishami A, Chung F, Wong J. Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth. 2009 Mar;56(3):202-12. doi: 10.1007/s12630-008-9038-x. Epub 2009 Feb 12.
- Background: PubMed 16438759Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006 May;23(5):380-4. doi: 10.1017/S0265021505001894. Epub 2006 Jan 27.
- Background: PubMed 17218108Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, Brkic K, Ivkovic M. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg. 2007 Mar;31(3):366-71; discussion 371. doi: 10.1016/j.ejcts.2006.12.003. Epub 2007 Jan 10.
- Background: PubMed 10694619De Bonis M, Cavaliere F, Alessandrini F, Lapenna E, Santarelli F, Moscato U, Schiavello R, Possati GF. Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study. J Thorac Cardiovasc Surg. 2000 Mar;119(3):575-80. doi: 10.1016/s0022-5223(00)70139-5.
- Background: PubMed 19538741Fawzy H, Elmistekawy E, Bonneau D, Latter D, Errett L. Can local application of Tranexamic acid reduce post-coronary bypass surgery blood loss? A randomized controlled trial. J Cardiothorac Surg. 2009 Jun 18;4:25. doi: 10.1186/1749-8090-4-25.
Related trials for Coronary Artery Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
Not yet recruitingPhase 4
Roxadustat and Myocardial Injury After Off-Pump Coronary Artery Bypass Surgery
Coronary Artery Disease, Coronary Artery Bypass Grafting
RecruitingObservational study
Preoperative Gastric Ultrasound and Left Ventricular Function in Coronary Artery Bypass Surgery
Coronary Artery Disease, Left Ventricular Systolic Dysfunction
Active, not recruiting
The OCTOBER Trial - European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction (OCTOBER)
Ischaemic Heart Disease, Ischemic Heart Disease
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.
Kelsey Brose, MD, FRCPC principal investigator
University of Saskatchewan, Department of Medicine, Division of Hematology
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic Acid and normal saline in people with Coronary Artery Disease, run by University of Saskatchewan.
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 1 inclusion and 20 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 2 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Jul 2013). 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?
Total Volume of Blood Loss From Mediastinal Chest Tubes at Time of Removal (Assuming the Total Volume of Loss is Blood). (time frame: From ICU admission post-operatively to mediastinal chest tube removal (placebo group = 20.6 hours; trial group = 19.8 hours)). The study lists 2 primary outcomes in all. 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 NCT01519245, which also lists 5 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 2 Jul 2013.