Post CABG BleedingLATANCT01600599
Reducing Post Operative Bleeding Following Cabg
A study testing Tranexamic Acid and saline in people with Post CABG Bleeding, run by University of Malaya at 1 site in Malaysia.
Trial summary
The purpose of this study is to assess the efficacy of IV Tranexamic Acid and topical Tranexamic Acid to control post op bleeding following Coronary Artery Bypass Graft Surgery using Cardiopulmonary Bypass. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Post CABG Bleeding
- What is being tested?
- Tranexamic Acid and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteMalaysia
- Study dates
- Jan 2011to May 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- primary isolated CABG
Who cannot join
- patients who will have combined procedure
- redo-surgery
- bleeding diathesis (Haemophilia or platelet count ,100 x 109 L1)
- renal impairment (Creatinine > 130umol/L)
- known allergy to TA
- recent (< 7 days before surgery) intake of anti-platelets (eg Aspirin, Clopidogrel, Ticlid) or heparin administration within 48 hours of operation
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
Pusat Perubatan University Malaya
Petaling Jaya, Selangor, 59100
About this study
Official title: Efficacy in Controlling Bleeding Post-coronary Bypass Surgery Using Combination of Local Application of Tranexamic Acid and Intravenous Tranexamic Compared to Intravenous Tranexamic Acid Alone. A Randomized Controlled Trial
The purpose of this study is to assess the efficacy of IV Tranexamic Acid and topical Tranexamic Acid to control post op bleeding following Coronary Artery Bypass Graft Surgery using Cardiopulmonary Bypass.
Read the detailed description
Coagulopathy is a common problem after open heart surgery using cardiopulmonary bypass (CPB). Some bleeding is significant enough to require early re-exploration to control hemorrhage in 2-4% of patients.(1,2) In adults, excessive post-operative bleeding occurs in association with repeat operations, emergency procedures, female gender, small body mass index, older age, peripheral vascular disease, renal insufficiency ( creatinine > 1.8g/dL) , poor nutrition ( albumin < 4g/dL) and in patients who have experienced prolonged CPB durations. (3,4)
Factors that contribute to coagulopathy after coronary artery bypass grafting (CABG) using CPB include thrombocytopenia, acquired platlet dysfunction, loss of clotting factors, free heparin and increased fibrinolysis. (5-7). Lemmer and Colleagues (8) found that extracorporeal circulation results in significant fibrinolysis, as reflected by increased concentrations of plasmin and fibrin degradation products (FDP), both of which have deleterious effects on platlet function. Fibrinolysis was found to be responsible for 25-45% of significant post-bypass bleeding. (9)
Many antifibrinolytic agents have been used to reduce post-bypass bleeding. These include ε- Aminocaproic Acid (10), Aprotinin (11) and Tranexamic Acid (TA) (12).
TA has been found to bind to lysine binding sites of plasmin and plasminogen. Saturation of these sites displaces plasminogen from the fibrin surface thus inhibiting fibrinolysis.(13). TA has been used both systemically and topically.
Due to the natural barrier properties of the pericardium, which prevents the free diffusion of substances, experimental studies have shown that the local application of different medications in to the pericardial cavity can lead to desirable therapeutic effects without significant systemic absorption. (14-16)
There has been a systemic review and meta-analysis study done looking at 8 trials (622 patients) using topical antifibrinolytic agents (aprotinin and tranexamic acid). No adverse effects were reported following usage of topical antifibrinolytics.(17)
Topical TA has also been successfully used in controlling bleeding in bladder, gynaecological, oral, \& oropharyngeal surgeries. (18-20)
There has been no authors thus far who have compared application of intravenous TA to combination of application of intravenous TA and topical TA.
This study is based on a hypothesis that the combination of intravenous (IV) TA and topical TA administration will significantly reduce the amount of post-op bleeding significantly following CABG using CPB.
- Conditions
- Post CABG Bleeding
- Being tested
- Tranexamic Acid, saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic AcidDrug
intravenous 1g and topical 1g
salineDrug
100mls of topical saline
| Study group | Role | What they receive |
|---|---|---|
| IV & topical TA | Active comparator | patients in this group will receive both intravenous \& topical tranexamic acid Receives: Drug: Tranexamic Acid |
| IV tranexamic acid & Topical Saline | Placebo comparator | Not described Receives: Drug: saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
chest drain output
chest drain output (in mls) following post CABG in the 1st hour and total drain output when the drain is removed.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2012 (estimated)
- Study startJan 2011
- Primary completionApr 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Post CABG 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Malaya
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Theevashini Krishnasamy, MBChB, MRCS, University of Malaya
- Investigators
- theevashini krishnasamy, MBChB, MRCS, Principal investigator, University of Malaya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01600599
- Sponsor's protocol ID
- 180880
- Acronym
- LATA
- Status last verified
- May 2012
- First submitted
- 2 May 2012
- Last updated
- 18 May 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Munoz JJ, Birkmeyer NJ, Dacey LJ, Birkmeyer JD, Charlesworth DC, Johnson ER, Lahey SJ, Norotsky M, Quinn RD, Westbrook BM, O'Connor GT. Trends in rates of reexploration for hemorrhage after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg. 1999 Oct;68(4):1321-5. doi: 10.1016/s0003-4975(99)00728-6.
PubMed 10543500Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg. 1996 May;111(5):1037-46. doi: 10.1016/s0022-5223(96)70380-x.
PubMed 8622301Magovern JA, Sakert T, Benckart DH, Burkholder JA, Liebler GA, Magovern GJ Sr, Magovern GJ Jr. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg. 1996 Jan;61(1):27-32. doi: 10.1016/0003-4975(95)00808-X.
PubMed 8561579Despotis GJ, Filos KS, Zoys TN, Hogue CW Jr, Spitznagel E, Lappas DG. Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients. Anesth Analg. 1996 Jan;82(1):13-21. doi: 10.1097/00000539-199601000-00004.
PubMed 8712388Kucuk 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 7508070Kevy SV, Glickman RM, Bernhard WF, Diamond LK, Gross RE. The pathogenesis and control of the hemorrhagic defect in open heart surgery. Surg Gynecol Obstet. 1966 Aug;123(2):313-8. No abstract available.
PubMed 5913482Daily PO, Lamphere JA, Dembitsky WP, Adamson RM, Dans NF. Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study. J Thorac Cardiovasc Surg. 1994 Jul;108(1):99-106; discussion 106-8.
PubMed 8028387Cosgrove DM 3rd, Heric B, Lytle BW, Taylor PC, Novoa R, Golding LA, Stewart RW, McCarthy PM, Loop FD. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Ann Thorac Surg. 1992 Dec;54(6):1031-6; discussion 1036-8. doi: 10.1016/0003-4975(92)90066-d.
PubMed 1280411Longstaff C. Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis. 1994 Aug;5(4):537-42.
PubMed 7531000Baek SH, Hrabie JA, Keefer LK, Hou D, Fineberg N, Rhoades R, March KL. Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric oxide donor reduces luminal narrowing after porcine coronary angioplasty. Circulation. 2002 Jun 11;105(23):2779-84. doi: 10.1161/01.cir.0000017432.19415.3e.
PubMed 12057994Kolettis TM, Kazakos N, Katsouras CS, Niokou D, Pappa L, Koulouras V, Stefanou P, Seferiadis C, Malamou-Mitsi V, Michalis LK, Marselos M, Sideris DA. Intrapericardial drug delivery: pharmacologic properties and long-term safety in swine. Int J Cardiol. 2005 Mar 30;99(3):415-21. doi: 10.1016/j.ijcard.2004.03.004.
PubMed 15771922Waxman S, Pulerwitz TC, Rowe KA, Quist WC, Verrier RL. Preclinical safety testing of percutaneous transatrial access to the normal pericardial space for local cardiac drug delivery and diagnostic sampling. Catheter Cardiovasc Interv. 2000 Apr;49(4):472-7. doi: 10.1002/(sici)1522-726x(200004)49:43.0.co;2-y.
PubMed 10751782
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy in Controlling Bleeding Post-coronary Bypass Surgery Using Combination of Local Application of Tranexamic Acid and Intravenous Tranexamic Compared to Intravenous Tranexamic Acid Alone. A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01600599
- Acronym / sponsor ID
- LATA / 180880
- Conditions
- Post CABG Bleeding
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of MalayaUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 17 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy of IV Tranexamic Acid and topical Tranexamic Acid to control post op bleeding following Coronary Artery Bypass Graft Surgery using Cardiopulmonary Bypass.
Detailed description
Coagulopathy is a common problem after open heart surgery using cardiopulmonary bypass (CPB). Some bleeding is significant enough to require early re-exploration to control hemorrhage in 2-4% of patients.(1,2) In adults, excessive post-operative bleeding occurs in association with repeat operations, emergency procedures, female gender, small body mass index, older age, peripheral vascular disease, renal insufficiency ( creatinine > 1.8g/dL) , poor nutrition ( albumin < 4g/dL) and in patients who have experienced prolonged CPB durations. (3,4)
Factors that contribute to coagulopathy after coronary artery bypass grafting (CABG) using CPB include thrombocytopenia, acquired platlet dysfunction, loss of clotting factors, free heparin and increased fibrinolysis. (5-7). Lemmer and Colleagues (8) found that extracorporeal circulation results in significant fibrinolysis, as reflected by increased concentrations of plasmin and fibrin degradation products (FDP), both of which have deleterious effects on platlet function. Fibrinolysis was found to be responsible for 25-45% of significant post-bypass bleeding. (9)
Many antifibrinolytic agents have been used to reduce post-bypass bleeding. These include ε- Aminocaproic Acid (10), Aprotinin (11) and Tranexamic Acid (TA) (12).
TA has been found to bind to lysine binding sites of plasmin and plasminogen. Saturation of these sites displaces plasminogen from the fibrin surface thus inhibiting fibrinolysis.(13). TA has been used both systemically and topically.
Due to the natural barrier properties of the pericardium, which prevents the free diffusion of substances, experimental studies have shown that the local application of different medications in to the pericardial cavity can lead to desirable therapeutic effects without significant systemic absorption. (14-16)
There has been a systemic review and meta-analysis study done looking at 8 trials (622 patients) using topical antifibrinolytic agents (aprotinin and tranexamic acid). No adverse effects were reported following usage of topical antifibrinolytics.(17)
Topical TA has also been successfully used in controlling bleeding in bladder, gynaecological, oral, \& oropharyngeal surgeries. (18-20)
There has been no authors thus far who have compared application of intravenous TA to combination of application of intravenous TA and topical TA.
This study is based on a hypothesis that the combination of intravenous (IV) TA and topical TA administration will significantly reduce the amount of post-op bleeding significantly following CABG using CPB.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV & topical TA | Active comparator | Drug: Tranexamic Acidpatients in this group will receive both intravenous \& topical tranexamic acid |
| IV tranexamic acid & Topical Saline | Placebo comparator | Drug: saline |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- primary isolated CABG
Key exclusion criteria (6 listed)
- patients who will have combined procedure
- redo-surgery
- bleeding diathesis (Haemophilia or platelet count ,100 x 109 L1)
- renal impairment (Creatinine > 130umol/L)
- known allergy to TA
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 Acidintravenous 1g and topical 1g | Drug | IV & topical TA |
| saline100mls of topical saline | Drug | IV tranexamic acid & Topical Saline |
Primary outcome
chest drain output
Time frame: 4 days
chest drain output (in mls) following post CABG in the 1st hour and total drain output when the drain is removed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2012.
- Background: PubMed 10543500Munoz JJ, Birkmeyer NJ, Dacey LJ, Birkmeyer JD, Charlesworth DC, Johnson ER, Lahey SJ, Norotsky M, Quinn RD, Westbrook BM, O'Connor GT. Trends in rates of reexploration for hemorrhage after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg. 1999 Oct;68(4):1321-5. doi: 10.1016/s0003-4975(99)00728-6.
- Background: PubMed 8622301Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M. Reexploration for bleeding is a risk factor for adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg. 1996 May;111(5):1037-46. doi: 10.1016/s0022-5223(96)70380-x.
- Background: PubMed 8561579Magovern JA, Sakert T, Benckart DH, Burkholder JA, Liebler GA, Magovern GJ Sr, Magovern GJ Jr. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg. 1996 Jan;61(1):27-32. doi: 10.1016/0003-4975(95)00808-X.
- Background: PubMed 8712388Despotis GJ, Filos KS, Zoys TN, Hogue CW Jr, Spitznagel E, Lappas DG. Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients. Anesth Analg. 1996 Jan;82(1):13-21. doi: 10.1097/00000539-199601000-00004.
- 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 5913482Kevy SV, Glickman RM, Bernhard WF, Diamond LK, Gross RE. The pathogenesis and control of the hemorrhagic defect in open heart surgery. Surg Gynecol Obstet. 1966 Aug;123(2):313-8. No abstract available.
- Background: PubMed 8028387Daily PO, Lamphere JA, Dembitsky WP, Adamson RM, Dans NF. Effect of prophylactic epsilon-aminocaproic acid on blood loss and transfusion requirements in patients undergoing first-time coronary artery bypass grafting. A randomized, prospective, double-blind study. J Thorac Cardiovasc Surg. 1994 Jul;108(1):99-106; discussion 106-8.
- Background: PubMed 1280411Cosgrove DM 3rd, Heric B, Lytle BW, Taylor PC, Novoa R, Golding LA, Stewart RW, McCarthy PM, Loop FD. Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. Ann Thorac Surg. 1992 Dec;54(6):1031-6; discussion 1036-8. doi: 10.1016/0003-4975(92)90066-d.
- Background: PubMed 7531000Longstaff C. Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents. Blood Coagul Fibrinolysis. 1994 Aug;5(4):537-42.
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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.
theevashini krishnasamy, MBChB, MRCS principal investigator
University of Malaya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tranexamic Acid and saline in people with Post CABG Bleeding, run by University of Malaya at 1 site in Malaysia.
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 6 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 18 May 2012. 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 Malaysia. 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. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
chest drain output (time frame: 4 days). 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 NCT01600599, which also lists 21 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 18 May 2012.