DEPOSITION: Pilot Study Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery
Sponsors
Source
Population Health Research Institute
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief 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. 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.
Overall Status
Completed
Start Date
2017-12-21
Completion Date
2018-09-04
Primary Completion Date
2018-09-04
Phase
Phase 4
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Median Volume of Mediastinal Fluid Collected From Participants |
Fluid collected in the first 24 hours after the surgical procedure |
Secondary Outcome
Measure |
Time Frame |
|
Number of Participants With Seizures |
Patients will be followed post-operatively until hospital discharge |
|
Number of Participants With Mortality |
Patients will be followed post-operatively until hospital discharge |
|
Number of Participants With RBC Transfusion |
Intra-operative and post-operative RBC transfusions |
|
Number of Participants With Re-operation for Bleeding or Tamponade |
Patients will be followed post-operatively until hospital discharge |
|
Median Number of Hours Participants Spent in ICU |
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 |
on arrival in ICU within 3 hours |
Enrollment
97
Conditions
Intervention
Intervention Type
Drug
Intervention Name
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.
Arm Group Label
TA Topical
TA Intravenous
Other Name
Cyklokapron
Eligibility
Criteria
Inclusion Criteria:
- Male or female >= 18 years old
- Undergoing cardiac surgical procedure with the use of cardiopulmonary bypass and
median sternotomy
- Provide written informed consent
Exclusion Criteria:
- 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 )
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Andre Lamy, MD MHSc |
Principal Investigator |
Population Health Research Institute |
Location
Facility |
|
Hamilton General Hospital Hamilton Ontario L8L 2X2 Canada |
Location Countries
Country
Canada
Verification Date
2019-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Tranexamic Acid
Arm Group
Arm Group Label
TA Topical
Arm Group Type
Active Comparator
Description
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.
Arm Group Label
TA Intravenous
Arm Group Type
Active Comparator
Description
2 syringes of 50ml (5mg) Tranexamic Acid for intravenous injection or placebo.
Firstreceived Results Date
N/A
Reference
Citation
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.
PMID
3766524
Citation
Harker 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.
PMID
6448643
Citation
Despotis 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.
PMID
8283896
Citation
Lemmer 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.
PMID
7508070
Citation
Santos 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. Epub 2005 Dec 15.
PMID
16400465
Citation
Pleym 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):923-8, table of contents.
PMID
12651635
Citation
Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières 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.
PMID
27774838
Citation
Martin 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.
PMID
19020118
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.
PMID
22054656
Acronym
DEPOSITION
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Tranexamic Acid intravenous + Placebo topical versus Placebo intravenous + Tranexamic Acid topical
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
The pharmacy will prepare 1 syringe of 50 ml of topical TA (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. TA 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.
Study First Submitted
November 17, 2017
Study First Submitted Qc
December 12, 2017
Study First Posted
December 18, 2017
Last Update Submitted
September 12, 2019
Last Update Submitted Qc
September 12, 2019
Last Update Posted
September 24, 2019
Results First Submitted
May 28, 2019
Results First Submitted Qc
August 1, 2019
Results First Posted
September 9, 2019
Provided Document Section
Provided Document
Document Type
Study Protocol and Statistical Analysis Plan
Document Has Protocol
Yes
Document Has Icf
No
Document Has Sap
Yes
Document Date
March 16, 2018
Document Url
https://ClinicalTrials.gov/ProvidedDocs/61/NCT03376061/Prot_SAP_000.pdf
ClinicalTrials.gov processed this data on December 10, 2019
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
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Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.