Surgical Blood LossPhase 4NCT00985920
Topical Tranexamic Acid for Total Knee Arthroplasty
A Phase 4 study testing tranexamic acid in people with Surgical Blood Loss and Total Knee Arthroplasty, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Total knee arthroplasty (TKA), the definitive treatment of osteoarthritis, is often associated with excessive postoperative bleeding due to increased fibrinolysis. Hence, the objective of the proposed study is to determine the role of topical application of tranexamic acid (TA), an anti-fibrinolytic agent, into the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Surgical Blood Loss, Total Knee Arthroplasty
- What is being tested?
- tranexamic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2007to Nov 2009
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult patients (greater than 18 years old).
- Patients scheduled for primary unilateral total knee arthroplasty.
Who cannot join
- Allergy to tranexamic acid
- Acquired disturbances of color vision
- Preoperative anemia (hemoglobin <110 in females; hemoglobin <120 in males)
- Refusal of blood products (Jehovah's witnesses),
- Preoperative use of anticoagulant therapy - coumadin, heparin within 5 days of surgery, fibrinolytic disorders requiring intraoperative antifibrinolytic treatment,
- Coagulopathy (preoperative platelet count < 150,000/mm3, INR >1.4, prolonged PTT (>1.4 x normal))
Show all 16Show fewer
- A previous history of thromboembolic disease (e.g. CVA, DVT or PE)
- Pregnancy
- Breastfeeding
- Significant co-morbidities:
- severe ischemic heart disease; NYHA Class III, IV,
- previous myocardial infarction
- severe pulmonary disease, e.g. FEV1<50% normal,
- plasma creatinine greater than 115 µmol/l in males and more than 100 µmol/l in females
- hepatic failure
- Intraoperative surgical/medical/anesthetic complications occur, e.g. MI, intraoperative bone fracture or neurovascular injury
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Intraoperative Topical Application of Tranexamic Acid in Reducing Perioperative Bleeding in Total Knee Arthroplasty
Total knee arthroplasty (TKA), the definitive treatment of osteoarthritis, is often associated with excessive postoperative bleeding due to increased fibrinolysis. Hence, the objective of the proposed study is to determine the role of topical application of tranexamic acid (TA), an anti-fibrinolytic agent, into the knee joint just before closure during TKA to reduce perioperative bleeding. The investigators' hypothesis is that in patients undergoing unilateral primary TKA, intraoperative application of 1.5 g or 3.0g topical TA into the knee joint before closure reduces perioperative bleeding as depicted by a decrement in the maximal drop in hemoglobin concentration following surgery. This proposal describes a randomized, double-blinded, placebo-controlled clinical trial with three arms. The primary outcome is the extent of the postoperative reduction in hemoglobin levels. Secondary outcomes will include transfusion requirements, hospital stay, joint functionality, quality of life and safety of using topical TA. Topical application of TA is a novel intraoperative approach that has not been used or studied in TKA. However if it is effective, it will directly reduce postoperative intra-articular bleeding without subsequent systemic absorption and thromboembolism. In addition, the reduction in microvascular intra-articular bleeding will lead to less pain and infection rates as well as improved surgical functional outcomes.
Read the detailed description
Three million (1 in 10) Canadians suffer from Osteoarthritis (OA). Total knee arthroplasty (TKA), i.e. knee replacement surgery is the definitive treatment for knee osteoarthritis which alleviates pain and restores physical functioning. However, it can be associated with excessive postoperative bleeding leading to increased mortality and morbidity. The current blood conservation techniques, i.e. preoperative erythropoietin and autologous blood donation, do not reduce bleeding from the surgical site. As a result, many patients require blood transfusion with the associated risks and costs. In TKA, postoperative bleeding is attributed to diffuse microvascular bleeding as a result of increased fibrinolytic activity caused by releasing of the tourniquet which is routinely applied to provide appropriate surgical exposure during surgery. Therefore, tranexamic acid (TA), an antifibrinolytic agent which blocks the dissolution of hemostatic fibrin, can decrease blood loss following TKA. The systemic administration of TA, however, carries the risk of thromboembolic events such as deep vein thrombosis (DVT) or pulmonary embolism (PE). In TKA, this is of greater importance, as the patients are at higher risk of thromboembolic events. Topical application of TA in the surgical field is a cost-effective and simple route of administration that has been shown to reduce bleeding in dental, cardiac, and spine surgeries while minimizing systemic absorption and thromboembolism. Another major advantage of this approach is to prevent diffuse microvascular bleeding at the site of raw tissue surfaces resulting in decreased infection rate, pain, and increased range of motion (ROM) of the knee joints. In spite of these potential benefits, the innovative idea of topical application of TA has not been studied in TKA. However, if it is shown to be efficacious in decreasing postoperative bleeding, it can be incorporated into routine clinical practice with immediate beneficial impacts on patient care and quality of life.
Hypothesis:
In patients undergoing unilateral primary/revision TKA, intraoperative application of 1.5 g or 3 g topical TA into the surgical wound for five minutes before closure reduces perioperative bleeding as depicted by the maximal drop in systemic hemoglobin concentration during the postoperative period.
General Objective:
To study the role of tranexamic acid as a therapeutic tool, applied intraoperatively into the surgical wound, to reduce perioperative blood loss in patients undergoing a unilateral primary/revision TKA.
Specific Objectives:
To determine:
- the efficacy of topical application of TA to reduce perioperative transfusion requirements.
- the safety of topical application of TA (complications such as DVT).
- the systemic absorption of TA after topical application into the surgical wound.
- the impact of postoperative hemoglobin (Hb) reduction on patients' quality of life.
- the impact of topical application of TA on the length of hospital stay.
- the impact of topical application of TA on ROM, pain, and surgical infection rate of the knee joint.
- the incidence of autologous and allogenic blood transfusion in patients receiving the standard.
- multimodal blood conservation techniques for TKA surgery at our institution
- to compare the efficacy and safety of high dose (3 g) of TA versus low dose (1.5 g) of TA.
- Conditions
- Surgical Blood Loss, Total Knee Arthroplasty
- Being tested
- tranexamic acid, Placebo
- Keywords
- blood loss, postoperative
- Medical subject headings
- Blood Loss, Surgical, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tranexamic acidDrug
Also called cyklokapron
Patients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo).
The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues.
PlaceboDrug
Also called normal saline
Patients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo).
The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues.
| Study group | Role | What they receive |
|---|---|---|
| Tranexamic acid, 1.5 g | Experimental | 1.5 g of tranexamic acid in 50 cc of normal saline solution is given to the patients. Receives: Drug: tranexamic acid |
| Tranexamic acid, 3.0 g | Experimental | 3.0 g of tranexamic acid in 50 cc of normal saline is given to the patients. Receives: Drug: tranexamic acid |
| Placebo, saline | Placebo comparator | 50 cc of sterile normal saline solution is given to the patients. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calculated blood loss
Measured: Postoperative day 1-3
Secondary outcomes (7)
Total prevalence of drug-related adverse events
Measured: one month after the medication/placebo administration
perioperative packed red blood cell transfusion requirements
Measured: Intraoperative and postoperative day 1-3
Systemic absorption of TA after topical application into the surgical wound
Measured: 1 hr after the surgey (after touniquet release)
length of hospital stay
Measured: postoperative
The change in the knee joint range of motion at flexion
Measured: Postoperative day 2
The amount of pain at the knee joint measured by a visual scale (VAS)
Measured: Postoperative week 6
Health-related quality of life determined by the Western Ontario and Mac Master Universities Osteoarthritis (WOMAC) index score
Measured: Postoperative week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2009 (estimated)
- Study startSep 2007
- Primary completionOct 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Surgical Blood LossStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Investigators
- Jean Wong, MD, FRCPC, Principal investigator, Staff Anesthesiologist , Assistant Professor, Department of Anesthesia, Toronto Western Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00985920
- Sponsor's protocol ID
- 070199A
- Status last verified
- Apr 2011
- First submitted
- 28 Sep 2009
- Last updated
- 11 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intraoperative Topical Application of Tranexamic Acid in Reducing Perioperative Bleeding in Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT00985920
- Acronym / sponsor ID
- 070199A
- Conditions
- Surgical Blood Loss, Total Knee Arthroplasty
- Keywords
- blood loss, postoperative
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- Sep 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 29 Sep 2009 (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.
Total knee arthroplasty (TKA), the definitive treatment of osteoarthritis, is often associated with excessive postoperative bleeding due to increased fibrinolysis. Hence, the objective of the proposed study is to determine the role of topical application of tranexamic acid (TA), an anti-fibrinolytic agent, into the knee joint just before closure during TKA to reduce perioperative bleeding. The investigators' hypothesis is that in patients undergoing unilateral primary TKA, intraoperative application of 1.5 g or 3.0g topical TA into the knee joint before closure reduces perioperative bleeding as depicted by a decrement in the maximal drop in hemoglobin concentration following surgery. This proposal describes a randomized, double-blinded, placebo-controlled clinical trial with three arms. The primary outcome is the extent of the postoperative reduction in hemoglobin levels. Secondary outcomes will include transfusion requirements, hospital stay, joint functionality, quality of life and safety of using topical TA. Topical application of TA is a novel intraoperative approach that has not been used or studied in TKA. However if it is effective, it will directly reduce postoperative intra-articular bleeding without subsequent systemic absorption and thromboembolism. In addition, the reduction in microvascular intra-articular bleeding will lead to less pain and infection rates as well as improved surgical functional outcomes.
Detailed description
Three million (1 in 10) Canadians suffer from Osteoarthritis (OA). Total knee arthroplasty (TKA), i.e. knee replacement surgery is the definitive treatment for knee osteoarthritis which alleviates pain and restores physical functioning. However, it can be associated with excessive postoperative bleeding leading to increased mortality and morbidity. The current blood conservation techniques, i.e. preoperative erythropoietin and autologous blood donation, do not reduce bleeding from the surgical site. As a result, many patients require blood transfusion with the associated risks and costs. In TKA, postoperative bleeding is attributed to diffuse microvascular bleeding as a result of increased fibrinolytic activity caused by releasing of the tourniquet which is routinely applied to provide appropriate surgical exposure during surgery. Therefore, tranexamic acid (TA), an antifibrinolytic agent which blocks the dissolution of hemostatic fibrin, can decrease blood loss following TKA. The systemic administration of TA, however, carries the risk of thromboembolic events such as deep vein thrombosis (DVT) or pulmonary embolism (PE). In TKA, this is of greater importance, as the patients are at higher risk of thromboembolic events. Topical application of TA in the surgical field is a cost-effective and simple route of administration that has been shown to reduce bleeding in dental, cardiac, and spine surgeries while minimizing systemic absorption and thromboembolism. Another major advantage of this approach is to prevent diffuse microvascular bleeding at the site of raw tissue surfaces resulting in decreased infection rate, pain, and increased range of motion (ROM) of the knee joints. In spite of these potential benefits, the innovative idea of topical application of TA has not been studied in TKA. However, if it is shown to be efficacious in decreasing postoperative bleeding, it can be incorporated into routine clinical practice with immediate beneficial impacts on patient care and quality of life.
Hypothesis:
In patients undergoing unilateral primary/revision TKA, intraoperative application of 1.5 g or 3 g topical TA into the surgical wound for five minutes before closure reduces perioperative bleeding as depicted by the maximal drop in systemic hemoglobin concentration during the postoperative period.
General Objective:
To study the role of tranexamic acid as a therapeutic tool, applied intraoperatively into the surgical wound, to reduce perioperative blood loss in patients undergoing a unilateral primary/revision TKA.
Specific Objectives:
To determine:
- the efficacy of topical application of TA to reduce perioperative transfusion requirements.
- the safety of topical application of TA (complications such as DVT).
- the systemic absorption of TA after topical application into the surgical wound.
- the impact of postoperative hemoglobin (Hb) reduction on patients' quality of life.
- the impact of topical application of TA on the length of hospital stay.
- the impact of topical application of TA on ROM, pain, and surgical infection rate of the knee joint.
- the incidence of autologous and allogenic blood transfusion in patients receiving the standard.
- multimodal blood conservation techniques for TKA surgery at our institution
- to compare the efficacy and safety of high dose (3 g) of TA versus low dose (1.5 g) of TA.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tranexamic acid, 1.5 g | Experimental | Drug: tranexamic acid1.5 g of tranexamic acid in 50 cc of normal saline solution is given to the patients. |
| Tranexamic acid, 3.0 g | Experimental | Drug: tranexamic acid3.0 g of tranexamic acid in 50 cc of normal saline is given to the patients. |
| Placebo, saline | Placebo comparator | Drug: Placebo50 cc of sterile normal saline solution is given to the patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All adult patients (greater than 18 years old).
- Patients scheduled for primary unilateral total knee arthroplasty.
Key exclusion criteria (16 listed)
- Allergy to tranexamic acid
- Acquired disturbances of color vision
- Preoperative anemia (hemoglobin <110 in females; hemoglobin <120 in males)
- Refusal of blood products (Jehovah's witnesses),
- Preoperative use of anticoagulant therapy - coumadin, heparin within 5 days of surgery, fibrinolytic disorders requiring intraoperative antifibrinolytic treatment,
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: cyklokapronPatients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo). The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues. | Drug | Tranexamic acid, 1.5 g, Tranexamic acid, 3.0 g |
| PlaceboAlso: normal salinePatients will receive a solution containing either 1.5g or 3 g of tranexamic acid in 50 ml of normal saline (0.9% sodium chloride) or only 50 ml of saline without TA (placebo). The treatment solution will be prepared under sterile conditions and coded at TWH pharmacy. In the OR the sterile bag containing the solution will be given to the scrub nurse. The contents (50 ml) will be emptied in a sterile surgical bowl. TA or placebo solution (50 ml) will be then applied to the open joint and tissues by the bulb syringe and will be left in contact with the tissues for 5 minutes. Excess solution will be subsequently suctioned by placing the suction tip on the cemented component without touching the joint and surrounding tissues. | Drug | Placebo, saline |
Primary outcome
Calculated blood loss
Time frame: Postoperative day 1-3
7 secondary outcomes
Total prevalence of drug-related adverse events
Time frame: one month after the medication/placebo administration
perioperative packed red blood cell transfusion requirements
Time frame: Intraoperative and postoperative day 1-3
Systemic absorption of TA after topical application into the surgical wound
Time frame: 1 hr after the surgey (after touniquet release)
length of hospital stay
Time frame: postoperative
The change in the knee joint range of motion at flexion
Time frame: Postoperative day 2
The amount of pain at the knee joint measured by a visual scale (VAS)
Time frame: Postoperative week 6
Health-related quality of life determined by the Western Ontario and Mac Master Universities Osteoarthritis (WOMAC) index score
Time frame: Postoperative week 6
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 11 Apr 2011.
Related trials for Surgical Blood Loss
Enrolling by invitation
Early Outcome of Simultaneous Bilateral Total Knee Replacement With and Without Tourniquet
Arthroplasty, Replacement, Knee, Blood Loss, Surgical
Recruiting
Hemocoll, Avitene, or Bone Wax for Cancellous Bone Bleeding After Single-Ray Amputation
Hemostasis, Surgical Blood Loss
Active, not recruitingObservational study
Safe and Timely Antithrombotic Removal (STAR) Registry
Hemorrhage, Surgical, Hemorrhage Postoperative
RecruitingPhase 3
Phase 3 Trial of Reltodecacog Alfa (VMX-C001) vs Usual Pharmacological Care in Patients Taking a FXa Direct Oral Anticoagulant Who Require Urgent Surgery With or Without Heparin.
Blood Loss, Surgical, Coagulation Disorder
Not yet recruitingPhase 3
Tranexamic Acid to Reduce Blood Loss After Varus Derotation Osteotomy
Cerebral Palsy, Hip Surgery Corrective
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.
Jean Wong, MD, FRCPC principal investigator
Staff Anesthesiologist , Assistant Professor, Department of Anesthesia, Toronto Western Hospital
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 Surgical Blood Loss and Total Knee Arthroplasty, run by University Health Network, Toronto 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 2 inclusion and 16 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 Apr 2011. 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. 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 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?
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?
Calculated blood loss (time frame: Postoperative day 1-3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Apr 2011.