Serum Concentration of Tranexamic Acid After Topical Administration in Massive Weight Loss Skin Reducing Surgery

Study Overview
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Brief Summary
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Tranexamic acid is a drug that prevents clotted blood from dissolving and hence reduces bleeding. It is routinely given intravenously in many surgical situations where there is a risk of major bleeding. Concerns regarding possible adverse effects from intravenous use prevents a more widespread use, even in smaller surgeries. Topical application - using the drug directly on the wound surface- may give a higher concentration at the site of bleeding but a lower concentration in the rest of the body, and hence a lower risk of adverse effects. Here it will be investigated to what extent a defined dose of the drug is absorbed systemically - into the blood stream - when it is applied topically. This will then be compared to the concentration in the blood stream when administered intravenously. Blood samples will be obtained at defined time intervals after administration from patients receiving topical and patients receiving intravenous administration of the same single dose of tranexamic acid. Will less of the drug enter the blood stream if it is applied directly to the wound?

Official Title
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Serum Concentration of Tranexamic Acid After Topical Administration in Massive Weight Loss Skin Reducing Surgery

Conditions
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Surgical Wound, Bleeding

Intervention / Treatment
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* Drug: Tranexamic Acid 25 mg/ml for wound surface moistening
* Drug: Tranexamic Acid 5 mg/ml as bolus in wound cavity
* Drug: Tranexamic Acid Injectable Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: planned for major skin reduction surgery (abdominoplasty/panniculectomy) after massive weight loss, or planned for orthopaedic hip replacement surgery Exclusion Criteria: pregnancy breastfeeding known allergy to tranexamic acid/Cyklokapron® ongoing or former thromboembolic event known kidney failure, as defined by estimated glomerular filtration rate (eGFR)<60 ml/min

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 12 participants will be included in each of 3 groups: wound moistening group (skin reduction surgery), wound bolus group (after skin reduction surgery), and (for comparison) a group getting usual intravenous tranexamic acid before orthopedic surgery. It is not possible to conduct a formal power calculation, as it is completely unknown which concentrations could be expected after topical use; however, these concentrations are expected to be considerably lower than after intravenous use. Consequently, it is expected that the AUC values in all subjects in the topical (skin reducing surgery) group are far lower than in all subjects in the intravenous (orthopaedic surgery) group. 12 subjects is therefor considered an appropriate number.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: abdominoplasty moistening<br>Tranexamic Acid 25 mg/ml for wound surface moistening prior to wound closure | Drug: Tranexamic Acid 25 mg/ml for wound surface moistening<br>* Wound surface moistened with 20 ml of tranexamic acid 25 mg/ml (total dose 500 mg) prior to wound closure<br>* Other names: Cyclokapron;|
| Experimental: abdominoplasty bolus<br>Tranexamic Acid 5 mg/ml as bolus in wound cavity after wound closure | Drug: Tranexamic Acid 5 mg/ml as bolus in wound cavity<br>* 200 ml of tranexamic acid 5 mg/ml (total dose 1 g) as a bolus instilled into the wound cavity after wound closure, which will remain in the cavity until the activation of drains one hour later<br>* Other names: Cyclokapron;|
| Active Comparator: preoperative intravenous administration<br>Tranexamic Acid Injectable Solution administered before hip replacement surgery | Drug: Tranexamic Acid Injectable Solution<br>* 1 g of tranexamic acid administered intravenously in accordance with prevailing routines directly prior to planned surgical procedure.<br>* Other names: Cyclokapron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of tranexamic acid | as described by the Area Under the (time-concentration) Curve (AUC) from 0 to infinity, alternatively from 0 to 240 minutes if drug levels after 24 hours do not allow for such extrapolation | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from 0 to 240 min | if AUC from 0 to infinity turns out to be the primary end point. | 24 hours | 
| Maximum concentration (Cmax) | Maximal level of serum tranexamic acid in measurements | 24 hours | 
| Timepoint for maximum serum concentration (Tmax) | Timepoint for serum tranexamic acid read from AUC | 24 hours | 
| Elimination half-life | Reading elimination half-life from AUC | 24 hours | 
| Adverse events | Possible adverse reactions or other complaints observed or reported by the patient - telephone interview | four weeks | 
| Adverse events | Possible adverse reactions or complaints observed or reported on the first postoperative day - clinical observation | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemostasis, Surgical, Tranexamic Acid, Antifibrinolytic Agents, Administration, Cutaneous, Administration, Intravenous, Administration, Topical