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

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?

Study Overview

• Status: Completed
• Conditions: Bleeding; Surgical Wound
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway
    • St Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: abdominoplasty moistening; Tranexamic Acid 25 mg/ml for wound surface moistening prior to wound closure	Drug: Tranexamic Acid 25 mg/ml for wound surface moistening; Wound surface moistened with 20 ml of tranexamic acid 25 mg/ml (total dose 500 mg) prior to wound closure; Other Names: Cyclokapron
Experimental: abdominoplasty bolus; Tranexamic Acid 5 mg/ml as bolus in wound cavity after wound closure	Drug: Tranexamic Acid 5 mg/ml as bolus in wound cavity; 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; Other Names: Cyclokapron
Active Comparator: preoperative intravenous administration; Tranexamic Acid Injectable Solution administered before hip replacement surgery	Drug: Tranexamic Acid Injectable Solution; 1 g of tranexamic acid administered intravenously in accordance with prevailing routines directly prior to planned surgical procedure.; Other Names: Cyclokapron

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Aleris Helse
• Investigators: Study Director: Birger Henning Endreseth, MD PhD, St Olavs University Hospital

Publications and helpful links

General Publications

• Ausen K, Pleym H, Liu J, Hegstad S, Nordgard HB, Pavlovic I, Spigset O. Serum Concentrations and Pharmacokinetics of Tranexamic Acid after Two Means of Topical Administration in Massive Weight Loss Skin-Reducing Surgery. Plast Reconstr Surg. 2019 Jun;143(6):1169e-1178e. doi: 10.1097/PRS.0000000000005620.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Tranexamic Acid; Administration, Topical; Antifibrinolytic Agents; Administration, Intravenous; Hemostasis, Surgical; Administration, Cutaneous
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Weight; Body Weight Changes; Weight Loss; Surgical Wound; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 270778; 2016-004246-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No