Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.

Knee Prosthesis Clinical Trial

Official title:

Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02319915
• Other study ID #: CHUB-PTGexacyl-001
• Status: Completed
• Phase: Early Phase 1
• First received: December 15, 2014
• Last updated: January 18, 2018
• Start date: February 18, 2015
• Est. completion date: March 14, 2017

Study information

• Verified date: January 2018
• Source: Brugmann University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the pharmacokinetic profile of tranexamic acid injected intra-articularly with or without adrenaline, in a population of patients undergoing knee replacement.

Description:

Orthopedic population, especially during a knee surgery, is at risk of significant bleeding and blood transfusion in the perioperative period. Tissue damage is associated with the activation of a cascade of mechanisms, in which the activation of the fibrinolyse plays an important role. This is why anti-fibrinolytic agents are regularly used in this context to reduce the perioperative bleeding and the use of blood transfusions.

In the majority of cases, tranexamic acid, an analogue agent of lysine, is administered by an intravenous injection and more recently, by an intra-articular injection.

Several questions however remain unanswered.

• what is the clearance of this substance ?

• does an intra-articular resorbtion exist, resulting in a plasmatic rate of the substance ? If yes, what is the plasmatic rate ?

• Is the intra-articular effect of tranexamic acid predominant compared to its systemic effect ?

• Does the addition of adrenalin increase the effect of the tranexamic acid by acting on its absorption ?

The efficacy, safety and better administration route of the tranexamic acid remain unknown when injected intra-articularly. The goal of this study is to realize the first pharmacokinetic study after an intra-articular injection of tranexamic acid, alone of along with adrenalin, in a knee neo-articulation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 14, 2017
• Est. primary completion date: March 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• programmed PTG, right or left

• surgery planned within the CHU Brugmann Hospital (Dr Reynders)

• ASA I to ASA III

• Signed informed consent within the patient file

Exclusion Criteria:

• re-do surgery

• urgent or multiple surgery

• ASA IV or higher

• Patients with a BMI superior or equal to 40

• Patient is a Jehovah Witness

• Allergy or contra-indication to tranexamic acid

• Coagulation troubles, defined as: Platelet count < 80 000/mm3 and/or PTT <70% and/or aPTT >45s and/or Fibrinogen <100mg/dL

• Preoperatory renal insufficiency defined as Creatinin > 3mg/dL and/or Dialysis patients.

Related Conditions & MeSH terms

• Knee Prosthesis

Intervention

Drug:
• Tranexamic Acid

• Adrenalin

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (8)

Chareancholvanich K, Siriwattanasakul P, Narkbunnam R, Pornrattanamaneewong C. Temporary clamping of drain combined with tranexamic acid reduce blood loss after total knee arthroplasty: a prospective randomized controlled trial. BMC Musculoskelet Disord. 2012 Jul 20;13:124. doi: 10.1186/1471-2474-13-124. — View Citation

Charoencholvanich K, Siriwattanasakul P. Tranexamic acid reduces blood loss and blood transfusion after TKA: a prospective randomized controlled trial. Clin Orthop Relat Res. 2011 Oct;469(10):2874-80. doi: 10.1007/s11999-011-1874-2. Epub 2011 Apr 22. — View Citation

Gandhi R, Evans HM, Mahomed SR, Mahomed NN. Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Res Notes. 2013 May 7;6:184. doi: 10.1186/1756-0500-6-184. — View Citation

Ishida K, Tsumura N, Kitagawa A, Hamamura S, Fukuda K, Dogaki Y, Kubo S, Matsumoto T, Matsushita T, Chin T, Iguchi T, Kurosaka M, Kuroda R. Intra-articular injection of tranexamic acid reduces not only blood loss but also knee joint swelling after total knee arthroplasty. Int Orthop. 2011 Nov;35(11):1639-45. doi: 10.1007/s00264-010-1205-3. Epub 2011 Jan 21. — View Citation

Mutsuzaki H, Ikeda K. Intra-articular injection of tranexamic acid via a drain plus drain-clamping to reduce blood loss in cementless total knee arthroplasty. J Orthop Surg Res. 2012 Sep 29;7:32. doi: 10.1186/1749-799X-7-32. — View Citation

Ortega-Andreu M, Pérez-Chrzanowska H, Figueredo R, Gómez-Barrena E. Blood loss control with two doses of tranexamic Acid in a multimodal protocol for total knee arthroplasty. Open Orthop J. 2011 Mar 16;5:44-8. doi: 10.2174/1874325001105010044. — View Citation

Sa-Ngasoongsong P, Channoom T, Kawinwonggowit V, Woratanarat P, Chanplakorn P, Wibulpolprasert B, Wongsak S, Udomsubpayakul U, Wechmongkolgorn S, Lekpittaya N. Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2-hour clamp drain: a prospective triple-blinded randomized controlled trial. Orthop Rev (Pavia). 2011;3(2):e12. doi: 10.4081/or.2011.e12. Epub 2011 Jun 29. — View Citation

Samama CM, Langeron O, Rosencher N, Capdevila X, Rouche P, Pegoix M, Bernière J, Coriat P. Aprotinin versus placebo in major orthopedic surgery: a randomized, double-blinded, dose-ranging study. Anesth Analg. 2002 Aug;95(2):287-93, table of contents. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The pharmacokinetic profile of tranexamic acid	Blood sampling will be performed to establish the pharmacokinetic profile of tranexamic acid. T0 will be defined as the injection time of tranexamic acid. The first blood sampling (T1) will be made 5 minutes after, with the garrot still in place. The garrot will then be loosened and the following blood samplings will take place at 1 minute, 5 minute, 15 minutes, 30 minutes, 1h, 2h, 4h, 8h, 12h and 24h after garrot loosening. 1ml of blood will be taken at each blood sampling. The blood will be placed in a tube suited for chemistry analysis (green tube with gel) and sent directly to the laboratory for analysis.	24h
Secondary	Knee diameter	This will be part of the semi-quantitative evaluation of the knee bleeding. The diameter of both knees (the one undergoing surgery and the untouched one) will be measured before and after surgery.	12h
Secondary	Net weight of the compresses	This will be part of the semi-quantitative evaluation of the knee bleeding. The net weight of the blood soaked compresses will be measured.	12h
Secondary	Size of the blood stain on the band aid	This will be part of the semi-quantitative evaluation of the knee bleeding. The size of the blood stain, defined as the percentage of the circumference of the band aid that is blood stained, will be measured.	12h
Secondary	Blood loss	The blood loss will be deduced from the estimated circulating volume and the patient hematocrit level before and 72h after surgery.	72h