Clinical trial NCT02319915: Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.
Official title: Evaluation of the Pharmacokinetic Profile of Tranexamic Acid, After Injection in a Knee Neo-articulation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Knee Prosthesis
Keywords: tranexamic acid
knee prosthesis
pharmacokinetic profile
Lead sponsor: Brugmann University Hospital
Sponsor class: OTHER
First posted: 2014-12-18
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The pharmacokinetic profile of tranexamic acid
timeFrame: 24h
Secondary outcomes:
measure: Knee diameter
timeFrame: 12h
measure: Net weight of the compresses
timeFrame: 12h
measure: Size of the blood stain on the band aid
timeFrame: 12h
measure: Blood loss
timeFrame: 72h
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Brugmann
Study officials:
affiliation: CHU Brugmann
name: Philippe Van der Linden, MD, Pr
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
citation: Ortega-Andreu M, Perez-Chrzanowska H, Figueredo R, Gomez-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.
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.
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.
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.
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.
citation: Samama CM, Langeron O, Rosencher N, Capdevila X, Rouche P, Pegoix M, Berniere 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. doi: 10.1097/00000539-200208000-00005.