Clinical trial NCT00793234: Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery
Official title: Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery: A Dose-Escalating, Multicenter, Randomised, Active- Controlled Open Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Total Knee Replacement Surgery
Keywords: TKR
VTE
DVT
Lead sponsor: ThromboGenics
Sponsor class: INDUSTRY
Collaborators: name: BioInvent International AB
name: Covance
First posted: 2008-11-19
Enrollment: 316
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: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and efficacy of a single administration of TB-402 for the prevention of VTE in patients undergoing knee replacement surgery.

Detailed description: Currently available anticoagulant therapies for the prevention of VTE include low molecular weight heparins, pentasaccharides and vitamin K antagonists, all of which have inherent limitations(1-3).

Improved anticoagulant agents are therefore required(4). A novel antithrombotic agent requires demonstration of both efficacy and safety in relevant populations. Phase II studies are frequently performed in patients undergoing total hip replacement and/or total knee replacement because of the high and well documented incidence of deep vein thrombosis in the absence of adequate thromboprophylaxis(5-7).

In this study, we assess the safety and efficacy of TB-402, a novel antithrombotic agent that partially inhibits factor VIII, in the prevention of VTE in patients undergoing total knee replacement surgery.

Eligibility criteria: Inclusion Criteria:

* Male or female patients aged \> 18 and \< 80 years old
* Female patients should be post menopausal
* Patients undergoing primary elective total knee replacement surgery
* Written informed consent obtained from the patient (or a legally acceptable representative) prior to inclusion in the study
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

* Body weight \< 50 kg or \> 100 kg
* Patients undergoing a hemiarthroplasty, surface repair or revisionary surgery of the knee
* Confirmed symptomatic deep vein thrombosis or pulmonary embolism within the past year
* Anticipated use of indwelling intrathecal or epidural catheter for more than 4 h after surgery or during the entire study
* Uncontrolled hypertension (SBP\>160 mm Hg or DBP \> 100 mm Hg)
* History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year

Primary outcomes:
measure: The occurrence of total bleeding defined as major and/or clinically relevant non-major bleeding events, from randomisation until the end of the study.
timeFrame: All visists from randomization to end of study
measure: Composite of the occurrence of asymptomatic DVT as detected by bilateral venography and symptomatic VTE, i.e. DVT or fatal or non-fatal PE.
timeFrame: Prior to hospital discharge Day 7-11
Secondary outcomes:
measure: Incidence of major bleeding events
timeFrame: All visists from randomization to end of study
measure: Incidence of clinically significant non-major bleeding events
timeFrame: All visits from randomization to end of study
measure: Incidence of minor bleeding events
timeFrame: All visits from randomization to end of study
measure: Incidence of all cause mortality
timeFrame: All visits from randomization to end of study
measure: Incidence of adverse events
timeFrame: All visists from randomization to end of study
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: SHAT of orthopedics, traumatology and surgery "Sv. Pantaleimon " - Pleven Department of Orthopaedics and Traumatology
city: Plovdiv
country: Bulgaria
facility: Dept. of Orthopedics, UMHAT "Saint George"
city: Rousse
country: Bulgaria
facility: MHAT Rousse
city: Sofia
country: Bulgaria
facility: MHAT "Sveta Anna" AD - Sofia, Clinic of Orthopedics and Traumatology
city: Varna
country: Bulgaria
facility: MHAT "Sv. Anna", Department of Orthopaedics and Traumatology
city: Beer - Sheva
country: Israel
facility: Soroka MC
city: Beer-Yaakov
country: Israel
facility: Asaf Harofeh MC
city: Haifa
country: Israel
facility: Rambam MC
city: Jerusalem
country: Israel
facility: Shaare Zedek MC
city: Kfar Saba
country: Israel
facility: Meir Medical Center (MC)
city: Petach Tikva
country: Israel
facility: Beilinson Hospital
city: Rehovot
country: Israel
facility: Kaplan MC
city: Tel Aviv
country: Israel
facility: Sourasky MC
city: Liepāja
country: Latvia
facility: Ltd "Liepajas regionala slimnica"
city: Riga
country: Latvia
facility: Ltd "Traumatologijas un ortopedijas slimnica"
city: Valmiera
country: Latvia
facility: Vidzemes slimnica
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy Klinika Ortopedii i Traumatologii Narządu Ruchu
city: Kraków
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. L. Rydygiera w Krakowie, Oddział Kliniczny Ortopedii i Traumatologii Narządu Ruchu
city: Lubuskie
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie, Katedra i Klinika Ortopedii Traumatologii i Rehabilitacji
city: Podlaski
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku, Klinika Ortopedii i Traumatologii
city: Warszawa
country: Poland
facility: Wojewódzki Szpital Bródnowski Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Chirurgii Urazowo-Ortopedycznej i Rehabilitacji
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Urgenta Sf. Ioan Bucuresti
city: Cluj - Napoca
country: Romania
facility: Spitalul Clinic de Urgenta Prof. Dr. Octavian Fodor CLUJ NAPOCA
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Craiova
city: Cheliabinsk
country: Russian Federation
facility: Municipal Healthcare Institution "City Clinical Hospital No. 3"
city: Moscow
country: Russian Federation
facility: Moscow State Healthcare Institution "City Clinical Hospital No. 15 n.a. O.M. Filatov"
city: Orenburg
country: Russian Federation
facility: Municipal Healthcare Institution "City Clinical Hospital No. 4"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Medical Institution: Clinical Hospital #122 named after L.G. Sokolov under the Federal Medical-Biological Agency
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Healthcare Institution "Municipal Multi-Speciality Hospital No. 2"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Institution "Russian Research Institute of Traumatology and Orthopedics n.a. R.R. Vreden under the Federal Authority for Healthcare and Social Development"
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg State Healthcare Institution "Aleksandrovskaya Hospital"
city: Samara
country: Russian Federation
facility: State Healthcare Institution "Samara Regional Clinical Hospital n.a. M.I. Kalinin"
city: Cherkassy
country: Ukraine
facility: Cherkasska Regional Hospital. Department of Orthopedics and Traumatology.
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankіvsk Regional Clinical Hospital, Department of ortopedics and traumatology.
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital, Department of Orthopedics and Traumatology
Study officials:
References: