Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery - Full Text View

Purpose

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.

Condition	Intervention	Phase
Total Knee Replacement Surgery	Drug: TB-402 Drug: Enoxaparin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Knee Replacement

Drug Information available for: Enoxaparin sodium

U.S. FDA Resources

Further study details as provided by ThromboGenics:

Primary Outcome Measures:

The occurrence of total bleeding defined as major and/or clinically relevant non-major bleeding events, from randomisation until the end of the study. [ Time Frame: All visists from randomization to end of study ] [ Designated as safety issue: Yes ]
Composite of the occurrence of asymptomatic DVT as detected by bilateral venography and symptomatic VTE, i.e. DVT or fatal or non-fatal PE. [ Time Frame: Prior to hospital discharge Day 7-11 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of major bleeding events [ Time Frame: All visists from randomization to end of study ] [ Designated as safety issue: Yes ]
Incidence of clinically significant non-major bleeding events [ Time Frame: All visits from randomization to end of study ] [ Designated as safety issue: Yes ]
Incidence of minor bleeding events [ Time Frame: All visits from randomization to end of study ] [ Designated as safety issue: Yes ]
Incidence of all cause mortality [ Time Frame: All visits from randomization to end of study ] [ Designated as safety issue: Yes ]
Incidence of adverse events [ Time Frame: All visists from randomization to end of study ] [ Designated as safety issue: Yes ]

Enrollment:	316
Study Start Date:	December 2008
Study Completion Date:	March 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 0.3 mg/kg TB-402	Drug: TB-402 TB-402 administered as single bolus 18-24 post total knee replacement surgery.
Experimental: 2 0.6 mg/kg TB-402	Drug: TB-402 TB-402 administered as single bolus 18-24 post total knee replacement surgery.
Experimental: 3 1.2 mg/kg TB-402	Drug: TB-402 TB-402 administered as single bolus 18-24 post total knee replacement surgery.
Active Comparator: 4	Drug: Enoxaparin Enoxaparin 40mg/day sc injection for at least 10 days post-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

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793234

Locations

Bulgaria
SHAT of orthopedics, traumatology and surgery "Sv. Pantaleimon " - Pleven Department of Orthopaedics and Traumatology
Pleven, Bulgaria, 5800
Dept. of Orthopedics, UMHAT "Saint George"
Plovdiv, Bulgaria, 4002
MHAT Rousse
Rousse, Bulgaria, 7002
MHAT "Sveta Anna" AD - Sofia, Clinic of Orthopedics and Traumatology
Sofia, Bulgaria, 1709
MHAT "Sv. Anna", Department of Orthopaedics and Traumatology
Varna, Bulgaria, 9000
Israel
Soroka MC
Beer - Sheva, Israel, 84101
Asaf Harofeh MC
Beer-Yaakov, Israel, 70300
Rambam MC
Haifa, Israel, 31096
Shaare Zedek MC
Jerusalem, Israel, 91031
Meir Medical Center (MC)
Kfar Saba, Israel, 44281
Beilinson Hospital
Petach Tikva, Israel, 49100
Kaplan MC
Rehovot, Israel, 76100
Sourasky MC
Tel Aviv, Israel, 64239
Latvia
Ltd "Liepajas regionala slimnica"
Liepāja, Latvia, LV-3400
Ltd "Traumatologijas un ortopedijas slimnica"
Riga, Latvia, LV-1005
Vidzemes slimnica
Valmiera, Latvia, LV 4201
Poland
Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy Klinika Ortopedii i Traumatologii Narządu Ruchu
Bydgoszcz, Poland, 85-094
Wojewódzki Szpital Specjalistyczny im. L. Rydygiera w Krakowie, Oddział Kliniczny Ortopedii i Traumatologii Narządu Ruchu
Kraków, Poland, 31-826
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie, Katedra i Klinika Ortopedii Traumatologii i Rehabilitacji
Lubuskie, Poland, 20-090
Uniwersytecki Szpital Kliniczny w Białymstoku, Klinika Ortopedii i Traumatologii
Podlaski, Poland, 15-276
Wojewódzki Szpital Bródnowski Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Chirurgii Urazowo-Ortopedycznej i Rehabilitacji
Warszawa, Poland, 03-242
Romania
Spitalul Clinic de Urgenta Sf. Ioan Bucuresti
Bucuresti, Romania, 042122
Spitalul Clinic de Urgenta Prof. Dr. Octavian Fodor CLUJ NAPOCA
Cluj - Napoca, Romania, 400132
Spitalul Clinic Judetean de Urgenta Craiova
Craiova, Romania, 200642
Russian Federation
Municipal Healthcare Institution "City Clinical Hospital No. 3"
Cheliabinsk, Russian Federation, 454136
Moscow State Healthcare Institution "City Clinical Hospital No. 15 n.a. O.M. Filatov"
Moscow, Russian Federation, 111539
Municipal Healthcare Institution "City Clinical Hospital No. 4"
Orenburg, Russian Federation, 460000
Saint Petersburg State Healthcare Institution "Municipal Multi-Speciality Hospital No. 2"
Saint Petersburg, Russian Federation, 194354
Federal State Medical Institution: Clinical Hospital #122 named after L.G. Sokolov under the Federal Medical-Biological Agency
Saint Petersburg, Russian Federation, 194291
Federal State Institution "Russian Research Institute of Traumatology and Orthopedics n.a. R.R. Vreden under the Federal Authority for Healthcare and Social Development"
Saint Petersburg, Russian Federation, 197046
Saint Petersburg State Healthcare Institution "Aleksandrovskaya Hospital"
Saint-Petersburg, Russian Federation, 193312
State Healthcare Institution "Samara Regional Clinical Hospital n.a. M.I. Kalinin"
Samara, Russian Federation, 443095
Ukraine
Cherkasska Regional Hospital. Department of Orthopedics and Traumatology.
Cherkassy, Ukraine, 18009
Ivano-Frankіvsk Regional Clinical Hospital, Department of ortopedics and traumatology.
Ivano-Frankivsk, Ukraine, 76008
Odessa Regional Clinical Hospital, Department of Orthopedics and Traumatology
Odessa, Ukraine, 65025

Sponsors and Collaborators

ThromboGenics

BioInvent International AB

Covance

More Information

No publications provided

Responsible Party:	Sophie Gunn/ Clinical Project Manager, ThromboGenics
ClinicalTrials.gov Identifier:	NCT00793234 History of Changes
Other Study ID Numbers:	TB-402-004
Study First Received:	November 18, 2008
Last Updated:	February 8, 2011
Health Authority:	Russia: Pharmacological Committee, Ministry of Health Latvia: State Agency of Medicines Israel: Ministry of Health Romania: Ministry of Public Health Bulgaria: Ministry of Health Poland: Ministry of Health

Keywords provided by ThromboGenics:

TKR
VTE
DVT

Additional relevant MeSH terms:

Thromboembolism
Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Enoxaparin
Anticoagulants

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 16, 2013