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

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

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.

Study Overview

• Status: Completed
• Conditions: Total Knee Replacement Surgery
• Intervention / Treatment: Drug: TB-402; Drug: Enoxaparin

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.

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 4	Drug: Enoxaparin; Enoxaparin 40mg/day sc injection for at least 10 days post-surgery
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The occurrence of total bleeding defined as major and/or clinically relevant non-major bleeding events, from randomisation until the end of the study.	All visists from randomization to end of study
Composite of the occurrence of asymptomatic DVT as detected by bilateral venography and symptomatic VTE, i.e. DVT or fatal or non-fatal PE.	Prior to hospital discharge Day 7-11

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of major bleeding events	All visists from randomization to end of study
Incidence of clinically significant non-major bleeding events	All visits from randomization to end of study
Incidence of minor bleeding events	All visits from randomization to end of study
Incidence of all cause mortality	All visits from randomization to end of study
Incidence of adverse events	All visists from randomization to end of study

Collaborators and Investigators

• Sponsor: ThromboGenics
• Collaborators: Covance; BioInvent International AB

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: November 18, 2008
• First Submitted That Met QC Criteria: November 18, 2008
• First Posted (Estimate): November 19, 2008

Study Record Updates

• Last Update Posted (Estimate): April 7, 2014
• Last Update Submitted That Met QC Criteria: April 4, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: DVT; VTE; TKR
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: TB-402-004