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

Total Knee Replacement Surgery Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00793234
• Other study ID #: TB-402-004
• Status: Completed
• Phase: Phase 2
• First received: November 18, 2008
• Last updated: April 4, 2014
• Start date: December 2008
• Est. completion date: March 2010

Study information

• Verified date: April 2014
• Source: ThromboGenics
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Pharmacological Committee, Ministry of HealthLatvia: State Agency of MedicinesIsrael: Ministry of HealthRomania: Ministry of Public HealthBulgaria: Ministry of HealthPoland: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 316
• Est. completion date: March 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Thromboembolism
• Total Knee Replacement Surgery

Intervention

Drug:
• TB-402
TB-402 administered as single bolus 18-24 post total knee replacement surgery.
• Enoxaparin
Enoxaparin 40mg/day sc injection for at least 10 days post-surgery

Locations

Country	Name	City	State
Bulgaria	SHAT of orthopedics, traumatology and surgery "Sv. Pantaleimon " - Pleven Department of Orthopaedics and Traumatology	Pleven
Bulgaria	Dept. of Orthopedics, UMHAT "Saint George"	Plovdiv
Bulgaria	MHAT Rousse	Rousse
Bulgaria	MHAT "Sveta Anna" AD - Sofia, Clinic of Orthopedics and Traumatology	Sofia
Bulgaria	MHAT "Sv. Anna", Department of Orthopaedics and Traumatology	Varna
Israel	Soroka MC	Beer - Sheva
Israel	Asaf Harofeh MC	Beer-Yaakov
Israel	Rambam MC	Haifa
Israel	Shaare Zedek MC	Jerusalem
Israel	Meir Medical Center (MC)	Kfar Saba
Israel	Beilinson Hospital	Petach Tikva
Israel	Kaplan MC	Rehovot
Israel	Sourasky MC	Tel Aviv
Latvia	Ltd "Liepajas regionala slimnica"	Liepaja
Latvia	Ltd "Traumatologijas un ortopedijas slimnica"	Riga
Latvia	Vidzemes slimnica	Valmiera
Poland	Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy Klinika Ortopedii i Traumatologii Narzadu Ruchu	Bydgoszcz
Poland	Wojewódzki Szpital Specjalistyczny im. L. Rydygiera w Krakowie, Oddzial Kliniczny Ortopedii i Traumatologii Narzadu Ruchu	Kraków
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie, Katedra i Klinika Ortopedii Traumatologii i Rehabilitacji	Lubuskie
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Ortopedii i Traumatologii	Podlaski
Poland	Wojewódzki Szpital Bródnowski Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Oddzial Chirurgii Urazowo-Ortopedycznej i Rehabilitacji	Warszawa
Romania	Spitalul Clinic de Urgenta Sf. Ioan Bucuresti	Bucuresti
Romania	Spitalul Clinic de Urgenta Prof. Dr. Octavian Fodor CLUJ NAPOCA	Cluj - Napoca
Romania	Spitalul Clinic Judetean de Urgenta Craiova	Craiova
Russian Federation	Municipal Healthcare Institution "City Clinical Hospital No. 3"	Cheliabinsk
Russian Federation	Moscow State Healthcare Institution "City Clinical Hospital No. 15 n.a. O.M. Filatov"	Moscow
Russian Federation	Municipal Healthcare Institution "City Clinical Hospital No. 4"	Orenburg
Russian Federation	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	Federal State Medical Institution: Clinical Hospital #122 named after L.G. Sokolov under the Federal Medical-Biological Agency	Saint Petersburg
Russian Federation	Saint Petersburg State Healthcare Institution "Municipal Multi-Speciality Hospital No. 2"	Saint Petersburg
Russian Federation	Saint Petersburg State Healthcare Institution "Aleksandrovskaya Hospital"	Saint-Petersburg
Russian Federation	State Healthcare Institution "Samara Regional Clinical Hospital n.a. M.I. Kalinin"	Samara
Ukraine	Cherkasska Regional Hospital. Department of Orthopedics and Traumatology.	Cherkassy
Ukraine	Ivano-Frank?vsk Regional Clinical Hospital, Department of ortopedics and traumatology.	Ivano-Frankivsk
Ukraine	Odessa Regional Clinical Hospital, Department of Orthopedics and Traumatology	Odessa

Sponsors (3)

Lead Sponsor	Collaborator
ThromboGenics	BioInvent International AB, Covance

Countries where clinical trial is conducted

Bulgaria,  Israel,  Latvia,  Poland,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	No
Secondary	Incidence of major bleeding events		All visists from randomization to end of study	Yes
Secondary	Incidence of clinically significant non-major bleeding events		All visits from randomization to end of study	Yes
Secondary	Incidence of minor bleeding events		All visits from randomization to end of study	Yes
Secondary	Incidence of all cause mortality		All visits from randomization to end of study	Yes
Secondary	Incidence of adverse events		All visists from randomization to end of study	Yes