Safety and Efficacy of TeaRx Xa Factor Direct Inhibitor Versus Enoxaparin as a Venous Thromboembolic Events (VTE) Prevention Following Total Knee Replacement

A Multicenter, Randomized, Pilot, Dose-Ranging Clinical Study to Evaluate Safety and Efficacy of TeaRx Xa Factor Direct Inhibitor Versus Enoxaparin as a Venous Thromboembolic Events (VTE) Prevention Following Total Knee Replacement

To evaluate influence of therapy on the following efficacy and safety parameters in different TeaRx dose groups and Enoxaparin group:

• Total venous thromboembolic events (VTE), which includes confirmed deep venous thrombosis (DVT), nonfatal pulmonary embolism (PE), and total mortality
• Incidence of DVT (total, proximal, distal)
• Incidence of nonfatal PE
• Incidence of symptomatic VTE (DVT, PE)
• VTE caused mortality
• Non-VTE caused mortality
• Incidence of all hemorrhagic complications
• Incidence of major and clinically relevant non-major bleeding
• Adverse events (AEs) and serious adverse events (SAEs) from subject complaints, physical examination, vital signs, laboratory results

Study Overview

• Status: Completed
• Conditions: Total Knee Replacement
• Intervention / Treatment: Drug: Enoxaparin; Drug: TeaRx

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation, 420064
    • SHAI "Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan"
  • Moscow, Russian Federation, 105203
    • Federal State Institution "National Medical and Surgical Center n. a. N. I. Pirogov" of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 119435
    • SBEI HPE First Moscow State Medical University n.a. I.M. Sechenov Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 125284
    • SHI of the city of Moscow City Clinical Hospital n.a. S.P. Botkin
  • Nizhny Novgorod, Russian Federation, 603155
    • FSBI "Nizhny Novgorod Research Institute of Traumatology and Orthopedics" of the Ministry of Health of the Russian Federation
  • Orenburg, Russian Federation, 460000
    • SBHI "City Clinical Hospital № 4" of the city of Orenburg
  • Saint Petersburg, Russian Federation, 194354
    • St. Petersburg State Institution of Health "City Hospital № 2"
  • Yaroslavl, Russian Federation, 150003
    • SHI of the Yaroslavl Region Emergency care hospital n. a. N. V. Solovyov

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female, age ≥ 18 years;
• Planned total knee replacement surgery;
• Signed informed consent form;
• Willing to comply with the protocol;
• Willing to use adequate contraception during the trial.

Exclusion Criteria:

• Surgery for acute fracture 4 weeks before screening; history of septic inflammation in the joint; prosthesis revision or one leg missing
• History of venous thrombosis of any location or PE
• History of heparin induced thrombocytopenia or other thrombocytopathy; hemorrhagic diathesis
• History of evident coagulopathy or in a relative
• Congenital thrombophilia
• Bleeding within 6 months of screening; increased risk of bleeding
• BMI less than 18,5 or more than 40 kg/m2
• Systolic BP > 180 mmHg and/or diastolic BP > 110 mmHg registered twice within 15-30 minutes
• Hb ≤ 10.5 g/dL in female or ≤ 11.5 g/dL in male
• Platelets < 100 000/mm3
• Clinical significant abnormalities of APTT and/or INR
• GFR < 30 ml/min/1.73 m2
• ALT or AST ≥ 2 x ULN or total bilirubin ≥1,5 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TeaRx 50 mg; TeaRx: 50 mg per day PO (active 25 mg + placebo 50 mg every 12 hours) during 12 days (±2 days)	Drug: TeaRx; Other Names: TeaRxaban
Experimental: TeaRx 100 mg; TeaRx: 100 mg per day PO (placebo 25 mg + active 50 mg every 12 hours) during 12 days (±2 days)	Drug: TeaRx; Other Names: TeaRxaban
Experimental: TeaRx 150 mg; TeaRx: 150 mg per day PO (active 25 mg + active 50 mg every 12 hours) during 12 days (±2 days)	Drug: TeaRx; Other Names: TeaRxaban
Active Comparator: Enoxaparin; Enoxaparin 40 mg subcutaneous per day (24 hours interval) during 12 days (±2 days)	Drug: Enoxaparin; Other Names: Clexane ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of deep venous thrombosis (DVT) (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement
Incidence of nonfatal pulmonary embolism (PE) (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement
Incidence of symptomatic venous thromboembolic events (DVT, PE) (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement
venous thromboembolic events (VTE) caused mortality (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement
Non-VTE caused mortality (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement
AEs and SAEs from subject complaints, physical examination, vital signs, laboratory results (efficacy of the selected TeaRx dose)	6 weeks following total knee replacement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of bleeding (safety of selected TeaRx dose)	major and clinically relevant non-major bleeding	6 weeks following total knee replacement

Collaborators and Investigators

• Sponsor: TeaRx LLC
• Investigators: Study Chair: Mikhail N. Zamyatin, Prof., Federal State Institution "National Medical and Surgical Center n. a. N. I. Pirogov" of the Ministry of Health of the Russian Federation

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 26, 2017
• First Submitted That Met QC Criteria: March 18, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: March 18, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• 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: CV-TRX-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No