Efficacy of Bemiparin Versus Enoxaparin in the Treatment of DVT

A Multinational, Multicentre, Randomized, Open, Parallel Group Study on the Efficacy and Safety of Bemiparin Sodium (LMWH) Compared to Enoxaparin Sodium (LMWH) in the Treatment of Acute Deep Vein Thrombosis (DVT)

Deep-vein thrombosis (DVT) is a common but under-diagnosed medical condition that occurs when a thrombus forms in one of the large veins, usually in the lower limbs, leading to either partial or complete blocked circulation. The condition may progress to severe health complications, such as pulmonary embolism (PE), if not diagnosed and treated in a timely and effective manner.

The goal of the therapy for lower-extremity DVT is to prevent the extension of thrombus and pulmonary embolism in the short term and to prevent recurrent events in the long-term. Although anticoagulant therapy decreases the risk of recurrent thrombosis, the treatment also increases the risk for major hemorrhage.

This trial aims to optimize the current medical knowledge on the effectiveness and safety of two low molecular weight heparins, bemiparin and enoxaparin in the treatment of deep vein thrombosis.

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis
• Intervention / Treatment: Drug: Enoxaparin sodium; Drug: Bemiparin sodium

Detailed Description

The aim of this study is to demonstrate the therapeutic non-inferiority of bemiparin sodium (LMWH) versus enoxaparin sodium (LMWH) during a 7±2 days treatment period and a follow up of 11 weeks observation period.

Primary endpoint:

The percentage of patients with an improvement in thrombotic burden at Visit 3 (Day 83) defined as a ≥4-point reduction in thrombus score (or at least halving the thrombus score, when the total score is ≤ 6), without confirmed symptomatic extension of recurrence of DVT, confirmed symptomatic PE, or VTE-related death at Visit 3 (Day 83 / Month 3), as measured by complete compression ultrasound (cCUS) by Duplex sonography according to a standardized protocol.

Secondary endpoint:

The secondary efficacy endpoints are defined as the:

• Incidence of symptomatic venous thromboembolic events (VTE) at Visit 3 (Day 83:

• Recurrent DVT
• Pulmonary embolism

Incusion criteria:

Patients with acute deep-vein thrombosis of the leg (DVT) with symptoms of less than 14 days, confirmed by complete compression ultrasound (cCUS) within 48 hours prior study start.

Patients who have given their signed declaration of consent and data protection declaration Males and females aged 18 years

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 3

Contacts and Locations

Study Locations

• Georgia
  • Batumi, Georgia, 6000
    • Unimed Ajara LLC
  • Tbilisi, Georgia, 0112
    • Angiology and Vascular Surgery Academic Clinic
  • Tbilisi, Georgia, 0159
    • Bokhua Clinic of Angiology and Heart Diseases
  • Tbilisi, Georgia, 0159
    • G. Chapidze Emergency Cardiology Centre
  • Tbilisi, Georgia, 0177
    • Aversi Clinic
• Russian Federation
  • Barnaul, Russian Federation
    • Regional State Budget Institution of Healthcare "Regional Clinical Hospital"
  • Irkutsk, Russian Federation, 664079
    • Federal State Budgetary Institution "Scientific Center of Reconstructive and Restorative Surgery" under Siberian Branch of the Russian Academy of Medical Sciences on the clinical base of State Institution of Healthcare, Irkutsk Regional Clinical Hospital
  • Kazan, Russian Federation, 420097
    • State Healthcare Institution "Republican Clinical hospital of the ministry of Health of Republic Tatarstan
  • Moscow, Russian Federation, 117049
    • State Budget Public Health Institution of Moscow "City Clinical Hospital # 1 n.a. N.I. Pirogov"
  • Moscow, Russian Federation, 127299
    • Federal Government Healthcare Institution "Hospital of the Russian Federation Internal Affairs Ministry in Moscow"
  • Moscow, Russian Federation, 305035
    • Federally Funded State Institution "Institute of Surgery n.a. A.V. Vishnevskiy of the Ministry of Healthcare of Russian Federation"
  • Novosibirsk, Russian Federation, 630051
    • State-Financed Healthcare Institution of the Novosibirsk Region "City Clinical Hospital # 2"
  • Omsk, Russian Federation, 664111
    • State Budgetary Institution of the Omsk Region "Regional Clinical Hospital"
  • Perm, Russian Federation, 614107
    • State Independent Healthcare Institution of the Perm kray "City Clinical Hospital # 4"
  • Rostov-on-Don, Russian Federation, 344022
    • State Budget Institution of Hifger Professional Education "Rostov State Medical University" of the Ministry of the Russian Federation
  • Ryazan, Russian Federation, 117997
    • State Budgetary Institution of the Ryazan Region "Regional Clinical Cardiologic Dispensary"
  • Saint-Petersburg, Russian Federation, 192242
    • State Budget Institution "St.Petersburg Janelidze Research Institute of Emergency Medicine"
  • Saint-Petersburg, Russian Federation, 194354
    • St. Petersburg State Public Health Institution "City Multi-field Hospital #2"
  • Saint-Petersburg, Russian Federation, 195271
    • Nongovernmental Public Health Institution " Road Clinical Hospital" of Russian Railways
  • Saint-Petersburg, Russian Federation, 195427
    • State Educational Institution of Additional Professional Education "St.Petersburg Medical Academy of Postgraduate Education of Federal Agency for Health Care and Social Development", Chair of cardiovascular surgery
  • Saint-Petersburg, Russian Federation, 196247
    • St. Petersburg State Public Health Institution "City Hospital #26"
  • Saint-Petersburg, Russian Federation, 197374
    • Federal State Budgetary Institution "Russian Center of Emergency and Radiation Medicine n.a. A.M. Nikiforov" of the Ministry of Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters
  • Samara, Russian Federation, 443099
    • State budgetary institution of higher professional education "Samara State Medical University"
  • Yaroslavl, Russian Federation, 150023
    • State Budget Public Health Institution of Yaroslavl region "Clinical hospital #10", Municipal Clinical Public Health Institution " Medical Unit of Novo-Yaroslavl Petroleum Refinery"
  • Yaroslavl, Russian Federation, 150062
    • State Budget Public Health Institution of Yaroslavl Region "Regional Clinical Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with acute deep-vein thrombosis of the leg (DVT) with symptoms of less than 14 days confirmed by complete compression ultrasound (cCUS) within 48 h prior study starting .
2. Males and females aged ≥18 years
3. Patients who have given their written informed consent.

Exclusion Criteria:

Specific

1. History and presence of familial bleeding diathesis, presence of active bleeding contraindicating anticoagulant therapy, as well as presence of clinically relevant coagulation - and clotting factor disorder,and thrombocytopenia
2. Patients having undergone thrombectomy, having had insertion of a caval filter or who were treated with a fibrinolytic agent to treat the current episode of DVT
3. Treatment with heparin (fractionated or unfractionated), fondaparinux or vitamin K antagonist or warfarin for treatment of DVT for more than 48 h prior to enrolment
4. Long-term treatment with vitamin K antagonists, i.e. for atrial fibrillation, myocardial infarction or cardiomyopathy
5. Isolated distal calf vein thrombosis
6. Isolated superficial vein thrombosis
7. Any other symptomatic venous thromboembolism beside of DVT
8. Known hypersensitivity to heparin (including other pig-derived substances), to the study medications and heparin-derivatives including other LMWHs, warfarin and/or to the active ingredient or any excipient of the study medications
9. Concurrent treatment with platelet function inhibitors (such as acetylsalicylic acid, ticlopidine, clopidogrel, NSAID), fibrinolytic agents and other anticoagulant agents, Glycoprotein IIb/IIIa receptor- antagonists, nitro-glycerine iv, systemic glucocorticoids, penicillin in high doses, dextran, ascorbic acid, digitalis, tetracycline, medical products that could increase the potassium plasma level
10. History of documented or suspected heparin-induced thrombocytopenia (HIT I and II) or platelet count less than 100,000 platelets per mm3
11. Ischaemic stroke one month prior to enrolment
12. History of or active intracranial disorder (cerebral vascular aneurysm, arterio-venous malformation or cerebral neoplasm), history of haemorrhagic stroke or other intracranial bleeding 6 months prior to enrolment, active haemorrhage or increased risk of bleeding due to impaired haemostatics or organ lesion (e.g. peptic ulcer, hepatic failure, haemorrhagic stroke, macroscopic visible urogenital bleeding, cerebral vascular aneurysm or cerebral neoplasm) 1 month prior to enrolment.
13. Uncontrolled arterial hypertension: systolic blood pressure > 200 mmHg and diastolic blood pressure > 105 mmHg.
14. Severe impairment of pancreas function, history of gastro-duodenal ulcer disease, nephrolithiasis and/or ureterolithiasis, choroid and retinal vascular disease, suspected vascular retinopathy, vitreous haemorrhage or other intraocular bleedings, or any organic lesion with an increased risk of bleeding.
15. Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, hepatic cirrhosis, hepatic encephalopathy) or liver enzymes (ALT and/or AST) > 5x ULN.

and others

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Enoxaparin sodium; subcutaneous for 7±2 days and starting on Day 2 additionally the oral anticoagulant warfarin	Drug: Enoxaparin sodium; subcutaneous for 7±2 days; Other Names: LMWH; CAS 73334-07-3
Experimental: Bemiprin sodium; Bemiparin sodium (LMWH) s.c. for 7±2 days and starting on Day 2 additionally the oral anticoagulant warfarin	Drug: Bemiparin sodium; subcutaneous application daily for 7±2 days; Other Names: LMWH; CAS 874-98-4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with an improvement in thrombotic burden at Visit 3	83±7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of symptomatic venous thromboembolic events (VTE)	83±7 days

Other Outcome Measures

Outcome Measure	Time Frame
Treatment emergent adverse events (TEAEs)	83±7 days

Collaborators and Investigators

• Sponsor: Berlin-Chemie AG Menarini Group
• Investigators: Study Chair: Maria Th Kaltwasser, Dr., Berlin-Chemie AG

Publications and helpful links

General Publications

• Suchkov IA, Martinez-Gonzalez J, Schellong SM, Garbade T, Falciani M; Bemiparin DVT Study Group. Comparison of Once-Daily Bemiparin with Twice-Daily Enoxaparin for Acute Deep Vein Thrombosis: A Multicenter, Open-Label, Randomized Controlled Trial. Clin Drug Investig. 2018 Feb;38(2):181-189. doi: 10.1007/s40261-017-0600-6.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: June 14, 2013
• First Submitted That Met QC Criteria: June 14, 2013
• First Posted (Estimate): June 18, 2013

Study Record Updates

• Last Update Posted (Estimate): February 4, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Treatment; Deep vein thrombosis; Low molecular weight heparin; Enoxaparin; Bemiparin; DVT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin; Bemiparin; Enoxaparin sodium
• Other Study ID Numbers: Bemiparin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided