Clinical Study Assessing Idrabiotaparinux Sodium Injections Once-weekly in Pulmonary Embolism Therapeutic Approach (CASSIOPEA)

An International, Multicenter, Randomized, Double-blind, Double-dummy, Parallel Group, Study of 3-month or 6-month Treatment With SSR126517E (3.0 mg s.c. Once-weekly) Versus Oral INR-adjusted Warfarin in the Treatment of Patients With Symptomatic Pulmonary Embolism With or Without Symptomatic Deep Venous Thrombosis

Objectives are to evaluate whether idrabiotaparinux sodium (SSR126517E) is as least as effective as a standard warfarin treatment to prevent recurrence of venous thromboembolic events (VTE) in patients with symptomatic pulmonary embolism (PE) with or without symptomatic deep venous thrombosis (DVT) and to assess its safety (bleedings) versus warfarin.

Study Overview

• Status: Completed
• Conditions: Embolism; Thrombosis
• Intervention / Treatment: Drug: Idrabiotaparinux sodium; Drug: Avidin; Drug: Placebo (for warfarin); Drug: Enoxaparin; Drug: Warfarin; Drug: Placebo (for idrabiotaparinux sodium)

Detailed Description

Treatment with a therapeutic dose of any low molecular weight heparin (LMWH) or unfractioned heparin (UFH) or fondaparinux is allowed only within the 36 hours immediately preceding randomization. Randomization is performed as soon as the diagnosis of PE (and DVT if concomitant suspected symptomatic DVT) is confirmed.

Allocation to treatment is done centrally by Interactive Voice Response System (IVRS) and stratified by (1) center, (2) intended treatment duration, ie, 3 months or 6 months. At randomization, the planned duration of treatment (3 or 6 months) is prespecified by the Investigator and determined on the assessment of risk of VTE recurrence. Participants are randomized to either idrabiotaparinux + placebo of warfarin, or warfarin + placebo of idrabiotaparinux, with an initial treatment of at least 5 days with enoxaparin in both treatment groups.

Participants in the 3-month stratum have an additional 13-week observational period after cessation of study treatment. Participants in the 6-month stratum have a 13-week up to 26-week observational period.

• Study Type: Interventional
• Enrollment (Actual): 3202
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Sanofi-Aventis Administrative Office
• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia
      • sanofi-aventis Australia & New Zealand administrative office
• Austria
  • Wien, Austria
    • Sanofi-Aventis Administrative Office
• Belarus
  • Minsk, Belarus
    • Sanofi-Aventis Administrative Office
• Belgium
  • Diegem, Belgium
    • Sanofi-Aventis Administrative Office
• Brazil
  • Sao Paulo, Brazil
    • Sanofi-Aventis Administrative Office
• Bulgaria
  • Sofia, Bulgaria
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Chile
  • Santiago, Chile
    • Sanofi-Aventis Administrative Office
• China
  • Shangai, China
    • Sanofi-Aventis Administrative Office
• Colombia
  • Santafe de Bogota, Colombia
    • Sanofi-Aventis Administrative Office
• Croatia
  • Zagreb, Croatia
    • Sanofi-Aventis Administrative Office
• Czech Republic
  • Praha, Czech Republic
    • Sanofi-Aventis Administrative Office
• Denmark
  • Horsholm, Denmark
    • Sanofi-Aventis Administrative Office
• Egypt
  • Cairo, Egypt
    • Sanofi-Aventis Administrative Office
• Estonia
  • Tallinn, Estonia
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Greece
  • Athens, Greece
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Israel
  • Natanya, Israel
    • Sanofi-Aventis Administrative Office
• Italy
  • Milano, Italy
    • Sanofi-Aventis Administrative Office
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Norway
  • Lysaker, Norway
    • Sanofi-Aventis Administrative Office
• Peru
  • Lima, Peru
    • Sanofi-Aventis Administrative Office
• Philippines
  • Makati City, Philippines
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Puerto Rico
  • Puerto Rico, Puerto Rico
    • Sanofi-Aventis Administraive Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Admnistrative Office
• Slovakia
  • Brastislava, Slovakia
    • Sanofi-Aventis Administrative Office
• South Africa
  • Midrand, South Africa
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• Sweden
  • Bromma, Sweden
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• Ukraine
  • Kiev, Ukraine
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic pulmonary embolism with or without symptomatic deep vein thrombosis

Exclusion Criteria:

• End stage renal failure, hepatic failure, uncontrolled hypertension;
• Active bleeding or high risk for bleeding;
• Pregnancy or childbearing potential without proper contraceptive measures, threatened abortion.
• Breastfeeding.
• Known allergy to idraparinux or idrabiotaparinux, avidin or egg proteins;
• hypersensitivity to warfarin, enoxaparin, heparin or pork product; or any other contraindication listed in the labelling of warfarin or enoxaparin;
• Indication of prolonged anticoagulation therapy for other reason than PE;
• Life expectancy < 6 months;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idrabiotaparinux; Idrabiotaparinux sodium, 3.0 mg, once-weekly for 3 or 6 months depending on the stratum, after enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).	Drug: Idrabiotaparinux sodium; 0.5 mL pre-filled syringe for 3.0 mg Subcutaneous injection; Other Names: Biotinylated Idraparinux; SSR126517; Drug: Avidin; 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes; Other Names: SSR29261; Drug: Placebo (for warfarin); Warfarin matching capsules Oral administration; Drug: Enoxaparin; Prefilled syringes as locally registered Subcutaneous injection
Active Comparator: Warfarin; Warfarin, INR-adjusted dose, started 24 hours after the start of enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days, and continued for 3 or 6 months depending on the stratum. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).	Drug: Avidin; 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes; Other Names: SSR29261; Drug: Enoxaparin; Prefilled syringes as locally registered Subcutaneous injection; Drug: Warfarin; Capsules with 1 or 5 mg for INR-adjusted dose (INR checked at least once a month) Oral administration; Drug: Placebo (for idrabiotaparinux sodium); 0.5 mL pre-filled syringe Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC)	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC)	6 months
Incidence of any clinically relevant bleeding as classified by the CIAC (ie, major bleeding and other clinically relevant non major bleeding)	3 months, 6 months and 3- to 6-month post-treatment follow-up

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Buller HR, Gallus AS, Pillion G, Prins MH, Raskob GE; Cassiopea Investigators. Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial. Lancet. 2012 Jan 14;379(9811):123-9. doi: 10.1016/S0140-6736(11)61505-5. Epub 2011 Nov 28.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: June 27, 2006
• First Submitted That Met QC Criteria: June 27, 2006
• First Posted (Estimate): June 28, 2006

Study Record Updates

• Last Update Posted (Estimate): March 21, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Deep venous thrombosis; pulmonary embolism; anticoagulant drugs
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Micronutrients; Vitamins; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Vitamin B Complex; Enoxaparin; Warfarin; Biotin; Idraparinux; Idrabiotaparinux
• Other Study ID Numbers: EFC6034; EudraCT:2006-001786-42