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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00345618

Collaborator

(none)

3,202

Enrollment

Locations

Arms

Duration (Months)

84.3

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Embolism Thrombosis	Drug: Idrabiotaparinux sodium Drug: Warfarin Drug: Placebo (for idrabiotaparinux sodium) Drug: Avidin Drug: Placebo (for warfarin) Drug: Enoxaparin	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

3202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

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: 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 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

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: 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

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

Outcome Measures

Primary Outcome Measures

Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC) [3 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis Administrative Office	Buenos Aires		Argentina
3	sanofi-aventis Australia & New Zealand administrative office	Macquarie Park	New South Wales	Australia
4	Sanofi-Aventis Administrative Office	Wien		Austria
5	Sanofi-Aventis Administrative Office	Minsk		Belarus
6	Sanofi-Aventis Administrative Office	Diegem		Belgium
7	Sanofi-Aventis Administrative Office	Sao Paulo		Brazil
8	Sanofi-Aventis Administrative Office	Sofia		Bulgaria
9	Sanofi-Aventis Administrative Office	Laval		Canada
10	Sanofi-Aventis Administrative Office	Santiago		Chile
11	Sanofi-Aventis Administrative Office	Shangai		China
12	Sanofi-Aventis Administrative Office	Santafe de Bogota		Colombia
13	Sanofi-Aventis Administrative Office	Zagreb		Croatia
14	Sanofi-Aventis Administrative Office	Praha		Czech Republic
15	Sanofi-Aventis Administrative Office	Horsholm		Denmark
16	Sanofi-Aventis Administrative Office	Cairo		Egypt
17	Sanofi-Aventis Administrative Office	Tallinn		Estonia
18	Sanofi-Aventis Administrative Office	Paris		France
19	Sanofi-Aventis Administrative Office	Athens		Greece
20	Sanofi-Aventis Administrative Office	Mumbai		India
21	Sanofi-Aventis Administrative Office	Natanya		Israel
22	Sanofi-Aventis Administrative Office	Milano		Italy
23	Sanofi-Aventis Administrative Office	Mexico		Mexico
24	Sanofi-Aventis Administrative Office	Gouda		Netherlands
25	Sanofi-Aventis Administrative Office	Lysaker		Norway
26	Sanofi-Aventis Administrative Office	Lima		Peru
27	Sanofi-Aventis Administrative Office	Makati City		Philippines
28	Sanofi-Aventis Administrative Office	Warszawa		Poland
29	Sanofi-Aventis Administrative Office	Porto Salvo		Portugal
30	Sanofi-Aventis Administraive Office	Puerto Rico		Puerto Rico
31	Sanofi-Aventis Admnistrative Office	Moscow		Russian Federation
32	Sanofi-Aventis Administrative Office	Brastislava		Slovakia
33	Sanofi-Aventis Administrative Office	Midrand		South Africa
34	Sanofi-Aventis Administrative Office	Barcelona		Spain
35	Sanofi-Aventis Administrative Office	Bromma		Sweden
36	Sanofi-Aventis Administrative Office	Istanbul		Turkey
37	Sanofi-Aventis Administrative Office	Kiev		Ukraine
38	Sanofi-Aventis Administrative Office	Guildford Surrey		United Kingdom