Clinical trial NCT00311090: Bioequipotency Study of Idrabiotaparinux and Idraparinux in Patients With Deep Venous Thrombosis of the Lower Limbs
Official title: International, Multicenter, Randomized, Parallel Group, Double-blind Study, in Patients With Acute Symptomatic Deep Vein Thrombosis of the Lower Limbs, Demonstrating the Bioequipotency at Steady State of Equimolar Doses of SSR126517E (3.0 mg) Once a Week and SR34006 (2.5 mg) Once a Week, Documenting the Safety and Efficacy of Both Compounds During a 6-month Treatment, and Demonstrating the Neutralizing Effect of SSR29261 on the SSR126517E-induced Anti-Xa Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Venous Thrombosis
Keywords: Deep Venous Thrombosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-04-05
Enrollment: 757
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The three purposes of this study are the following:

* To compare during a 6-month treatment the safety and effectiveness of idrabiotaparinux (SSR126517) with that of idraparinux (SR34006), taking into account new events of deep venous thrombosis (DVT) and pulmonary embolism (PE), and bleeding risk;
* To compare the activities of idrabiotaparinux and idraparinux directly in blood during and after a 6-month treatment;
* To check the ability of avidin (SSR29261) to reverse the blood thinning activity of idrabiotaparinux at the end of a 6-month treatment period.

Detailed description: The study consists in a 6-month treatment period followed by an observational period of 3 to 6 months with a month 9 visit and a phone/contact visit at month 12.

All participants who complete the 6-month treatment period are re-randomized to either the idrabiotaparinux/idraparinux bioequipotency sub-study or the avidin neutralizing effect sub-study.

Eligibility criteria: Inclusion Criteria:

* Confirmed acute symptomatic DVT of the lower limbs

Exclusion Criteria:

* Severe concomitant diseases (e.g. renal failure, hepatic failure, uncontrolled hypertension)
* Active bleeding or high risk for bleeding.
* Pregnancy or childbearing potential without proper contraceptive measures.
* Breastfeeding
* Known allergy to idraparinux, SSR126517E, or egg proteins
* Indication of prolonged anticoagulation for other reason than DVT of the lower limbs
* Symptomatic pulmonary embolism (PE)
* Life expectancy \< 6 months.

Primary outcomes:
measure: Bioequipotency sub-study: idrabiotaparinux/idraparinux ratio for pharmacodynamic exposure parameters
timeFrame: Day 183
measure: Avidin neutralizing effect substudy: decrease in anti-Xa activity between the start and end of the avidin infusion
timeFrame: Day 183 to Day 188
Secondary outcomes:
measure: Pharmacokinetic profile: idrabiotaparinux and idraparinux plasma concentrations
timeFrame: Days 15, 36, 57, 92 and 183
measure: Safety: number of participants with clinically relevant bleedings and number of deaths as confirmed by a Central Independent Adjudication Committee (CIAC)
timeFrame: First 6 months
measure: Efficacy: number of participants with symptomatic recurrent venous thromboembolism as confirmed by the CIAC
timeFrame: First 6 months
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis
city: Vienna
country: Austria
facility: Sanofi-Aventis
city: Diegem
country: Belgium
facility: Sanofi-Aventis
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis
city: Laval
country: Canada
facility: Sanofi-Aventis
city: Praha
country: Czech Republic
facility: Sanofi-Aventis
city: Copenhagen
country: Denmark
facility: Sanofi-Aventis
city: Paris
country: France
facility: sanofi-aventis France
city: Natanya
country: Israel
facility: sanofi-aventis Israel
city: Milan
country: Italy
facility: Sanofi-aventis
city: Mexico
country: Mexico
facility: sanofi-aventis Mexico
city: Gouda
country: Netherlands
facility: sanofi-aventis, Netherlands
city: New Zealand
country: New Zealand
facility: Sanofi-Aventis
city: Warsawa
country: Poland
facility: Sanofi-Aventis
city: Moscow
country: Russian Federation
facility: Sanofi-aventis
city: Midrand
country: South Africa
facility: Sanofi-Aventis
city: Barcelona
country: Spain
facility: Sanofi-Aventis
city: Istanbul
country: Turkey
facility: sanofi-aventis Turkey
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References:
citation: Equinox Investigators. Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic deep venous thrombosis. J Thromb Haemost. 2011 Jan;9(1):92-9. doi: 10.1111/j.1538-7836.2010.04100.x.
citation: Trellu M, Fau JB, Cortez P, Cheng S, Paty I, Boelle E, Donat F, Sanderink GJ. Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis. Br J Clin Pharmacol. 2013 May;75(5):1255-64. doi: 10.1111/bcp.12009.
citation: Paty I, Trellu M, Destors JM, Cortez P, Boelle E, Sanderink G. Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Thromb Haemost. 2010 Apr;8(4):722-9. doi: 10.1111/j.1538-7836.2010.03746.x. Epub 2010 Jan 17.