A Study to Evaluate the Efficacy and Safety of Fondaparinux for the Prevention of Venous Blood Clots in Patients With a Plaster Cast or Other Type of Immobilization for a Below-knee Injury Not Needing Surgery

NCT00843492 | Completed Phase 3 Results

• 1 other identifier: 109350
• Study Type: interventional
• Target: 1,351
• Locations: 6 countries
• Sites: 122

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of fondaparinux in comparison with a heparin (nadroparin) in preventing deep vein thrombosis (blood clots in the leg veins), whether symptomatic or detected by ultrasound, and pulmonary embolism (blood clots that migrate to the lungs) in patients with leg injuries below the knee that require a cast or other type of immobilization but not surgery.

Conditions

Thrombosis, Venous

Keywords

deep vein thrombosis; immobilization; nadroparin; isolated lower-extremity injuries distal to the knee; plaster cast; non-surgical leg injury; venous thromboembolism; bleeding events; fondaparinux

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Venous Thromboembolism (VTE) or Death up to the Time of Complete Mobilization

  VTE is defined as asymptomatic deep vein thrombosis (DVT: the formation of a blood clot in a deep vein) detected by systematic compression ultrasonography, symptomatic DVT, or symptomatic fatal or non-fatal pulmonary embolism (PE). An embolism is a clot in the blood that forms and blocks a blood vessel. A pulmonary embolism is a blood clot that has travelled from elsewhere in the body through the blood stream to block the main artery of the lung or one of its branches. All venous thromboembolic events and deaths were adjudicated by the independent Central Adjudication Committee (CAC).

  Day 1 to complete mobilization plus 2 days (average of 35.9 study days)

Secondary Outcomes (6)

• Number of Participants With Any Adjudicated Components of VTE, Asymptomatic DVT, Symptomatic DVT, Symptomatic PE, and Death

  Day 1 to complete mobilization plus 2 days (average of 35.7 study days)

• Number of Participants With Confirmed VTE and Death up to the Final Visit or Contact

  Day 1 to 5 weeks (plus or minus 1 week) after complete mobilization (average of 67.8 study days)

• Number of Participants With Major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact

  Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

• Number of Participants With Clinically Relevant Non-major Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact

  Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

• Number of Participants With Minor Bleeding From Day 1 to Complete Mobilization and From Day 1 up to the Final Visit or Contact

  Day 1 to complete mobilization plus 4 days (average of 37.7 study days); Day 1 up to final visit or contact (average of 66.3 study days)

Study Arms (2)

Nadroparin

ACTIVE COMPARATOR

After randomization (Day 1), subjects will receive subcutaneously once daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days. Patients will then be followed up to five weeks (± one week) after the cast or brace removal.

Drug: Nadroparin

Fondaparinux

EXPERIMENTAL

After randomization (Day 1), subjects will receive subcutaneously, once daily, fondaparinux 2.5 mg (1.5 mg in patients with creatinine clearance between 30 and 50 mL/min) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days. Patients will then be followed up to five weeks (± one week) after the cast or brace removal.

Drug: Fondaparinux sodium

Interventions

Fondaparinux sodium DRUG

After randomization (Day 1), subjects will receive subcutaneously once daily fondaparinux 2.5 mg \[0.5mL\] (1.5 mg \[0.3mL\] in patients with creatinine clearance between 30 and 50 mL/min) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days.

Fondaparinux

Nadroparin DRUG

After randomization (Day 1), subjects will receive subcutaneously once daily nadroparin 2850 anti-Xa IU (0.3 mL) for at least 21 Days, up to complete mobilization, corresponding to cast or brace removal. The maximal duration of treatment is 45 days.

Nadroparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Requiring rigid or semi-rigid immobilization (e.g. with a plaster cast or brace) for at least 21 days and up to 45 days because of isolated non-surgical below-knee injury
• Presenting at least one of the following risk factors for venous thromboembolism: below-knee fracture or Achilles tendon rupture, age ≥40 years, body mass index \> 30 kg/m2, oestrogen-containing hormonal replacement therapy or oral contraception, active cancer (treatment ongoing or stopped for less than one year), history of VTE, congenital or acquired hypercoagulable state,
• Requiring thromboprophylaxis according to the Investigator's judgement up to complete mobilization (corresponding to cast or brace removal)
• Able and willing to provide written informed consent

You may not qualify if:

• Delay between injury and randomization greater than two days,
• Treatment with antithrombotic or anticoagulant therapy, including low-dose anticoagulation, for more than 2 days prior to randomization,
• Anticoagulant therapy required or likely to be required during the study period for another reason (e.g. planned surgery justifying pharmacological thromboprophylaxis, curative dose for treatment of VTE, etc.)
• Known hypersensitivity to fondaparinux or nadroparin or their excipient,
• Known history of heparin-induced thrombocytopenia,
• Women of childbearing potential not using a reliable contraceptive method throughout the study period,
• Women pregnant or breast-feeding during the study period.
• Active, clinically significant bleeding,
• Clinically significant bleeding within the past six months,
• Major surgery within the previous three months,
• Intraocular (other than cataract), spinal, and/or brain surgery within the previous twelve months,
• Haemorrhagic stroke within the previous twelve months,
• Severe head injury within the previous three months,
• Documented congenital or acquired bleeding tendency/disorder(s),
• Previous (within 12 months) or active or currently treated peptic ulcer disease,

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (122)

GSK Investigational Site

Agen, 47923, France

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GSK Investigational Site

Angers, 49100, France

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GSK Investigational Site

Antony, 92166, France

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GSK Investigational Site

Argenteuil, 95107, France

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GSK Investigational Site

Beauvais, 60021, France

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Bobigny, 93009, France

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GSK Investigational Site

Brest, 29609, France

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GSK Investigational Site

Cergy-Pontoise, 95303, France

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GSK Investigational Site

Clermont-Ferrand, 63000, France

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GSK Investigational Site

Colmar, 68024, France

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GSK Investigational Site

Créteil, 94010, France

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GSK Investigational Site

Grenoble, 38043, France

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GSK Investigational Site

Lille, 59037, France

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GSK Investigational Site

Lyon, 69275, France

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GSK Investigational Site

Lyon, 69365, France

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GSK Investigational Site

Lyon, 69437, France

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GSK Investigational Site

Mougins, 06250, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Orthez, 64301, France

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GSK Investigational Site

Paris, 75015, France

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GSK Investigational Site

Paris, 75181, France

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GSK Investigational Site

Paris, 75571, France

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GSK Investigational Site

Paris, 75651, France

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GSK Investigational Site

Paris, 75679, France

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GSK Investigational Site

Pringy, 74374, France

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GSK Investigational Site

Rennes, 35033, France

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GSK Investigational Site

Roanne, 42300, France

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GSK Investigational Site

Rouen, 76031, France

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GSK Investigational Site

Saint-Pierre, 97448, France

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GSK Investigational Site

Sainte Colombe Les Vienne, 69560, France

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GSK Investigational Site

Saintes, 17108, France

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Toulouse, 31059, France

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GSK Investigational Site

Valenciennes, 59300, France

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Erlangen, Bavaria, 91054, Germany

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Munich, Bavaria, 80335, Germany

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Munich, Bavaria, 80339, Germany

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Hamburg, Hamburg, 20246, Germany

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Hamburg, Hamburg, 22415, Germany

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Wiesbaden, Hesse, 65191, Germany

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Hanover, Lower Saxony, 30625, Germany

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Gevelsberg, North Rhine-Westphalia, 58285, Germany

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Moers, North Rhine-Westphalia, 47441, Germany

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Dresden, Saxony, 01187, Germany

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Dresden, Saxony, 01307, Germany

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Schmiedeberg, Saxony, 01762, Germany

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Zwickau, Saxony, 08060, Germany

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Zerbst, Saxony-Anhalt, 39261, Germany

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Lübeck, Schleswig-Holstein, 23538, Germany

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Berlin, State of Berlin, 10559, Germany

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Berlin, State of Berlin, 12627, Germany

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Berlin, State of Berlin, 13353, Germany

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Altenburg, Thuringia, 04600, Germany

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Bologna, Emilia-Romagna, 40136, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Latina, Lazio, 04100, Italy

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Rome, Lazio, 00141, Italy

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Genoa, Liguria, 16132, Italy

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Bergamo, Lombardy, 24128, Italy

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Milan, Lombardy, 20161, Italy

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Orbassano (TO), Piedmont, 10043, Italy

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Catania, Sicily, 95126, Italy

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Siena, Tuscany, 53100, Italy

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Conegliano (TV), Veneto, 31015, Italy

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Padua, Veneto, 35128, Italy

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Amersfoort, 3818 ES, Netherlands

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Eindhoven, 5623 EJ, Netherlands

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Maastricht, 6229 HX, Netherlands

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GSK Investigational Site

Sittard-geleen, 6162 BG, Netherlands

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Utrecht, 3582 KE, Netherlands

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Venlo, 5912 BL, Netherlands

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Barnaul, 656024, Russia

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GSK Investigational Site

Irkutsk, 664003, Russia

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GSK Investigational Site

Kemerovo, 650002, Russia

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GSK Investigational Site

Kursk, 305035, Russia

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GSK Investigational Site

Moscow, 125299, Russia

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GSK Investigational Site

Novosibirsk, 630117, Russia

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GSK Investigational Site

Perm, 614036, Russia

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GSK Investigational Site

Ryazan, 390026, Russia

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GSK Investigational Site

Saint Petersburg, 198260, Russia

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GSK Investigational Site

Saint Petersburgh, 192242, Russia

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GSK Investigational Site

Samara, 443010, Russia

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GSK Investigational Site

Samara, 443095, Russia

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GSK Investigational Site

Stavropol, 355030, Russia

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GSK Investigational Site

Tomsk, 634063, Russia

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GSK Investigational Site

Tver', 170036, Russia

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GSK Investigational Site

Tyumen, 625023, Russia

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GSK Investigational Site

Ufa, 450000, Russia

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GSK Investigational Site

Yaroslavl, 150003, Russia

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GSK Investigational Site

Yaroslavl, 150023, Russia

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GSK Investigational Site

Yekaterinburg, 620039, Russia

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GSK Investigational Site

Yekaterinburg, 620102, Russia

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GSK Investigational Site

A Coruña, 15006, Spain

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GSK Investigational Site

Aravaca, 28023, Spain

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GSK Investigational Site

Avilés/Asturias, 33400, Spain

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GSK Investigational Site

Barcelona, 08006, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Castellon, 12004, Spain

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GSK Investigational Site

Córdoba, 14004, Spain

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GSK Investigational Site

Don Benito/Badajoz, 06400, Spain

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GSK Investigational Site

Ferrol. La Coruña, 15405, Spain

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GSK Investigational Site

Getafe/Madrid, 28905, Spain

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GSK Investigational Site

Jaén, 23007, Spain

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GSK Investigational Site

Linares, 23700, Spain

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GSK Investigational Site

Lugo, 27004, Spain

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GSK Investigational Site

Madrid, 28006, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28040, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Majadahonda/Madrid, 28220, Spain

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GSK Investigational Site

Mondragón - Guipúzcoa, 20500, Spain

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GSK Investigational Site

Ourense, 32005, Spain

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GSK Investigational Site

Palencia, 340014, Spain

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GSK Investigational Site

Palma de Mallorca, 07010, Spain

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GSK Investigational Site

Pozoblanco/Córdoba, 14400, Spain

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GSK Investigational Site

San Sebastián de Los Reyes/Madrid, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Seville, 41071, Spain

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GSK Investigational Site

Torrelodones/Madrid, 28250, Spain

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GSK Investigational Site

Torrevieja, 03184, Spain

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GSK Investigational Site

Valdemoro/Madrid, 28340, Spain

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GSK Investigational Site

Vigo/Pontevedra, 36200, Spain

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MeSH Terms

Conditions

Venous Thrombosis; Venous Thromboembolism

Interventions

Fondaparinux; Nadroparin

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism

Intervention Hierarchy (Ancestors)

Oligosaccharides; Polysaccharides; Carbohydrates; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: February 13, 2009
• Study Start: December 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 16, 2016
• Results First Posted: July 18, 2012

Record last verified: 2014-02

Locations

ES (30); DE (20); IT (12); RU (21); FR (33); NL (6)