Evaluation of AVE5026 in the Prevention of Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy (SAVE-ONCO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00694382
First received: May 7, 2008
Last updated: January 14, 2013
Last verified: January 2013

May 7, 2008
January 14, 2013
June 2008
November 2010   (final data collection date for primary outcome measure)
  • Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or VTE-related Death [ Time Frame: From randomization up to 3 days after last study drug injection ] [ Designated as safety issue: No ]

    VTE included any symptomatic Deep Vein Thrombosis [DVT] of lower or upper limbs and any non-fatal Pulmonary Embolism [PE] as confirmed by a Central Independent Adjudication Committee [CIAC] after review of compression ultrasound or venography for DVT, ventilation/perfusion lung scan, pulmonary angiogram or spiral computer tomography lung scan for PE.

    VTE-related death included fatal PE and unexplained deaths without confirmatory autopsy. Any sudden death could be classified as fatal PE by the CIAC unless diagnostic test results strongly indicated an alternative diagnosis".

  • Time-to-first Occurrence of VTE or VTE-related Death (Cumulative Incidence Function) [ Time Frame: From randomization up to 3 days after last study drug injection ] [ Designated as safety issue: No ]
    Participants alive and not having experienced VTE were right censored at last study drug injection plus 3 days. In order to correct for competing risks (Deaths other than VTE-related death), a model of cause-specific hazards was used to estimate the Cumulative incidence Function with Prentice non-parametric estimator.
Time-to-first occurrence of symptomatic Deep Venous Thrombosis of lower or upper limbs, non fatal Pulmonary embolism, and VTE-related deaths [ Time Frame: From randomization up to 3 calendar days after last study drug injection ]
Complete list of historical versions of study NCT00694382 on ClinicalTrials.gov Archive Site
  • Percentage of Participants who required the initiation of curative anticoagulant or thrombolytic treatment after VTE assessment [ Time Frame: From randomization up to 3 days after last study drug injection ] [ Designated as safety issue: No ]
    Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answer to the question "was the subject treated for VTE?" asked after diagnostic tests for suspected VTE and after lung imaging test for tumor evaluation.
  • Percentage of Participants Who Experienced Clinically Relevant Bleedings [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    Clinically Relevant Bleedings included overt bleedings classified by the CIAC as:

    • "major" (fatal, in a critical area/organ, causing a drop in hemoglobin ≥2 g/dL or requiring transfusion ≥2 units of blood)
    • "clinically relevant non-major" (requiring medical intervention and not meeting criteria for major bleeding).
  • Overall survival [OS] [ Time Frame: From randomization up to 1 year after randomization or 7 months following randomization of the last participant, whichever came first ] [ Designated as safety issue: No ]

    Survival status was collected for all participants either one year after randomization, or at the study end date, (ie, 7 months following randomization of the last patient), whichever came first.

    OS was defined as the time from date of randomization to date of death due to any cause. Participants alive were censored at last date of contact that they were known to be alive.

  • Efficacy: individual components of the primary outcome measure [ Time Frame: From randomization up to 3 calendar days after last study drug injection ]
  • Safety: bleedings, transfusions, laboratory data, adverse events, deaths [ Time Frame: Study period ]
  • Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA] [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    PCSA are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

    Thresholds for platelet counts were defined as follows:

    • Platelets count <50 Giga/L;
    • Platelets count ≥50 and <100 Giga/L;
  • Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA] [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    Thresholds were defined as follows:

    • Alanine Aminotransferase [ALAT] >3 Upper Normal Limit [ULN];
    • Total Bilirubin [TB] >2 ULN;
    • ALAT >3 ULN and TB >2 ULN;

    Cases with ALAT >3 ULN and TB >2 ULN (not necessarily concomitant) were evaluated by blinded independent adjudicator to determine if they met Hy's law criteria.

Not Provided
 
Evaluation of AVE5026 in the Prevention of Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy
A Multinational, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AVE5026 in the Prevention of Venous Thromboembolism (VTE) in Cancer Patients at High Risk for VTE and Who Are Undergoing Chemotherapy

The primary objective was to compare the efficacy of once daily subcutaneous injections of Semuloparin sodium (AVE5026) with placebo in the prevention of venous thromboembolism [VTE] in cancer patients at high risk for VTE and who were undergoing chemotherapy.

The secondary objectives were to evaluate the safety of Semuloparin sodium (AVE5026), to document Semuloparin sodium (AVE5026) exposures, to try identifying a metagene predictor of VTE and to assess the survival status at one year in this population.

Randomization had to take place just prior to the first study drug injection (randomization ratio 1:1).

The study period per participant was variable depending on the duration of chemotherapy. It included:

  • a screening period up to 3 weeks,
  • a double-blind treatment period,
  • a follow-up period of 1 month.

Study end date was at the latest 7 months following the randomization of the last participant (6 months treatment and 1 month follow-up).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Venous Thromboembolism
  • Cancer
  • Drug: Semuloparin sodium

    0.4 mL solution in ready-to-use 0.5 ml pre-filled syringe

    Subcutaneous injection

    Other Name: AVE5026
  • Drug: Placebo (for semuloparin)

    0.4 mL solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component

    Subcutaneous injection

  • Experimental: Semuloparin
    Semuloparin sodium 20 mg once daily until change in chemotherapy regimen
    Intervention: Drug: Semuloparin sodium
  • Placebo Comparator: Placebo
    Placebo (for semuloparin) once daily until change in chemotherapy regimen
    Intervention: Drug: Placebo (for semuloparin)
Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, Mouret P, Chaudhari U, Lawson F, Turpie AG; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012 Feb 16;366(7):601-9. doi: 10.1056/NEJMoa1108898.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3212
November 2010
November 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

Cancer patient with metastatic or locally advanced solid tumor of lung, pancreas, stomach, colon/rectum, bladder or ovary initiating a (new) course of chemotherapy with a minimum intent of 3 months therapy

Exclusion Criteria:

  • Required systematic venous thromboprophylaxis or curative treatment with anti-coagulant or thrombolytic;
  • High risk of bleeding;
  • Severe renal impairment (estimated creatinine clearance <30 mL/min);
  • ECOG (Eastern Cooperative Oncology Group) performance status 3 & 4;
  • Major surgery within 4 weeks before randomization;
  • Known hypersensitivity to unfractionated heparin [UFH] or low molecular weight heparin [LMWH].

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belarus,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Croatia,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Indonesia,   Ireland,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Norway,   Peru,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Slovakia,   Slovenia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Ukraine,   United Kingdom
 
NCT00694382
EFC6521, 2007-007943-29
Yes
Sanofi
Sanofi
Not Provided
Study Chair: Alexander Turpie, MD HHS-General Hospital, Hamilton, Canada
Principal Investigator: Giancarlo Agnelli, MD University of Perugia, Italy
Sanofi
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP