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A Study to Evaluate the Efficacy and Safety of Fondaparinux Sodium When Used With Intermittent Pneumatic Compression to Prevent Venous Thromboembolic (IPC) Versus IPC Alone for the Prevention of Venous Thromboembolic Events in Subjects at Increased Risk Undergoing Major Abdominal Surgery (APOLLO).

Primary Purpose

Thromboembolism

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
fondaparinux sodium
placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Thromboembolism focused on measuring fondaparinux sodium, DVT Prevention, abdominal surgery, VTE prevention, venous thromboembolism, pulmonary embolism

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Undergoing abdominal surgery (any surgery between the diaphragm and pelvic floor) lasting longer than 45 minutes (duration from anesthesia induction to surgical closure) Over 40 years of age Subject who had signed the informed consent. Exclusion Criteria: Active, clinically significant bleeding Documented congenital or acquired bleeding tendency/disorders Active ulcerative gastrointestinal disease unless the reason for the present surgery. Recent intracranial hemorrhage or recent (less than 3 months prior to randomisation) brain, spinal, or ophthalmologic surgery. Indwelling intrathecal or epidural catheters for more than 6 hours after surgical closure. Subjects who had a traumatic puncture or unusual difficulty in applying the catheter Known cerebral metastasis, Subjects in whom hemostasis had not been established 6 hours after surgical closure, Current thrombocytopenia, Bacterial endocarditis Creatinine level above 2.0 mg/dL (180 μmol/L) in a well-hydrated subject, Documented hypersensitivity to contrast media, Use of any contraindicated drug that could not be combined with the injection of contrast medium, Patent with evidence of leg ischemia caused by peripheral vascular disease, unable to undergo IPC and unable to wear Elastic Stockings. Exclusion criteria related to trial methodology: Mental disorders that could interfere with study participation and/or failure to give written informed consent to take part in the study, Subject's life expectancy < 6 months, Clinical sign of DVT and/or history of recent DVT, Participation in any other therapeutic drug study or a device study evaluating DVT prophylaxis within 90 days preceding inclusion, Previous participation in a study of fondaparinux sodium, Known hypersensitivity to fondaparinux and its excipients, Current addictive disorders that could interfere with study participation, Administration of heparin, heparinoids, LMWH, oral anticoagulants, dextrans, hirudin, fibrinolytic agents or drugs blocking glycoprotein platelet receptors (GPIIb-IIIa) during the screening period, i.e., from admission to surgery, Subjects for whom anticoagulant therapy was contraindicated or who had, due to concomitant disease, an indication for oral anticoagulant or heparins (including LMWH) and who could not discontinue those treatments, Women of child-bearing potential: women not using an appropriate contraceptive method during the whole duration of study participation , Subject with body weight <50 kg, Subjects, who in the opinion of the investigator, required a pharmacological prophylaxis in addition to intermittent pneumatic compression, Known pregnancy and / or women who intended to breastfeed, Subjects undergoing vascular surgery such as aorto-femoral bypass graft

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Placebo + intermittent pneumatic compression (IPC)

    fondaparinux + intermittent pneumatic compression (IPC)

    Arm Description

    Outcomes

    Primary Outcome Measures

    venous thromboembolism (VTE)
    the incidence of VTE determined as any of the following VTE outcomes recorded up to the first venogram performed or up to Day 10, whichever occurred first: adjudicated manadatory veongram positive for DVT between Day 5 and Day 10; adjudicated symptomatic DVT and/or adjudicated non-fatal PE; adjudicated fatal PE
    major bleeding
    adjudicated major bleeding

    Secondary Outcome Measures

    deep vein thrombosis (DVT)
    Incidence of any DVT, any proximal DVT, and distal only DVT
    symptomatic VTE (venous thromboembolism)
    Incidence of adjudicated symptomatic VTE (DVT, non fatal pulmonary embolism (PE), and fatal PE)
    initiation of curative treatment
    Initiation of curative treatment after VTE assessment used for the primary endpoint evaluation
    any VTE and all deaths
    incidence of any VTE and all deaths
    symptomatic VTE and all deaths
    incidence of adjudicated symptomatic VTE and all deaths
    minor bleeding
    adjudicated minor bleeding
    All major or minor bleeding
    All adjudicated (major or minor) bleeding
    Adverse events
    Adverse Events (AEs/serious adverse events (SAEs))
    Transfusion
    the need for transfusion and total blood units transfused
    Lab parameters
    changes from baseline in laboratory parameters
    Death
    Death

    Full Information

    First Posted
    June 5, 2002
    Last Updated
    August 31, 2016
    Sponsor
    GlaxoSmithKline
    Collaborators
    Sanofi
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00038961
    Brief Title
    A Study to Evaluate the Efficacy and Safety of Fondaparinux Sodium When Used With Intermittent Pneumatic Compression to Prevent Venous Thromboembolic (IPC) Versus IPC Alone for the Prevention of Venous Thromboembolic Events in Subjects at Increased Risk Undergoing Major Abdominal Surgery (APOLLO).
    Official Title
    A Multicenter, Randomized, Double-blind, Parallel Group Trial to Demonstrate the Efficacy of Fondaparinux Sodium in Association With Intermittent Pneumatic Compression (IPC) Versus IPC Used Alone for the Prevention of Venous Thromboembolic Events in Subjects at Increased Risk Undergoing Major Abdomi
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2016
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2001 (undefined)
    Primary Completion Date
    October 2004 (Actual)
    Study Completion Date
    October 2004 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    GlaxoSmithKline
    Collaborators
    Sanofi

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a multicentre, randomized, double-blind, placebo controlled study. During this study all the patients will receive background venous thromboembolism (VTE) mechanical prophylaxis with intermittent pneumatic compression (IPC).
    Detailed Description
    This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of fondaparinux in the prevention of venous thromboembolism (VTE) in subjects undergoing abdominal surgery at increased risk for VTE. During this study all subjects were to receive background VTE prophylaxis with intermittent pnuematic compression (IPC) ± elastic stockings (ES). Screening Period ( Day -30-Day 0) all subjects at increased risk of VTE undergoing abdominal surgery and fulfilled the study entry criteria were eligible for the study. Treatment Period (Day 7 ±2): At the baseline assessment on the day of surgery (Day 1) subjects who satisfied all inclusion/exclusion criteria were randomized (1:1) to receive either fondaparinux or placebo. All the subjects were to receive background therapy with IPC ±ES. The first administration of either fondaparinux 2.5mg or placebo was to take place 6 to 8 hours after surgical closure provided hemostasis was achieved. Thereafter a once daily subcutaneous injection of either fondaparinux 2.5mg or placebo was to be administered up to Day 7 ±2. During the treatment phase, subjects were assessed daily. A mandatory venogram was performed between Day 5 and 10 or earlier in the case of symptomatic VTE, but not more than 1 calendar day after the last study treatment administration. Follow up Period (Day 30 ±2): A follow-up visit or contact was to take place at Day 30 ±2 days. Use of antithrombotic therapy for prevention of VTE after the mandatory venographyand during the entire Follow-up Period was left to the investigator's discretion.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Thromboembolism
    Keywords
    fondaparinux sodium, DVT Prevention, abdominal surgery, VTE prevention, venous thromboembolism, pulmonary embolism

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    1309 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo + intermittent pneumatic compression (IPC)
    Arm Type
    Placebo Comparator
    Arm Title
    fondaparinux + intermittent pneumatic compression (IPC)
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    fondaparinux sodium
    Intervention Description
    2.5 mg fondparinux sodium, daily, s.c. starting 6 to 8 hours after surgical closure for up to 7 +/- 2 days, administered on top of IPC +/- elastic stockings (ES)
    Intervention Type
    Other
    Intervention Name(s)
    placebo
    Intervention Description
    placebo, daily, s.c. starting 6 to 8 hours after surgical closure for up to 7 +/- 2 days, administered on top of IPC +/- elastic stockings (ES)
    Primary Outcome Measure Information:
    Title
    venous thromboembolism (VTE)
    Description
    the incidence of VTE determined as any of the following VTE outcomes recorded up to the first venogram performed or up to Day 10, whichever occurred first: adjudicated manadatory veongram positive for DVT between Day 5 and Day 10; adjudicated symptomatic DVT and/or adjudicated non-fatal PE; adjudicated fatal PE
    Time Frame
    adjudicated mandatory venogram positive for DVT between day 5 and day 10; up to day 10 for symptomatic DVT and/or adjudicated non fatal Pe , adjudicated fatal PE
    Title
    major bleeding
    Description
    adjudicated major bleeding
    Time Frame
    first study drug injection to 2 days after last study drug injection and first study drug injection up to Day 32
    Secondary Outcome Measure Information:
    Title
    deep vein thrombosis (DVT)
    Description
    Incidence of any DVT, any proximal DVT, and distal only DVT
    Time Frame
    up to Day 10
    Title
    symptomatic VTE (venous thromboembolism)
    Description
    Incidence of adjudicated symptomatic VTE (DVT, non fatal pulmonary embolism (PE), and fatal PE)
    Time Frame
    up to Day 10 and up to Day 32
    Title
    initiation of curative treatment
    Description
    Initiation of curative treatment after VTE assessment used for the primary endpoint evaluation
    Time Frame
    3 years
    Title
    any VTE and all deaths
    Description
    incidence of any VTE and all deaths
    Time Frame
    up to Day 10
    Title
    symptomatic VTE and all deaths
    Description
    incidence of adjudicated symptomatic VTE and all deaths
    Time Frame
    up to Day 32
    Title
    minor bleeding
    Description
    adjudicated minor bleeding
    Time Frame
    treatment period and up to day 32
    Title
    All major or minor bleeding
    Description
    All adjudicated (major or minor) bleeding
    Time Frame
    3 years
    Title
    Adverse events
    Description
    Adverse Events (AEs/serious adverse events (SAEs))
    Time Frame
    3 years
    Title
    Transfusion
    Description
    the need for transfusion and total blood units transfused
    Time Frame
    3 years
    Title
    Lab parameters
    Description
    changes from baseline in laboratory parameters
    Time Frame
    3 years
    Title
    Death
    Description
    Death
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Undergoing abdominal surgery (any surgery between the diaphragm and pelvic floor) lasting longer than 45 minutes (duration from anesthesia induction to surgical closure) Over 40 years of age Subject who had signed the informed consent. Exclusion Criteria: Active, clinically significant bleeding Documented congenital or acquired bleeding tendency/disorders Active ulcerative gastrointestinal disease unless the reason for the present surgery. Recent intracranial hemorrhage or recent (less than 3 months prior to randomisation) brain, spinal, or ophthalmologic surgery. Indwelling intrathecal or epidural catheters for more than 6 hours after surgical closure. Subjects who had a traumatic puncture or unusual difficulty in applying the catheter Known cerebral metastasis, Subjects in whom hemostasis had not been established 6 hours after surgical closure, Current thrombocytopenia, Bacterial endocarditis Creatinine level above 2.0 mg/dL (180 μmol/L) in a well-hydrated subject, Documented hypersensitivity to contrast media, Use of any contraindicated drug that could not be combined with the injection of contrast medium, Patent with evidence of leg ischemia caused by peripheral vascular disease, unable to undergo IPC and unable to wear Elastic Stockings. Exclusion criteria related to trial methodology: Mental disorders that could interfere with study participation and/or failure to give written informed consent to take part in the study, Subject's life expectancy < 6 months, Clinical sign of DVT and/or history of recent DVT, Participation in any other therapeutic drug study or a device study evaluating DVT prophylaxis within 90 days preceding inclusion, Previous participation in a study of fondaparinux sodium, Known hypersensitivity to fondaparinux and its excipients, Current addictive disorders that could interfere with study participation, Administration of heparin, heparinoids, LMWH, oral anticoagulants, dextrans, hirudin, fibrinolytic agents or drugs blocking glycoprotein platelet receptors (GPIIb-IIIa) during the screening period, i.e., from admission to surgery, Subjects for whom anticoagulant therapy was contraindicated or who had, due to concomitant disease, an indication for oral anticoagulant or heparins (including LMWH) and who could not discontinue those treatments, Women of child-bearing potential: women not using an appropriate contraceptive method during the whole duration of study participation , Subject with body weight <50 kg, Subjects, who in the opinion of the investigator, required a pharmacological prophylaxis in addition to intermittent pneumatic compression, Known pregnancy and / or women who intended to breastfeed, Subjects undergoing vascular surgery such as aorto-femoral bypass graft
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GSK Clinical Trials
    Organizational Affiliation
    GlaxoSmithKline
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
    Citations:
    PubMed Identifier
    17723125
    Citation
    Turpie AG, Bauer KA, Caprini JA, Comp PC, Gent M, Muntz JE; Apollo Investigators. Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. J Thromb Haemost. 2007 Sep;5(9):1854-61. doi: 10.1111/j.1538-7836.2007.02657.x.
    Results Reference
    result
    Links:
    URL
    https://www.clinicalstudydatarequest.com
    Description
    Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
    Available IPD and Supporting Information:
    Available IPD/Information Type
    Statistical Analysis Plan
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register
    Available IPD/Information Type
    Study Protocol
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register
    Available IPD/Information Type
    Individual Participant Data Set
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register
    Available IPD/Information Type
    Dataset Specification
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register
    Available IPD/Information Type
    Informed Consent Form
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register
    Available IPD/Information Type
    Clinical Study Report
    Available IPD/Information URL
    https://www.clinicalstudydatarequest.com
    Available IPD/Information Identifier
    103414
    Available IPD/Information Comments
    For additional information about this study please refer to the GSK Clinical Study Register

    Learn more about this trial

    A Study to Evaluate the Efficacy and Safety of Fondaparinux Sodium When Used With Intermittent Pneumatic Compression to Prevent Venous Thromboembolic (IPC) Versus IPC Alone for the Prevention of Venous Thromboembolic Events in Subjects at Increased Risk Undergoing Major Abdominal Surgery (APOLLO).

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