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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).

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00038961
First received: June 5, 2002
Last updated: August 31, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
Thromboembolism
Drug: fondaparinux sodium
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • venous thromboembolism (VTE) [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: first study drug injection to 2 days after last study drug injection and first study drug injection up to Day 32 ] [ Designated as safety issue: Yes ]
    adjudicated major bleeding


Secondary Outcome Measures:
  • deep vein thrombosis (DVT) [ Time Frame: up to Day 10 ] [ Designated as safety issue: No ]
    Incidence of any DVT, any proximal DVT, and distal only DVT

  • symptomatic VTE (venous thromboembolism) [ Time Frame: up to Day 10 and up to Day 32 ] [ Designated as safety issue: No ]
    Incidence of adjudicated symptomatic VTE (DVT, non fatal pulmonary embolism (PE), and fatal PE)

  • initiation of curative treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Initiation of curative treatment after VTE assessment used for the primary endpoint evaluation

  • any VTE and all deaths [ Time Frame: up to Day 10 ] [ Designated as safety issue: No ]
    incidence of any VTE and all deaths

  • symptomatic VTE and all deaths [ Time Frame: up to Day 32 ] [ Designated as safety issue: No ]
    incidence of adjudicated symptomatic VTE and all deaths

  • minor bleeding [ Time Frame: treatment period and up to day 32 ] [ Designated as safety issue: Yes ]
    adjudicated minor bleeding

  • All major or minor bleeding [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    All adjudicated (major or minor) bleeding

  • Adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs/serious adverse events (SAEs))

  • Transfusion [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    the need for transfusion and total blood units transfused

  • Lab parameters [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    changes from baseline in laboratory parameters

  • Death [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Death


Enrollment: 1309
Study Start Date: November 2001
Study Completion Date: October 2004
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + intermittent pneumatic compression (IPC) Other: placebo
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)
Experimental: fondaparinux + intermittent pneumatic compression (IPC) Drug: fondaparinux sodium
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)

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.

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038961

Sponsors and Collaborators
GlaxoSmithKline
Sanofi
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 103414
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00038961     History of Changes
Other Study ID Numbers: 103414 
Study First Received: June 5, 2002
Last Updated: August 31, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
fondaparinux sodium
DVT Prevention
abdominal surgery
VTE prevention
venous thromboembolism
pulmonary embolism

Additional relevant MeSH terms:
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Fondaparinux
PENTA
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 07, 2016