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).

Thromboembolism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00038961
• Other study ID #: 103414
• Status: Completed
• Phase: Phase 3
• First received: June 5, 2002
• Last updated: August 31, 2016
• Start date: November 2001
• Est. completion date: October 2004

Study information

• Verified date: August 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1309
• Est. completion date: October 2004
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Thromboembolism

Intervention

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)

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)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Sanofi

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	No
Primary	major bleeding	adjudicated major bleeding	first study drug injection to 2 days after last study drug injection and first study drug injection up to Day 32	Yes
Secondary	deep vein thrombosis (DVT)	Incidence of any DVT, any proximal DVT, and distal only DVT	up to Day 10	No
Secondary	symptomatic VTE (venous thromboembolism)	Incidence of adjudicated symptomatic VTE (DVT, non fatal pulmonary embolism (PE), and fatal PE)	up to Day 10 and up to Day 32	No
Secondary	initiation of curative treatment	Initiation of curative treatment after VTE assessment used for the primary endpoint evaluation	3 years	No
Secondary	any VTE and all deaths	incidence of any VTE and all deaths	up to Day 10	No
Secondary	symptomatic VTE and all deaths	incidence of adjudicated symptomatic VTE and all deaths	up to Day 32	No
Secondary	minor bleeding	adjudicated minor bleeding	treatment period and up to day 32	Yes
Secondary	All major or minor bleeding	All adjudicated (major or minor) bleeding	3 years	Yes
Secondary	Adverse events	Adverse Events (AEs/serious adverse events (SAEs))	3 years	Yes
Secondary	Transfusion	the need for transfusion and total blood units transfused	3 years	Yes
Secondary	Lab parameters	changes from baseline in laboratory parameters	3 years	Yes
Secondary	Death	Death	3 years	Yes

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