Thromboembolism
Conditions
Keywords
fondaparinux sodium, DVT Prevention, abdominal surgery, VTE prevention, venous thromboembolism, pulmonary embolism
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.
Interventions
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)
OTHERplacebo
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)
Sponsors
Sanofi
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| venous thromboembolism (VTE) | 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 | 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 | first study drug injection to 2 days after last study drug injection and first study drug injection up to Day 32 | adjudicated major bleeding |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| initiation of curative treatment | 3 years | Initiation of curative treatment after VTE assessment used for the primary endpoint evaluation |
| any VTE and all deaths | up to Day 10 | incidence of any VTE and all deaths |
| symptomatic VTE and all deaths | up to Day 32 | incidence of adjudicated symptomatic VTE and all deaths |
| minor bleeding | treatment period and up to day 32 | adjudicated minor bleeding |
| deep vein thrombosis (DVT) | up to Day 10 | Incidence of any DVT, any proximal DVT, and distal only DVT |
| Adverse events | 3 years | Adverse Events (AEs/serious adverse events (SAEs)) |
| Transfusion | 3 years | the need for transfusion and total blood units transfused |
| Lab parameters | 3 years | changes from baseline in laboratory parameters |
| Death | 3 years | Death |
| All major or minor bleeding | 3 years | All adjudicated (major or minor) bleeding |
| symptomatic VTE (venous thromboembolism) | up to Day 10 and up to Day 32 | Incidence of adjudicated symptomatic VTE (DVT, non fatal pulmonary embolism (PE), and fatal PE) |
Outcome results
None listed