Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement.
Circulation
; 104(1): 74-8, 2001 Jul 03.
Article
de En
| MEDLINE
| ID: mdl-11435341
ABSTRACT
BACKGROUND:
With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS ANDRESULTS:
This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded =48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding =72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%.CONCLUSIONS:
A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Complications postopératoires
/
Facteur VIIa
/
Protéines d'helminthes
/
Arthroplastie prothétique de genou
/
Thrombose veineuse
/
Anticoagulants
Type d'étude:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Aged
/
Female
/
Humans
/
Male
Pays/Région comme sujet:
America do norte
/
Europa
Langue:
En
Journal:
Circulation
Année:
2001
Type de document:
Article
Pays d'affiliation:
Canada