Document Detail


Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.
MedLine Citation:
PMID:  22047559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established.
METHODS: We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (±15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [±15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period.
RESULTS: Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P<0.001), a 61% reduction in hemarthroses (P<0.001), and a 72% reduction in target-joint bleeding (≥3 hemarthroses in a single joint during a 6-month treatment period) (P<0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug.
CONCLUSIONS: AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.).
Authors:
Cindy Leissinger; Alessandro Gringeri; Bülent Antmen; Erik Berntorp; Chiara Biasoli; Shannon Carpenter; Paolo Cortesi; Hyejin Jo; Kaan Kavakli; Riitta Lassila; Massimo Morfini; Claude Négrier; Angiola Rocino; Wolfgang Schramm; Margit Serban; Marusia Valentina Uscatescu; Jerzy Windyga; Bülent Zülfikar; Lorenzo Mantovani
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  365     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-03     Completed Date:  2011-11-23     Revised Date:  2011-12-22    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1684-92     Citation Subset:  AIM; IM    
Affiliation:
Louisiana Center for Bleeding and Clotting Disorders, Tulane University, New Orleans, LA, USA. cleissi@tulane.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00221195
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Blood Coagulation Factors / administration & dosage*,  adverse effects
Child
Child, Preschool
Cross-Over Studies
Drug Administration Schedule
Factor VIII / administration & dosage,  antagonists & inhibitors
Female
Hemophilia A / complications,  drug therapy*
Hemorrhage / prevention & control*
Humans
Male
Middle Aged
Prospective Studies
Statistics, Nonparametric
Young Adult
Chemical
Reg. No./Substance:
0/Blood Coagulation Factors; 78690-39-8/Feiba; 9001-27-8/Factor VIII
Comments/Corrections
Erratum In:
N Engl J Med. 2011 Dec 22;365(25):2441

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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