Idraparinux: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
m (Robot: Automated text replacement (-{{SIB}} + & -{{EH}} + & -{{EJ}} + & -{{Editor Help}} + & -{{Editor Join}} +))
 
(13 intermediate revisions by 2 users not shown)
Line 50: Line 50:
{{CMG}}
{{CMG}}


{{Editor Help}}




Idraparinux  sodium is a novel long-acting synthetic highly potent  synthetic and  specific indirect inhibitor of coagulation factor Xa,  injectable  subcutaneously. Its long-duration of action makes it  suitable for weekly administration. '''Idraparinux sodium''' is an [[anticoagulant]] medication in development by [[Sanofi-Aventis]].<ref name="pmid18294998">{{cite journal |author=Bousser MG, Bouthier J, Büller HR, ''et al.'' |title=Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial |journal=Lancet |volume=371 |issue=9609 |pages=315–21 |year=2008 |month=January |pmid=18294998 |doi=10.1016/S0140-6736(08)60168-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)60168-3}}</ref>
==Overview==
 
Idraparinux  sodium is a novel long-acting synthetic indirect inhibitor of coagulation [[factor Xa]]<ref name="pmid18294998">{{cite journal |author=Bousser MG, Bouthier J, Büller HR, ''et al.'' |title=Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial |journal=Lancet |volume=371 |issue=9609 |pages=315–21 |year=2008 |month=January |pmid=18294998 |doi=10.1016/S0140-6736(08)60168-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)60168-3}}</ref>. The agent is being developed by [[Sanofi-Aventis]].  It has a similar chemical structure and mechanism of action as [[fondaparinux]], but its elimination half-life of 80 hours is 5 to 6 times longer than that of fondaparix (17 hours). Given its long [[half life]], it can be injected [[subcutaneously]] once a week.
It has a similar chemical structure and the same method of action as [[fondaparinux]], but with an elimination half-life about five to six times longer (an increase from fondaparinux's 17 hours to approximately 80 hours), which means that the drug should only need to be injected once a week.
 


==Use in Atrial Fibrillation==
==Use in Atrial Fibrillation==


===The AMADEUS study===
===The AMADEUS study===
The  phase III AMADEUS study was a randomized, open label trial designed to  compare the efficacy and safety of once-a-week idraparinux versus oral VKA treatment for the long-term prevention of thromboembolic  events (stroke and non-central nervous system systemic embolism) in  patients with AF and at least one additional risk factor for stroke. The  predefined risk factors were previous ischemic stroke, transient ischemic attack or SE, hypertension  requiring drug treatment, left ventricular dysfunction, age >75  years, age between 65-75 years plus diabetes mellitus, or age between  65-75 years plus symptomatic coronary heart disease.
The  phase III AMADEUS study was a randomized, open label trial designed to  compare the efficacy and safety of once-a-week idraparinux versus oral VKA treatment for the long-term prevention of thromboembolic  events (stroke and non-central nervous system systemic embolism) in  patients with AF and at least one additional risk factor for stroke. The  predefined risk factors were previous ischemic stroke, transient ischemic attack or SE, hypertension  requiring drug treatment, left ventricular dysfunction, age >75  years, age between 65-75 years plus diabetes mellitus, or age between  65-75 years plus symptomatic coronary heart disease.


4,576 patients (2,283 in the idraparinux group and 2,293 in the VKA group) have been randomized between September 2003 and July 2005.
Patients (n=4,576) with AF who were eligible for VKA treatment were randomized to receive either subcutaneous idraparinux 2.5 mg once a week (2,283) or VKA therapy (2,293) adjusted to achieve a target [[international normalized ratio]] ([[INR]]) of 2.5 (range 2 to 3) between September 2003 and July 2005. The study was powered to show non-inferior efficacy of idraparinux, compared with standard vitamin K antagonist (VKA) treatment in patients with AF who require prolonged oral anticoagulation. The  primary efficacy endpoint was the composite of all strokes (ischemic, hemorrhagic and undefined) and non-CNS SE within the planned treatment period. The principal safety endpoint  was the occurrence of major bleeding or clinically relevant non-major bleeding. The other safety outcome was all cause mortality.
 
Patients  with AF who were eligible for VKA treatment were randomized to receive either subcutaneous idraparinux 2.5 mg once a week or VKA therapy adjusted to achieve the target international normalized ratio (INR) of 2.5 (range 2 to 3). The study was powered to show non-inferior efficacy of idraparinux, compared with standard vitamin K antagonist (VKA) treatment in patients with AF who require prolonged oral anticoagulation. The  primary efficacy endpoint was the composite of all strokes (ischemic, hemorrhagic and undefined) and non-CNS SE within the planned treatment period. The principal safety endpoint  was the occurrence of major bleeding or clinically relevant non-major bleeding. The other safety outcome was all cause mortality.
A weekly subcutaneous administration of idraparinux was as effective as  warfarin, a Vitamin K Antagonist (VKA), in reducing stroke and non  Central Nervous System (CNS) systemic embolic events in patients with  atrial fibrillation (AF), a population at risk of thromboembolic events  (TE). The results of the AMADEUS study were presented at the XXI ISTH  Congress (International Society on Thrombosis and Haemostasis) in  Geneva.
A weekly subcutaneous administration of idraparinux was as effective as  warfarin, a Vitamin K Antagonist (VKA), in reducing stroke and non  Central Nervous System (CNS) systemic embolic events in patients with  atrial fibrillation (AF), a population at risk of thromboembolic events  (TE). The results of the AMADEUS study were presented at the XXI ISTH  Congress (International Society on Thrombosis and Haemostasis) in  Geneva.


The AMADEUS trial, which enrolled a total of 4,576  patients with atrial fibrillation, met its primary endpoint. The event  rate of the composite endpoint of any strokes (ischemic, hemorrhagic, and undefined) and non-CNS systemic embolism was 0.9% with idraparinux and 1.3% with warfarin (p= 0.007), meeting the criteria for non-inferiority.
The AMADEUS trial met its [[primary endpoint]]. The event  rate of the composite endpoint of any strokes (ischemic, hemorrhagic, and undefined) and non-CNS systemic embolism was 0.9% with idraparinux and 1.3% with warfarin (p= 0.007), meeting the criteria for [[non-inferiority]].


The incidence of clinically relevant bleeding, the primary safety outcome, was significantly higher in the idraparinux  group than in the comparator group (19.7% vs. 11.3%, p<0.0001),  although, overall no difference was observed in the all causes mortality  between the two treatment groups''.'' Bleeding appeared over time and was more pronounced in patients with impaired renal function and in the elderly. These observations indicate  the need to consider a dose reduction of idraparinux depending on these  characteristics in patients with AF. This will be addressed in the new  BOREALIS-AF study that will compare the new neutralizable form of  idraparinux (biotinylated idraparinux) to VKA in patients with atrial  fibrillation and in which the dose will be adjusted depending on age and  renal function after 7 weeks of treatment.
The incidence of clinically relevant bleeding, the primary safety outcome, was significantly higher in the idraparinux  group than in the comparator group (19.7% vs. 11.3%, p<0.0001).  There was an increase in fatal bleeds as well (13/1941 (0.7%) vs 2/2,131 (0.1%), HR =7.14, [95% CI =1.61;31.58],  although, overall no difference was observed in the all causes mortality  between the two treatment groups.  Intracranial hemorrhage was not increased (4/1,922 (0.2%) vs 5/2,107 (0.2%), HR= 0.88, [95% CI = 0.24;3.26]). Bleeding appeared over time and was more pronounced in patients with impaired renal function and in the elderly.


Despite the early  termination of the study due to the imbalance of bleeding events and low  event rates, the trial succeeded in demonstrating the efficacy of idraparinux and met the criteria for non inferiority.With once a week  idraparinux treatment we could have a convenient alternative to the  cumbersome VKA treatment for patients suffering from atrial fibrillation  recurrent complications.”''''  said Professor Harry Büller, from the University of Amsterdam’s  Academic Medical Center Department of Vascular Medicine and principal  investigator of the AMADEUS study. ''''“Nevertheless,  the improvement of the safety profile while preserving efficacy should  be addressed in the new BOREALIS-AF study with the once a week treatment with reversible biotinylated idraparinux, (a big step forward, well  suited for a long acting agent) and dose adjustment according to patients characteristics.”'''' he added.
Given the increased risk of bleeding, future trials will adjust the dose of a reversible form of idraparinux depending on patient age and renal function. The BOREALIS-AF study will evaluate the safety and efficacy of a new neutralizable / reversible form of idraparinux (biotinylated idraparinux) to VKA in patients with atrial fibrillation and the dose will be adjusted depending on age and renal function after 7 weeks of treatment.


===The BOREALIS-AF study===
==Biotinylated Version of Idraparinux==
Because idraparinux has a very long [[half life]], a [[biotinylated]]  version of this drug (SSR 126517) is also in clinical development. The addition of a [[biotin]] moiety to the structure allows the more rapid removal of the drug and reversal upon the addition of [[avidin]]. A bioequipotency study of biotinylated  idraparinux vs. idraparinux for the treatment of [[DVT]] is ongoing.


BOREALIS-AF is a multicenter, [[randomized]], [[double-blind]], assessor-blind, [[non-inferiority]] study comparing the efficacy and safety of once-a-week  subcutaneous biotinylated idraparinux with adjusted-dose [[warfarin]] in the prevention of stroke and systemic thromboembolic events in patients with [[atrial fibrillation]].
Biotinylated idraparinux is being compared to [[warfarin]] for the treatment of [[pulmonary embolism]] in the phase III CASSIOPEA.


Treatment will be administrated for a period of 6 months to 2 years. All patients will start with biotinylated idraparinux 3 mg (equivalent to base idraparinux 2.5 mg) once-a-week for 7 weeks, and then the dose will be  reduced depending on age and renal function.
==The BOREALIS-AF study of Biotinylated Idraparinux==


==Biotinylated Version of Idraparinux==
Once a week idraparinux treatment could represent a convenient alternative to cumbersome VKA treatment for AF patients. The goal of BOREALIS-AF is to improve the safety profile of Idraparinux using the reversible biotinylated idraparinux and adjusting the dose to patients renal function and age.
Because idraparinux has a very long [[half life]], a [[biotinylated]] version of this drug (SSR 126517) is also in clinical development. The addition of a [[biotin]] moiety to the structure allows the more rapid removal of the drug upon the addition of [[avidin]]. A bioequipotency study of biotinylated idraparinux vs. idraparinux for the treatment of [[DVT]] is ongoing.  


Biotinylated idraparinux is being compared to [[warfarin]] for the treatment of [[pulmonary embolism]] in the phase III CASSIOPEA.
BOREALIS-AF is a multicenter, [[randomized]], [[double-blind]], assessor-blind, [[non-inferiority]] study comparing the efficacy and safety of once-a-week subcutaneous biotinylated idraparinux (whichis reversible) with adjusted-dose [[warfarin]] in the prevention of stroke and systemic thromboembolic events in patients with [[atrial fibrillation]].


Treatment  will be administrated for a period of 6 months to 2 years. All patients will start with biotinylated idraparinux 3 mg (equivalent to base  idraparinux 2.5 mg) once-a-week for 7 weeks, and then the dose will be reduced depending on age and renal function.


==Reference==
==References==
{{reflist|2}}
{{reflist|2}}


Line 95: Line 90:
[[Category:Drugs]]
[[Category:Drugs]]
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Heparins]]
[[Category:Oligosaccharides]]


{{WikiDoc Help Menu}}
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
{{WikiDoc Sources}}

Latest revision as of 16:17, 9 August 2012

Idraparinux
Clinical data
Routes of
administration		Subcutaneous
ATC code
  • none
Legal status
Legal status
  • Investigational
Pharmacokinetic data
Elimination half-life80-130 hours
Identifiers
CAS Number
PubChem CID
ChemSpider
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC38H55Na9O49S7
Molar mass1727.17683 g/mol
3D model (JSmol)
  (verify)

WikiDoc Resources for Idraparinux

Articles

Most recent articles on Idraparinux

Most cited articles on Idraparinux

Review articles on Idraparinux

Articles on Idraparinux in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Idraparinux

Images of Idraparinux

Photos of Idraparinux

Podcasts & MP3s on Idraparinux

Videos on Idraparinux

Evidence Based Medicine

Cochrane Collaboration on Idraparinux

Bandolier on Idraparinux

TRIP on Idraparinux

Clinical Trials

Ongoing Trials on Idraparinux at Clinical Trials.gov

Trial results on Idraparinux

Clinical Trials on Idraparinux at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Idraparinux

NICE Guidance on Idraparinux

NHS PRODIGY Guidance

FDA on Idraparinux

CDC on Idraparinux

Books

Books on Idraparinux

News

Idraparinux in the news

Be alerted to news on Idraparinux

News trends on Idraparinux

Commentary

Blogs on Idraparinux

Definitions

Definitions of Idraparinux

Patient Resources / Community

Patient resources on Idraparinux

Discussion groups on Idraparinux

Patient Handouts on Idraparinux

Directions to Hospitals Treating Idraparinux

Risk calculators and risk factors for Idraparinux

Healthcare Provider Resources

Symptoms of Idraparinux

Causes & Risk Factors for Idraparinux

Diagnostic studies for Idraparinux

Treatment of Idraparinux

Continuing Medical Education (CME)

CME Programs on Idraparinux

International

Idraparinux en Espanol

Idraparinux en Francais

Business

Idraparinux in the Marketplace

Patents on Idraparinux

Experimental / Informatics

List of terms related to Idraparinux

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Idraparinux sodium is a novel long-acting synthetic indirect inhibitor of coagulation factor Xa[1]. The agent is being developed by Sanofi-Aventis. It has a similar chemical structure and mechanism of action as fondaparinux, but its elimination half-life of 80 hours is 5 to 6 times longer than that of fondaparix (17 hours). Given its long half life, it can be injected subcutaneously once a week.

Use in Atrial Fibrillation

The AMADEUS study

The phase III AMADEUS study was a randomized, open label trial designed to compare the efficacy and safety of once-a-week idraparinux versus oral VKA treatment for the long-term prevention of thromboembolic events (stroke and non-central nervous system systemic embolism) in patients with AF and at least one additional risk factor for stroke. The predefined risk factors were previous ischemic stroke, transient ischemic attack or SE, hypertension requiring drug treatment, left ventricular dysfunction, age >75 years, age between 65-75 years plus diabetes mellitus, or age between 65-75 years plus symptomatic coronary heart disease.

Patients (n=4,576) with AF who were eligible for VKA treatment were randomized to receive either subcutaneous idraparinux 2.5 mg once a week (2,283) or VKA therapy (2,293) adjusted to achieve a target international normalized ratio (INR) of 2.5 (range 2 to 3) between September 2003 and July 2005. The study was powered to show non-inferior efficacy of idraparinux, compared with standard vitamin K antagonist (VKA) treatment in patients with AF who require prolonged oral anticoagulation. The primary efficacy endpoint was the composite of all strokes (ischemic, hemorrhagic and undefined) and non-CNS SE within the planned treatment period. The principal safety endpoint was the occurrence of major bleeding or clinically relevant non-major bleeding. The other safety outcome was all cause mortality. A weekly subcutaneous administration of idraparinux was as effective as warfarin, a Vitamin K Antagonist (VKA), in reducing stroke and non Central Nervous System (CNS) systemic embolic events in patients with atrial fibrillation (AF), a population at risk of thromboembolic events (TE). The results of the AMADEUS study were presented at the XXI ISTH Congress (International Society on Thrombosis and Haemostasis) in Geneva.

The AMADEUS trial met its primary endpoint. The event rate of the composite endpoint of any strokes (ischemic, hemorrhagic, and undefined) and non-CNS systemic embolism was 0.9% with idraparinux and 1.3% with warfarin (p= 0.007), meeting the criteria for non-inferiority.

The incidence of clinically relevant bleeding, the primary safety outcome, was significantly higher in the idraparinux group than in the comparator group (19.7% vs. 11.3%, p<0.0001). There was an increase in fatal bleeds as well (13/1941 (0.7%) vs 2/2,131 (0.1%), HR =7.14, [95% CI =1.61;31.58], although, overall no difference was observed in the all causes mortality between the two treatment groups. Intracranial hemorrhage was not increased (4/1,922 (0.2%) vs 5/2,107 (0.2%), HR= 0.88, [95% CI = 0.24;3.26]). Bleeding appeared over time and was more pronounced in patients with impaired renal function and in the elderly.

Given the increased risk of bleeding, future trials will adjust the dose of a reversible form of idraparinux depending on patient age and renal function. The BOREALIS-AF study will evaluate the safety and efficacy of a new neutralizable / reversible form of idraparinux (biotinylated idraparinux) to VKA in patients with atrial fibrillation and the dose will be adjusted depending on age and renal function after 7 weeks of treatment.

Biotinylated Version of Idraparinux

Because idraparinux has a very long half life, a biotinylated version of this drug (SSR 126517) is also in clinical development. The addition of a biotin moiety to the structure allows the more rapid removal of the drug and reversal upon the addition of avidin. A bioequipotency study of biotinylated idraparinux vs. idraparinux for the treatment of DVT is ongoing.

Biotinylated idraparinux is being compared to warfarin for the treatment of pulmonary embolism in the phase III CASSIOPEA.

The BOREALIS-AF study of Biotinylated Idraparinux

Once a week idraparinux treatment could represent a convenient alternative to cumbersome VKA treatment for AF patients. The goal of BOREALIS-AF is to improve the safety profile of Idraparinux using the reversible biotinylated idraparinux and adjusting the dose to patients renal function and age.

BOREALIS-AF is a multicenter, randomized, double-blind, assessor-blind, non-inferiority study comparing the efficacy and safety of once-a-week subcutaneous biotinylated idraparinux (whichis reversible) with adjusted-dose warfarin in the prevention of stroke and systemic thromboembolic events in patients with atrial fibrillation.

Treatment will be administrated for a period of 6 months to 2 years. All patients will start with biotinylated idraparinux 3 mg (equivalent to base idraparinux 2.5 mg) once-a-week for 7 weeks, and then the dose will be reduced depending on age and renal function.

References

  1. ↑ Bousser MG, Bouthier J, Büller HR; et al. (2008). "Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial". Lancet. 371 (9609): 315–21. doi:10.1016/S0140-6736(08)60168-3. PMID 18294998. Unknown parameter |month= ignored (help)


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Idraparinux&oldid=677061"