Clinical trial NCT00790907: Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS)
Official title: FondaparinUx Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS) (FUTURA). A Prospective Study Evaluating the Safety of Two Regimens of Adjunctive Intravenous UFH During PCI in High Risk Patients With Unstable Angina/Non ST Segment Elevation Myocardial Infarction (UA/NSTEMI) Initially Treated With Subcutaneous Fondaparinux and Referred for Early Coronary Angiography (OASIS 8)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: Unstable angina
Non ST elevation myocardial infarction
PCI
unfractionated heparin
fondaparinux
acute coronary syndrome
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-11-14
Enrollment: 3235
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the safety of two different dose regimens of unfractionated heparin (UFH) during a percutaneous coronary intervention (PCI) procedure in patients with UA (unstable angina)/NSTEMI (non ST segment elevation myocardial infarction) who have been initially treated with fondaparinux.

Detailed description: Subjects presenting at hospital with suspected UA or NSTEMI and who are likely to undergo angiography (ideally within 72 hours) will be assessed for eligibility and consented. Suitable subjects will be enrolled and commence treatment with open-label fondaparinux, 2.5 milligram (mg), subcutaneous (s.c.), once daily. Following angiography subjects indicated for PCI and meeting the additional requirements for randomization will be randomised to receive one of two dose regimens of UFH either standard dose or low dose immediately prior to the PCI procedure. Post-PCI, therapy with fondaparinux (2.5 mg, s.c.) may be resumed at the investigator's discretion for up to a maximum of 8 days or hospital discharge, whichever is earlier.

Subjects not indicated for PCI, will continue treatment with fondaparinux, 2.5mg, s.c, once daily for up to 8 days or hospital discharge, whichever is earlier.

All subjects will be followed up for 30 days after randomization/angiography.

Eligibility criteria: The following are inclusion and exclusion criteria for enrollment in the study:

Inclusion Criteria:

* Presenting or admitted to hospital with symptoms suspected to represent UA or NSTEMI, i.e., clinical history consistent with new onset, or a worsening pattern of, characteristic ischemic chest pain or ischemic symptoms occurring at rest or with minimal activity (lasting longer than 5 minutes or requiring sublingual nitro-glycerine for relief of the pain).
* Available to be enrolled within 48 hours of the onset of the most recent episode of symptoms.
* Planned coronary angiography, with PCI if indicated, within 72 hours of enrollment where possible.
* At least two of the three following additional criteria:
* Age greater than or equal to 60 years
* Troponin T or I or CK-MB above the upper limit of normal for the local institution;
* Electrocardiogram (ECG) changes compatible with ischemia, i.e., ST depression at least 1 mm in 2 contiguous leads or T wave inversion \> 3 mm or any dynamic ST shift or transient ST elevation.
* Written informed consent dated and signed

Exclusion Criteria:

* Age \< 21 years.
* Any contraindication to UFH or fondaparinux
* Contraindication for angiography or PCI at baseline
* Subjects requiring urgent (\<120 minutes) coronary angiography as characterized by those with:
* refractory or recurrent angina associated with dynamic ST-deviation
* heart failure
* life-threatening arrhythmias
* hemodynamic instability
* Subjects already receiving treatment with enoxaparin (or other LMWH), bivalirudin or UFH for treatment of the qualifying events unless the last administered (intravenous(i.v.) or s.c.) dose was:
* ≥ 8 hours for low molecular weight heparin (LMWH)
* ≥60 minutes for bivalirudin
* ≥90 minutes for unfractionated heparin (UFH)
* Hemorrhagic stroke within the last 12 months.
* Indication for anti-coagulation other than acute coronary syndrome (ACS) during the index hospitalization.
* Pregnancy or women of childbearing potential who are not using an effective method of contraception.
* Co-morbid condition with life expectancy less than 6 months.
* Currently receiving an experimental pharmacological agent.
* Revascularization procedure already performed for the qualifying event.
* Severe renal insufficiency (i.e., estimated creatinine clearance \<20 ml/min)

Following angiography and confirmation that the subject is to undergo PCI, the subject must also meet all of the following additional criteria in order to be randomised:

* Subjects will have received at least 1 dose of open-label fondaparinux
* The most recent dose of open-label fondaparinux will not have been more than 24 hours before the start of the PCI procedure.

Primary outcomes:
measure: Number of Participants With Composite of Major Bleeding, Minor Bleeding, or Major Vascular Access Site Complications During the Peri-PCI Period
timeFrame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
Secondary outcomes:
measure: Number of Participants With Composite of Major Bleeding During the Peri-PCI Period, With Death, MI, or TVR at Day 30
timeFrame: Peri-PCI period for major bleeding (during the time from randomization up to 48 hours after the end of PCI [typically 49 hours total] ) and from randomization up to Day 30 for death, MI, or TVR
measure: Number of Participants With Major Bleeding During the Peri-PCI Period
timeFrame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
measure: Number of Participants With Minor Bleeding During the Peri-PCI Period
timeFrame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
measure: Number of Participants With Major Vascular Access Site Complications During the Peri-PCI Period
timeFrame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
measure: Number of Participants With Major PCI-related Procedural Complications
timeFrame: During PCI procedure: immediately after randomization (approximately 10-75 minutes)
measure: Number of Participants With Composite of Death, MI or TVR During the Peri-PCI Period and at Day 30
timeFrame: Peri-PCI (during the time from randomization up to 48 hours after the end of PCI, typically 49 hours total) and from randomization up to Day 30
measure: Number of Participants Experiencing Death, MI, TVR, Definite/Probable Stent Thrombosis, or Stroke, Assessed Separately During the Peri-PCI Period and at Day 30
timeFrame: Peri-PCI (during the time from randomization up to 48 hours after the end of PCI, typically 49 hours total) and from randomization up to Day 30
Other outcomes:
Locations:
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country: United States
facility: GSK Investigational Site
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city: Albuquerque
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state: New Mexico
city: Syracuse
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city: Rosario
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state: São Paulo
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city: Sofia
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city: London
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city: Toronto
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city: Montreal
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state: Quebec
city: Montreal
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state: Quebec
city: Montreal
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state: Quebec
city: Quebec City
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state: Quebec
city: Brno
country: Czech Republic
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city: Hradec Kralove
country: Czech Republic
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city: Karlovy Vary
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city: Plzen
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city: Praha 10
country: Czech Republic
facility: GSK Investigational Site
city: Praha 2
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city: Praha 5
country: Czech Republic
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city: Usti nad Labem
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city: Besançon Cedex
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city: Dijon
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city: Paris Cedex 18
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facility: GSK Investigational Site
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city: Toulouse cedex 9
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city: Tours cedex 09
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facility: GSK Investigational Site
city: Heidelberg
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facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Heidenheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Bad Toelz
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Dachau
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Erlangen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Simbach a. Inn
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bernau
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Cottbus
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Kassel
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facility: GSK Investigational Site
state: Hessen
city: Langen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Ruesselsheim
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Rostock
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Bad Rothenfelde
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Goettingen
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bonn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Herford
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
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facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Moenchengladbach
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facility: GSK Investigational Site
state: Nordrhein-Westfalen
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facility: GSK Investigational Site
state: Nordrhein-Westfalen
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state: Nordrhein-Westfalen
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country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Homburg
country: Germany
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state: Saarland
city: Halle
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Quedlinburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Neumuenster
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Erfurt
country: Germany
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state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
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city: Berlin
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facility: GSK Investigational Site
city: Bremen
country: Germany
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city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
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city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
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city: Ioannina
country: Greece
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city: Budapest
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country: India
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city: Dhantoli, Nagpur
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city: Lucknow
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city: New Delhi
country: India
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country: India
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country: India
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country: Italy
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facility: GSK Investigational Site
state: Emilia-Romagna
city: Udine
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Cremona
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Mantova
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Pavia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Rozzano (Mi)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Novara
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Sassari
country: Italy
facility: GSK Investigational Site
state: Sardegna
city: Lucca
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Busan
country: Korea, Republic of
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city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Gangnam-gu, Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: jeonju-si, Jeollabuk-Do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
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city: Nieuwegein
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bytom
country: Poland
facility: GSK Investigational Site
city: Czestochowa
country: Poland
facility: GSK Investigational Site
city: Dabrowa Gornicza
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
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city: Gdynia
country: Poland
facility: GSK Investigational Site
city: Koszalin
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lubin
country: Poland
facility: GSK Investigational Site
city: Radom
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Walbrzych
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wloclawek
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
country: Russian Federation
facility: GSK Investigational Site
city: Perm
country: Russian Federation
facility: GSK Investigational Site
city: St'Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Galdakao
country: Spain
facility: GSK Investigational Site
city: León
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Palma de Mallorca
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Vigo/Pontevedra
country: Spain
facility: GSK Investigational Site
city: Birmingham
country: United Kingdom
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Dundee
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
city: Tooting, London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: FUTURA/OASIS-8 Trial Group; Steg PG, Jolly SS, Mehta SR, Afzal R, Xavier D, Rupprecht HJ, Lopez-Sendon JL, Budaj A, Diaz R, Avezum A, Widimsky P, Rao SV, Chrolavicius S, Meeks B, Joyner C, Pogue J, Yusuf S. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA. 2010 Sep 22;304(12):1339-49. doi: 10.1001/jama.2010.1320. Epub 2010 Aug 31.
citation: Ducrocq G, Jolly S, Mehta SR, Rao SV, Patel T, Moreno R, Gao P, Steg PG. Activated clotting time and outcomes during percutaneous coronary intervention for non-ST-segment-elevation myocardial infarction: insights from the FUTURA/OASIS-8 Trial. Circ Cardiovasc Interv. 2015 Apr;8(4):e002044. doi: 10.1161/CIRCINTERVENTIONS.114.002044.
citation: Steg PG, Mehta S, Jolly S, Xavier D, Rupprecht HJ, Lopez-Sendon JL, Chrolavicius S, Rao SV, Granger CB, Pogue J, Laing S, Yusuf S. Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): a randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. Am Heart J. 2010 Dec;160(6):1029-34, 1034.e1. doi: 10.1016/j.ahj.2010.07.037.