Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS)

NCT ID: NCT00790907

Last Updated: 2017-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 3235 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2010-05-31

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.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Open label fondaparinux background and standard dose UFH

Subjects indicated for PCI and randomized to receive standard dose UFH

Group Type: EXPERIMENTAL

fondaparinux background and standard dose UFH

Intervention Type: DRUG

Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded standard dose UFH (based on planned glycoprotein \[GP\] IIb/IIIa inhibitor use: 60 units/kilogram (U/kg); no planned use: 85 U/kg and adjusted based on activated clotting time (ACT) \[maximum two additional bolus doses\]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.

Open label fondaparinux background and low dose UFH

Subjects indicated for PCI and randomized to receive low dose UFH

Group Type: EXPERIMENTAL

Fondaparinux background and low dose heparin

Intervention Type: DRUG

Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded low-dose UFH (50 U/kg), which was not adjusted for planned GPIIb/IIIa inhibitor use or ACT). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.

Open label fondapaparinux

Subjects not indicated for PCI and not randomized

Group Type: OTHER

Open label fondaparinux

Intervention Type: DRUG

Open-label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier, for those participants not indicated for PCI and not randomized

Interventions

fondaparinux background and standard dose UFH

Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded standard dose UFH (based on planned glycoprotein \[GP\] IIb/IIIa inhibitor use: 60 units/kilogram (U/kg); no planned use: 85 U/kg and adjusted based on activated clotting time (ACT) \[maximum two additional bolus doses\]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.

Intervention Type: DRUG

Fondaparinux background and low dose heparin

Open label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier. Participants indicated for PCI were randomized to receive adjunctive blinded low-dose UFH (50 U/kg), which was not adjusted for planned GPIIb/IIIa inhibitor use or ACT). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of UA/NSTEMI may have been considered for randomization.

Intervention Type: DRUG

Open label fondaparinux

Open-label fondaparinux syringes pre-filled with 2.5 mg, administered s.c. once daily for up to 8 days or hospital discharge, whichever was earlier, for those participants not indicated for PCI and not randomized

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Ocala, Florida, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

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Syracuse, New York, United States

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Dallas, Texas, United States

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Adrogué, Buenos Aires, Argentina

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Bahía Blanca, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Merlo, Buenos Aires, Argentina

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Quilmes, Buenos Aires, Argentina

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Quilmes, Buenos Aires, Argentina

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Rosario, Buenos Aires, Argentina

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Corrientes, Corrientes Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Santa Fe, Santa Fe Province, Argentina

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Santa Fe, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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San Miguel de Tucumán, , Argentina

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Campina Grande do Sul, Paraná, Brazil

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Curitiba, Paraná, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Blumenau, Santa Catarina, Brazil

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Campinas, São Paulo, Brazil

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Marília, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Calgary, Alberta, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Karlovy Vary, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Ústí nad Labem, , Czechia

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Zlín, , Czechia

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Besançon, , France

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Caen, , France

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Créteil, , France

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Dijon, , France

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Marseille, , France

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Montfermeil, , France

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Paris, , France

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Rouen, , France

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Toulouse, , France

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Tours, , France

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Heidelberg, Baden-Wurttemberg, Germany

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Heidenheim, Baden-Wurttemberg, Germany

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Bad Tölz, Bavaria, Germany

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Dachau, Bavaria, Germany

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Erlangen, Bavaria, Germany

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Simbach A. Inn, Bavaria, Germany

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Bernau bei Berlin, Brandenburg, Germany

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Cottbus, Brandenburg, Germany

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Bremen, City state Bremen, Germany

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Hamburg, City state of Hamburg, Germany

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Hamburg, City state of Hamburg, Germany

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Kassel, Hesse, Germany

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Langen, Hesse, Germany

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Rüsselsheim am Main, Hesse, Germany

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Bad Rothenfelde, Lower Saxony, Germany

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Göttingen, Lower Saxony, Germany

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Rostock, Mecklenburg-Vorpommern, Germany

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Bonn, North Rhine-Westphalia, Germany

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Cologne, North Rhine-Westphalia, Germany

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Herford, North Rhine-Westphalia, Germany

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Mönchengladbach, North Rhine-Westphalia, Germany

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Neuss, North Rhine-Westphalia, Germany

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Witten, North Rhine-Westphalia, Germany

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Mainz, Rhineland-Palatinate, Germany

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Homburg, Saarland, Germany

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Dresden, Saxony, Germany

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Leipzig, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Quedlinburg, Saxony-Anhalt, Germany

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Lübeck, Schleswig-Holstein, Germany

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Neumünster, Schleswig-Holstein, Germany

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Berlin, State of Berlin, Germany

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Berlin, State of Berlin, Germany

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Berlin, State of Berlin, Germany

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Erfurt, Thuringia, Germany

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Ioannina, , Greece

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Rio- Patras, , Greece

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Balatonfüred, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Miskolc, , Hungary

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Pécs, , Hungary

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Zalaegerszeg, , Hungary

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Ahmedabad, , India

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Ahmedabad, , India

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Ahmedabad, , India

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Bandra, Mumbai, , India

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Bangalore, , India

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Dhantoli, Nagpur, , India

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Dhantoli, Nagpur, , India

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Jaipur, , India

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Lucknow, , India

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New Delhi, , India

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New Delhi, , India

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Pune, , India

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Pune, , India

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Secunderabad, , India

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Vadodara, , India

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Bologna, Emilia-Romagna, Italy

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Ferrara, Emilia-Romagna, Italy

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Udine, Friuli Venezia Giulia, Italy

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Cremona, Lombardy, Italy

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Mantova, Lombardy, Italy

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Milan, Lombardy, Italy

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Pavia, Lombardy, Italy

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Rozzano (Mi), Lombardy, Italy

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Novara, Piedmont, Italy

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Sassari, Sardinia, Italy

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Lucca, Tuscany, Italy

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Perugia, Umbria, Italy

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Eindhoven, , Netherlands

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Nieuwegein, , Netherlands

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Rotterdam, , Netherlands

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Bialystok, , Poland

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Bytom, , Poland

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Częstochowa, , Poland

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Dąbrowa Górnicza, , Poland

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Gdansk, , Poland

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Gdynia, , Poland

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Koszalin, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Lubin, , Poland

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Radom, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wałbrzych, , Poland

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Wroclaw, , Poland

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Włocławek, , Poland

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Barnaul, , Russia

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Kemerovo, , Russia

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Krasnodar, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Perm, , Russia

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Saint Petersburg, , Russia

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St'Petersburg, , Russia

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Tomsk, , Russia

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Voronezh, , Russia

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Yaroslavl, , Russia

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Busan, , South Korea

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Daejeon, , South Korea

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Gangnam-gu, Seoul, , South Korea

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Goyang-si, Gyeonggi-do, , South Korea

GSK Investigational Site

Gwangju, , South Korea

GSK Investigational Site

Gwangju, , South Korea

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Gyeonggi-do, , South Korea

GSK Investigational Site

Jeonju-si, Jeollabuk-Do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Galdakao, , Spain

GSK Investigational Site

León, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

GSK Investigational Site

Málaga, , Spain

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Oviedo, , Spain

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Palma de Mallorca, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Vigo/Pontevedra, , Spain

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Birmingham, , United Kingdom

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Bristol, , United Kingdom

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Dundee, , United Kingdom

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Edinburgh, , United Kingdom

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Southampton, , United Kingdom

GSK Investigational Site

Tooting, London, , United Kingdom

Countries

United States; Argentina; Brazil; Bulgaria; Canada; Czechia; France; Germany; Greece; Hungary; India; Italy; Netherlands; Poland; Russia; South Korea; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 20805623 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25873729 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21146654 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

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Document Type: Individual Participant Data Set

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Document Type: Informed Consent Form

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Document Type: Study Protocol

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Document Type: Annotated Case Report Form

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Document Type: Dataset Specification

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Document Type: Statistical Analysis Plan

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Other Identifiers

108888

Identifier Type: -

Identifier Source: org_study_id