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

Acute Coronary Syndrome Clinical Trial

— FUTURA/OASIS 8  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00790907
• Other study ID #: 108888
• Status: Completed
• Phase: Phase 4
• First received: November 13, 2008
• Last updated: March 21, 2017
• Start date: February 2009
• Est. completion date: May 2010

Study information

• Verified date: March 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3235
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Myocardial Infarction
• Syndrome

Intervention

Drug:
• 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.
• 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.
• 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

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Adrogue	Buenos Aires
Argentina	GSK Investigational Site	Bahia Blanca	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Corrientes
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Merlo	Buenos Aires
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán
Argentina	GSK Investigational Site	Santa Fe
Argentina	GSK Investigational Site	Santa Fe
Brazil	GSK Investigational Site	Blumenau	Santa Catarina
Brazil	GSK Investigational Site	Campina Grande do Sul	Paraná
Brazil	GSK Investigational Site	Campinas	São Paulo
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Marília	São Paulo
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	São José do Rio Preto	São Paulo
Brazil	GSK Investigational Site	São José do Rio Preto	São Paulo
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Chicoutimi	Quebec
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Hradec Kralove
Czech Republic	GSK Investigational Site	Karlovy Vary
Czech Republic	GSK Investigational Site	Plzen
Czech Republic	GSK Investigational Site	Praha 10
Czech Republic	GSK Investigational Site	Praha 2
Czech Republic	GSK Investigational Site	Praha 5
Czech Republic	GSK Investigational Site	Usti nad Labem
Czech Republic	GSK Investigational Site	Zlin
France	GSK Investigational Site	Besançon Cedex
France	GSK Investigational Site	Caen Cedex 9
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Marseille Cedex 05
France	GSK Investigational Site	Montfermeil
France	GSK Investigational Site	Paris Cedex 18
France	GSK Investigational Site	Rouen Cedex
France	GSK Investigational Site	Toulouse cedex 9
France	GSK Investigational Site	Tours cedex 09
Germany	GSK Investigational Site	Bad Rothenfelde	Niedersachsen
Germany	GSK Investigational Site	Bad Toelz	Bayern
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bernau	Brandenburg
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bremen
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Dachau	Bayern
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Erfurt	Thueringen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Heidenheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Herford	Nordrhein-Westfalen
Germany	GSK Investigational Site	Homburg	Saarland
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Langen	Hessen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Moenchengladbach	Nordrhein-Westfalen
Germany	GSK Investigational Site	Neumuenster	Schleswig-Holstein
Germany	GSK Investigational Site	Neuss	Nordrhein-Westfalen
Germany	GSK Investigational Site	Quedlinburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Rostock	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Ruesselsheim	Hessen
Germany	GSK Investigational Site	Simbach a. Inn	Bayern
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Rio- Patras
Hungary	GSK Investigational Site	Balatonfüred
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Miskolc
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Zalaegerszeg
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Bandra, Mumbai
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Dhantoli, Nagpur
India	GSK Investigational Site	Dhantoli, Nagpur
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Secunderabad
India	GSK Investigational Site	Vadodara
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Cremona	Lombardia
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Lucca	Toscana
Italy	GSK Investigational Site	Mantova	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Novara	Piemonte
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Perugia	Umbria
Italy	GSK Investigational Site	Rozzano (Mi)	Lombardia
Italy	GSK Investigational Site	Sassari	Sardegna
Italy	GSK Investigational Site	Udine	Friuli-Venezia-Giulia
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Gangnam-gu, Seoul
Korea, Republic of	GSK Investigational Site	Goyang-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	jeonju-si, Jeollabuk-Do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Nieuwegein
Netherlands	GSK Investigational Site	Rotterdam
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bytom
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Dabrowa Gornicza
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdynia
Poland	GSK Investigational Site	Koszalin
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lubin
Poland	GSK Investigational Site	Radom
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Walbrzych
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wloclawek
Poland	GSK Investigational Site	Wroclaw
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
Spain	GSK Investigational Site	Alicante
Spain	GSK Investigational Site	Galdakao
Spain	GSK Investigational Site	León
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Vigo/Pontevedra
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Dundee
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Southampton
United Kingdom	GSK Investigational Site	Tooting, London
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Czech Republic,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

References & Publications (1)

FUTURA/OASIS-8 Trial Group., Steg PG, Jolly SS, Mehta SR, Afzal R, Xavier D, Rupprecht HJ, López-Sendón 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Composite of Major Bleeding, Minor Bleeding, or Major Vascular Access Site Complications During the Peri-PCI Period	The peri-percutaneous coronary intervention (peri-PCI) period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major and minor bleeding events were adjudicated by a blinded central independent adjudication committee (CIAC). Major vascular access site complications comprised large hematoma, pseudoaneurysm requiring treatment, aterio-venous fistula, or other vascular procedures related to the access site.	Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
Secondary	Number of Participants With Composite of Major Bleeding During the Peri-PCI Period, With Death, MI, or TVR at Day 30	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of death, myocardial infarction (MI) and target vessel revascularisation (TVR) was performed at Day 30. Major bleeding, MI and TVR were adjudicated by a blinded CIAC.	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
Secondary	Number of Participants With Major Bleeding During the Peri-PCI Period	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major bleeding, MI and TVR were adjudicated by a blinded CIAC.	Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
Secondary	Number of Participants With Minor Bleeding During the Peri-PCI Period	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Minor bleeding events were adjudicated by a blinded CIAC.	Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
Secondary	Number of Participants With Major Vascular Access Site Complications During the Peri-PCI Period	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Major vascular access site complications included: large hematoma, pseudoaneurysm requiring treatment, arterio-venous fistula, or other vascular procedures related to the access site.	Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total)
Secondary	Number of Participants With Major PCI-related Procedural Complications	Major PCI-related procedural complications included: abrupt vessel closure, a new angiographic filling defect representing either angiographic thrombus or major dissection with reduced flow, no-reflow phenomenon, or catheter-related thrombus. Investigator reports of catheter-related thrombus were defined as suspected catheter-related thrombus events, and were adjudicated by a blinded CIAC.	During PCI procedure: immediately after randomization (approximately 10-75 minutes)
Secondary	Number of Participants With Composite of Death, MI or TVR During the Peri-PCI Period and at Day 30	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of composite of death, MI, or TVR was performed both during the peri-PCI period and at Day 30. MI and TVR events were adjudicated by a blinded CIAC.	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
Secondary	Number of Participants Experiencing Death, MI, TVR, Definite/Probable Stent Thrombosis, or Stroke, Assessed Separately During the Peri-PCI Period and at Day 30	The peri-PCI period was defined as the period during the time from randomization up to 48 hours after the end of the PCI procedure, typically 49 hours total. Assessment of death, MI, TVR, definite/probable stent thrombosis, or stroke was performed during the peri-PCI period and at Day 30. MI, TVR, definite/probable stent thrombosis, and stroke events were adjudicated by a blinded CIAC.	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

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