Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS) (FUTURA/OASIS 8)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00790907
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : June 7, 2011
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE November 13, 2008
First Posted Date  ICMJE November 14, 2008
Results First Submitted Date  ICMJE May 10, 2011
Results First Posted Date  ICMJE June 7, 2011
Last Update Posted Date March 23, 2017
Study Start Date  ICMJE February 2009
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2011)
Number of Participants With Composite of Major Bleeding, Minor Bleeding, or Major Vascular Access Site Complications During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
Composite of major bleeding, minor bleeding or major vascular access site complications [ Time Frame: Time of randomization up to 48 hours post PCI procedure ]
Change History Complete list of historical versions of study NCT00790907 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2011)
  • Number of Participants With Composite of Major Bleeding During the Peri-PCI Period, With Death, MI, or TVR at Day 30 [ Time Frame: 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 ]
    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.
  • Number of Participants With Major Bleeding During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ]
    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.
  • Number of Participants With Minor Bleeding During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ]
    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.
  • Number of Participants With Major Vascular Access Site Complications During the Peri-PCI Period [ Time Frame: Peri-PCI Period: occurred at randomization (from randomization to 48 hours after end of PCI procedure, typically 49 hours total) ]
    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.
  • Number of Participants With Major PCI-related Procedural Complications [ Time Frame: During PCI procedure: immediately after randomization (approximately 10-75 minutes) ]
    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.
  • Number of Participants With Composite of Death, MI or TVR During the Peri-PCI Period and at Day 30 [ Time Frame: 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 ]
    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.
  • Number of Participants Experiencing Death, MI, TVR, Definite/Probable Stent Thrombosis, or Stroke, Assessed Separately During the Peri-PCI Period and at Day 30 [ Time Frame: 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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2008)
  • Composite of major bleeding with death, MI or target vessel revascularization [ Time Frame: Major bleeding from randomisation until 48 hours post PCI; Death, MI or target vessel revascularisation at Day 30 ]
  • Major bleeding, minor bleeding assessed separately [ Time Frame: Over the course of the study ]
  • Major vascular access site complications [ Time Frame: Over the course of the study ]
  • Composite of death, MI, target vessel revascularization plus the components assessed separately [ Time Frame: Over the course of the study ]
  • Stroke [ Time Frame: Over the course of the study ]
  • Definite and probable stent thrombosis [ Time Frame: Over the course of the study ]
  • Major PCI-related procedural complications [ Time Frame: Randomization until 48 hours following PCI ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fondaparinux Trial With Unfractionated Heparin (UFH) During Revascularization in Acute Coronary Syndromes (ACS)
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Acute Coronary Syndrome
Intervention  ICMJE
  • 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.
  • 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.
  • 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
Study Arms  ICMJE
  • Experimental: Open label fondaparinux background and standard dose UFH
    Subjects indicated for PCI and randomized to receive standard dose UFH
    Intervention: Drug: fondaparinux background and standard dose UFH
  • Experimental: Open label fondaparinux background and low dose UFH
    Subjects indicated for PCI and randomized to receive low dose UFH
    Intervention: Drug: Fondaparinux background and low dose heparin
  • Open label fondapaparinux
    Subjects not indicated for PCI and not randomized
    Intervention: Drug: Open label fondaparinux
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 6, 2010)
3235
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2008)
4000
Actual Study Completion Date  ICMJE May 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Greece,   Hungary,   India,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00790907
Other Study ID Numbers  ICMJE 108888
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP