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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00790907

First received: November 13, 2008

Last updated: June 14, 2012

Last verified: June 2011

History of Changes

Results First Received: May 10, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	Unstable Angina Non ST Segment Elevation Myocardial Infarction
Interventions:	Drug: fondaparinux background and standard dose UFH Drug: Fondaparinux background and low dose heparin Drug: Open label fondaparinux

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants (par.) received open-label (OL) fondaparinux (fond.). Par. indicated for percutaneous coronary intervention (PCI) were randomized to low- or standard-dose unfractionated heparin during PCI. Post-PCI, par. could resume OL fond. Par. not indicated for PCI weren’t randomized and continued OL fond.

Reporting Groups

	Description
Open-label Fondaparinux 2.5 mg	Open-label (OL) fondaparinux syringes pre-filled with 2.5 milligrams (mg), administered subcutaneously (s.c.) once daily for up to 8 days or hospital discharge, whichever was earlier, for those participants not indicated for percutaneous coronary intervention (PCI) and not randomized
OL Fondaparinux Background + Low Dose UFH During PCI	OL 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 unfractionated heparin (UFH) (50 units/kilogram [U/kg], which was not adjusted for planned glycoprotein [GP] IIb/IIIa use or activated clotting time [ACT]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) may have been considered for randomization.
OL Fondaparinux Background + Standard Dose UFH During PCI	OL 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 GPIIb/IIIa inhibitor use: 60 U/kg; no planned use: 85 U/kg and adjusted based on 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.

Participant Flow: Overall Study

	Open-label Fondaparinux 2.5 mg	OL Fondaparinux Background + Low Dose UFH During PCI	OL Fondaparinux Background + Standard Dose UFH During PCI
STARTED	1209	1024	1002
COMPLETED	754	684	663
NOT COMPLETED	455	340	339
Adverse Event	9	7	6
Physician Decision	304	271	255
Withdrawal by Subject	1	7	5
Bleeding Event	11	16	21
Required Protocol-prohibited Therapy	17	5	7
Qualifying Condition Not Present	29	14	16
Verbatim Reason on the Case Report Form	74	20	29
Did Not Receive Study Drug	10	0	0

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Open-label Fondaparinux 2.5 mg	Open-label (OL) fondaparinux syringes pre-filled with 2.5 milligrams (mg), administered subcutaneously (s.c.) once daily for up to 8 days or hospital discharge, whichever was earlier, for those participants not indicated for percutaneous coronary intervention (PCI) and not randomized
OL Fondaparinux Background + Low Dose UFH During PCI	OL 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 unfractionated heparin (UFH) (50 units/kilogram [U/kg], which was not adjusted for planned glycoprotein [GP] IIb/IIIa use or activated clotting time [ACT]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) may have been considered for randomization.
OL Fondaparinux Background + Standard Dose UFH During PCI	OL 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 GPIIb/IIIa inhibitor use: 60 U/kg; no planned use: 85 U/kg and adjusted based on 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.
Total	Total of all reporting groups

Baseline Measures

	Open-label Fondaparinux 2.5 mg	OL Fondaparinux Background + Low Dose UFH During PCI	OL Fondaparinux Background + Standard Dose UFH During PCI	Total
Number of Participants [units: participants]	1209	1024	1002	3235
Age [units: Years] Mean ± Standard Deviation	65.8 ± 11.07	65.3 ± 11.25	65.5 ± 11.10	65.5 ± 11.14
Gender [units: Participants]
Female	486	335	316	1137
Male	723	689	686	2098
Race/Ethnicity, Customized ^[1] [units: participants]
South Asian	249	151	150	550
Other Asian	63	61	61	185
Arab	3	5	3	11
Black African	4	1	3	8
European	830	768	749	2347
Native Latin	57	37	33	127
Other - verbatim reason collected on the CRF	2	1	2	5
Missing	1	0	1	2

[1]	CRF, case report form.

Outcome Measures

Show All Outcome Measures

1. Primary:

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) ]

Show Outcome Measure 1

2. Secondary:

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 ]

Show Outcome Measure 2

3. Secondary:

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) ]

Show Outcome Measure 3

4. Secondary:

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) ]

Show Outcome Measure 4

5. Secondary:

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) ]

Show Outcome Measure 5

6. Secondary:

Number of Participants With Major PCI-related Procedural Complications [ Time Frame: During PCI procedure: immediately after randomization (approximately 10-75 minutes) ]

Hide Outcome Measure 6

Measure Type	Secondary
Measure Title	Number of Participants With Major PCI-related Procedural Complications
Measure Description	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.
Time Frame	During PCI procedure: immediately after randomization (approximately 10-75 minutes)
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups

	Description
OL Fondaparinux Background + Low Dose UFH During PCI	OL 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 unfractionated heparin (UFH) (50 units/kilogram [U/kg], which was not adjusted for planned glycoprotein [GP] IIb/IIIa use or activated clotting time [ACT]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) may have been considered for randomization.
OL Fondaparinux Background + Standard Dose UFH During PCI	OL 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 GPIIb/IIIa inhibitor use: 60 U/kg; no planned use: 85 U/kg and adjusted based on 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.

Description

OL Fondaparinux Background + Low Dose UFH During PCI

OL 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 unfractionated heparin (UFH) (50 units/kilogram [U/kg], which was not adjusted for planned glycoprotein [GP] IIb/IIIa use or activated clotting time [ACT]). Participants who presented in the catheterization laboratory and who were receiving commercially available fondaparinux prescribed for the initial treatment of unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) may have been considered for randomization.

OL Fondaparinux Background + Standard Dose UFH During PCI

OL 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 GPIIb/IIIa inhibitor use: 60 U/kg; no planned use: 85 U/kg and adjusted based on 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.

Measured Values

	OL Fondaparinux Background + Low Dose UFH During PCI	OL Fondaparinux Background + Standard Dose UFH During PCI
Number of Participants Analyzed [units: participants]	1024	1002
Number of Participants With Major PCI-related Procedural Complications [units: participants]
Abrupt Vessel Closure	10	17
New Angiographic Thrombus	11	8
Suspected Catheter-related Thrombus	4	3
Catheter-related Thrombus-Adjudicated	4	1
No-reflow Phenomenon	20	22
New Major Dissection with Reduced Flow	10	10

No statistical analysis provided for Number of Participants With Major PCI-related Procedural Complications

7. Secondary:

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 ]

Show Outcome Measure 7

8. 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 [ 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 ]

Show Outcome Measure 8

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

Publications of Results:

The FUTURA/OASIS-8 Trial Group. 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; 304(12):1339-1349.

Publications automatically indexed to this study:

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.

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. Epub 2010 Aug 31.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00790907 History of Changes
Other Study ID Numbers:	108888
Study First Received:	November 13, 2008
Results First Received:	May 10, 2011
Last Updated:	June 14, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare United Kingdom: Medicines and Healthcare Products Regulatory Agency Argentina: Ministry of Health - A.N.M.A.T Brazil: ANVISA Russia: Russian Ministry of Health Canada: Health Canada India: Drugs Controlle Gerneral of India South Korea: Food and Drug Administration United States: Food and Drug Administration Europe: European Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

To Top