Atrial FibrillationPhase 2NCT00504556

A Study to Assess the Safety of a Potential New Drug in Comparison to the Standard Practice of Dosing With Warfarin for Non-valvular Atrial Fibrillation

A Phase 2 study testing Edoxaban (DU-176b) and warfarin in people with Atrial Fibrillation and Thromboembolism, run by Daiichi Sankyo at 91 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This study is to assess the safety of a potential new drug DU-176b for the prevention of stroke/systemic embolic event (SEE) in individuals with non-valvular atrial fibrillation (AF). The duration is 3 months of treatment and a 30 day follow-up visit. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Atrial Fibrillation, Thromboembolism
What is being tested?: Edoxaban (DU-176b) and warfarin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,146 participants
Where: 91 sitesin 12 countries
Study dates: Jun 2007to Jun 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, 18 to 80 years old.
Able to provide written informed consent.
Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2

Who cannot join

Subjects with mitral valve disease or previous valvular heart surgery
Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
Known or suspected hereditary or acquired bleeding or coagulation disorder

Trial locations and contacts

91 sites in 12 countries.

Country

City, postcode or hospital

91 sites in 12 countries

Russia24 sites

Study site
Arkhangelsk
Study site
Barnaul
Study site
Chelyabinsk
Study site
Ivanovo
Study site
Kaliningrad
Study site
Kazan'
Study site
Kemerovo
Study site
Krasnodar
Study site
Krasnoyarsk
Study site
Moscow
Study site
N.Novgorod
Study site
Novosibirsk
Study site
Orenburg
Study site
Penza
Study site
Perm
Study site
Rostov-on-Don
Study site
Saint Petersburg
Study site
Samara
Study site
Saratov
Study site
Tomsk
Study site
Tula
Study site
Tyumen
Study site
Volgograd
Study site
Yaroslavl

Other trials in Russia

United States22 sites

Study site
Albany, New York
Study site
Allentown, Pennsylvania
Study site
Anaheim, California
Study site
Atlanta, Georgia
Study site
Bellevue, Washington
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Beverly Hills, California
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Cadillac, Michigan
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Canton, Georgia
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Dallas, Texas
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Fort Wayne, Indiana
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Fremont, Nebraska
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Huntsville, Alabama
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Iowa City, Iowa
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Kalispell, Montana
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Oklahoma City, Oklahoma
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Orlando, Florida
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Pottstown, Pennsylvania
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Salt Lake City, Utah
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Santa Fe, New Mexico
Study site
Sarasota, Florida
Study site
Sellersville, Pennsylvania
Study site
Stockton, California

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Ukraine14 sites

Study site
Cherkassy
Study site
Chernihiv
Study site
Chernivtsy
Study site
Dnipro
Study site
Donetsk
Study site
Ivano-Frankivsk
Study site
Kiev
Study site
Lutsk
Study site
Lviv
Study site
Odesa
Study site
Poltava
Study site
Ternopil
Study site
Vinnitsa
Study site
Zaporizhzhya

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Canada8 sites

Study site
Alberta, British Columbia
Study site
Calgary, Alberta
Study site
Edmonton, Alberta
Study site
Montreal, Quebec
Study site
Oshawa, Ontario
Study site
Sherbrooke, Quebec
Study site
Thunder Bay, Ontario
Study site
Winnipeg, Manitoba

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Slovakia5 sites

Study site
Bardejov
Study site
Bratislava
Study site
Košice
Study site
Lučenec
Study site
Prešov

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Bosnia and Herzegovina4 sites

Study site
Banja Luka
Study site
Mostar
Study site
Sarajevo
Study site
Tuzla

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Chile4 sites

Study site
Antofagasta
Study site
Osorno
Study site
Santiago
Study site
Temuco

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Latvia3 sites

Study site
Daugavpils
Study site
Riga
Study site
Ventspils

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Mexico3 sites

Study site
Córdoba
Study site
Guadalajara Jalisco
Study site
Mexico City

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Belgium2 sites

Study site
Brussels
Study site
Genk

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Belarus1 site

Study site
Minsk

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Moldova1 site

Study site
Chisinau

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About this study

Official title: A Phase 2, Randomized, Parallel Group, Multi Center, Multi National Study for the Evaluation of Safety of Four Fixed Dose Regimens of DU-176b in Subjects With Non- Valvular Atrial Fibrillation

Conditions: Atrial Fibrillation, Thromboembolism
Being tested: Edoxaban (DU-176b), warfarin
Keywords: Anti-coagulant, Non-valvular, Venous Thromboembolism, Prevention of Blood Clots, Atrial Fibrillation, Non-valvular atrial fibrillation
Medical subject headings: Atrial Fibrillation, Thromboembolism, Venous Thromboembolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Edoxaban (DU-176b)Drug
30mg tablet once daily
Edoxaban (DU-176b)Drug
60mg tablet once daily
Edoxaban (DU-176b)Drug
30mg tablet two times a day
Edoxaban (DU-176b)Drug
60mg tablet two times a day
warfarinDrug
warfarin tablets

Study groups in NCT00504556
Study group	Role	What they receive
1	Experimental	DU-176b 30mg tablet once daily Receives: Drug: Edoxaban (DU-176b)
2	Experimental	DU-176b 60mg once daily Receives: Drug: Edoxaban (DU-176b)
3	Experimental	DU-176b 30mg b.i.d. Receives: Drug: Edoxaban (DU-176b)
4	Experimental	DU-176b 60mg tablets two times a day Receives: Drug: Edoxaban (DU-176b)
5	Active comparator	warfarin tablets Receives: Drug: warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

Adjudicated Incidence of Bleeding Events
Adjudicated Incidence of Bleeding Events during treatment period
Measured: 3 months
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities
Measured: 3 months

Secondary outcomes (10)

Incidence of Major Adverse Cardiac Events MACE)
MACE is defined as the composite of stroke [ischemic or hemorrhagic], Systemic embolic event (SEE), Myocardial Infarction (MI), Cardiovascular (CV) death, and hospitalization for any cardiac condition
Measured: 3 months
Effects on Biomarker D-dimer
Mean (SD) change from baseline in D-dimer
Measured: 3 months
Effects on Biomarker Prothrombin Fragments
Mean (SD) change from baseline in Prothrombin Fragments 1 and 2 (F1 and F2)
Measured: 3 months
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Median (min, max) values of Cmin,ss; Cmax,ss
Measured: 3 months
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
Median (min, max) values of AUCss
Measured: 3 months
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker anti-Factor Xa [FXa] activity on Day 28, 1-3 hours post dose.
Measured: Day 28
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker endogenous FX activity on Day 28, 1-3 hours post dose.
Measured: Day 28
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker prothrombinase induced clotting time [PICT] on Day 28, 1-3 hours post dose.
PICT was determined by PICT aasay which is a plasma based functional assay to determine the anticoagulant activity on FXa and FIIa inhibition.
Measured: Day 28
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker prothrombin time (PT) on Day 28, 1-3 hours post dose.
Measured: Day 28
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
Mean (SD) change from baseline in biomarker International Normalized Ratio (INR) on Day 28, 1-3 hours post dose.
Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Jun 2008

First posted20 Jul 2007 (estimated)
Study startJun 2007
Primary completionJun 2008
Study completionJun 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Atrial FibrillationStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 1,146 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00504556
Sponsor's protocol ID: DU176b-PRT018
Status last verified: Mar 2015
First submitted: 18 Jul 2007
Last updated: 26 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

All Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Randomized, Parallel Group, Multi Center, Multi National Study for the Evaluation of Safety of Four Fixed Dose Regimens of DU-176b in Subjects With Non- Valvular Atrial Fibrillation
ClinicalTrials.gov ID: NCT00504556
Acronym / sponsor ID: DU176b-PRT018
Conditions: Atrial Fibrillation, Thromboembolism
Keywords: Anti-coagulant, Non-valvular, Venous Thromboembolism, Prevention of Blood Clots, Atrial Fibrillation, Non-valvular atrial fibrillation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,146 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Study start: Jun 2007
Primary completion: Jun 2008 (actual)
Study completion: Jun 2008 (actual)
First posted: 20 Jul 2007 (estimated)
Results: Posted 13 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
1	Experimental	Drug: Edoxaban (DU-176b)DU-176b 30mg tablet once daily
2	Experimental	Drug: Edoxaban (DU-176b)DU-176b 60mg once daily
3	Experimental	Drug: Edoxaban (DU-176b)DU-176b 30mg b.i.d.
4	Experimental	Drug: Edoxaban (DU-176b)DU-176b 60mg tablets two times a day
5	Active comparator	Drug: warfarinwarfarin tablets

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Male or female, 18 to 80 years old.
Able to provide written informed consent.
Persistent non-valvular AF supported by abnormal electrocardiogram (ECG)
A congestive heart failure, hypertension, age ≥ 75 years, diabetes, and prior stroke (CHADS2) index score of at least 2

Key exclusion criteria (3 listed)

Subjects with mitral valve disease or previous valvular heart surgery
Known contraindication to any anticoagulant including vitamin K antagonists such as warfarin
Known or suspected hereditary or acquired bleeding or coagulation disorder

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Edoxaban (DU-176b)30mg tablet once daily	Drug	1
Edoxaban (DU-176b)60mg tablet once daily	Drug	2
Edoxaban (DU-176b)30mg tablet two times a day	Drug	3
Edoxaban (DU-176b)60mg tablet two times a day	Drug	4
warfarinwarfarin tablets	Drug	5

Primary outcome

Adjudicated Incidence of Bleeding Events
Time frame: 3 months
Adjudicated Incidence of Bleeding Events during treatment period
Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)
Time frame: 3 months
liver enzyme (ALT and/or AST) and/or bilirubin (TBL) abnormalities

10 secondary outcomes

Incidence of Major Adverse Cardiac Events MACE)
Time frame: 3 months
Effects on Biomarker D-dimer
Time frame: 3 months
Effects on Biomarker Prothrombin Fragments
Time frame: 3 months
Pharmacokinetics (Cmin, Cmax) of DU-176b in Subjects Receiving DU-176b
Time frame: 3 months
Pharmacokinetics (AUC) of DU-176b in Subjects Receiving DU-176b
Time frame: 3 months
Effects on Pharmacodynamic Biomarker Anti-Factor Xa Activity in Subjects Receiving DU-176b
Time frame: Day 28
Effects on Pharmacodynamic Biomarker (Endogenous FX Activity) in Subjects Receiving DU-176b
Time frame: Day 28
Effects on Pharmacodynamic Biomarker PICT Activity in Subjects Receiving DU-176b
Time frame: Day 28
Effects on Pharmacodynamic Biomarker PT in Subjects Receiving DU-176b
Time frame: Day 28
Effects on Pharmacodynamic Biomarker INR in Subjects Receiving DU-176b
Time frame: Day 28

Results and safety

Results posted to the registry on 13 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DU-176b 30mg qd	235	200
DU-176b 30mg Bid	245	207
DU-176b 60mg qd	235	204
DU-176b 60mg Bid	180	52
Warfarin Tablets	251	226

Primary outcome: Adjudicated Incidence of Bleeding Events

Time frame: 3 months. Number (95% Confidence Interval). Unit: percent of subjects with outcome event

Measure	DU-176b 30mg qd n = 235	DU-176b 30mg Bid n = 244	DU-176b 60mg qd n = 234	DU-176b 60mg Bid n = 180	Warfarin Tablets n = 250
All bleeding	5.5 (3.0 to 9.3)	12.7 (8.8 to 17.5)	7.3 (4.3 to 11.4)	18.3 (13.0 to 24.8)	8.0 (5.0 to 12.1)
Major or clinically relevant non-major bleed	3.0 (1.2 to 6.0)	7.8 (4.8 to 11.9)	3.8 (1.8 to 7.2)	10.6 (6.5 to 16.0)	3.2 (1.4 to 6.2)
Major bleed	0 (0 to 1.6)	2.0 (0.7 to 4.7)	0.4 (0 to 2.4)	3.3 (1.2 to 7.1)	0.4 (0 to 2.2)

DU-176b 30mg qd vs Warfarin Tablets: p = .367, Fisher Exact
DU-176b 30mg Bid vs Warfarin Tablets: p = .104, Fisher Exact
DU-176b 60mg qd vs Warfarin Tablets: p = .864, Fisher Exact

Population analysed: safety analysis set

Primary outcome: Percent of Subjects With Liver-related Laboratory Marked Abnormalities (MA)

Time frame: 3 months. Number (95% Confidence Interval). Unit: percent subjects with liver related MA

Measure	DU-176b 30mg qd n = 235	DU-176b 30mg Bid n = 244	DU-176b 60mg qd n = 234	DU-176b 60mg Bid n = 180	Warfarin Tablets n = 250
ALT, total >= 3x ULN	1.3 (0.3 to 3.8)	0.9 (.01 to 3.0)	2.6 (1.0 to 5.6)	1.7 (0.4 to 5.0)	1.2 (0.3 to 3.5)
AST, total >= 3x ULN	0.9 (0.1 to 3.1)	0.9 (0.1 to 3.0)	1.3 (0.3 to 3.8)	1.2 (0.1 to 4.1)	0.8 (0.1 to 2.9)
total bilirubin, total >= 2x ULN	0.9 (0.1 to 3.1)	1.3 (0.3 to 3.7)	0.4 (0 to 2.4)	2.9 (1.0 to 6.7)	1.6 (0.4 to 4.1)
ALT or AST >=3 x ULN	1.3 (0.3 to 3.8)	0.9 (0.1 to 3.0)	3.1 (1.2 to 6.2)	1.7 (0.4 to 5.0)	1.6 (0.4 to 4.1)
ALT or AST >=3 x ULN and TBL >=2 x ULN	0 (0 to 1.6)	0.4 (0 to 2.3)	0 (0 to 1.6)	0.6 (0 to 3.2)	0 (0 to 1.5)

Population analysed: safety analysis set

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DU-176b 30mg qd	10 of 235 (4.3%)	3 of 235 (1.3%)	Not reported
DU-176b 30mg Bid	16 of 244 (6.6%)	8 of 244 (3.3%)	Not reported
DU-176b 60mg qd	15 of 234 (6.4%)	4 of 234 (1.7%)	Not reported
DU-176b 60mg Bid	14 of 180 (7.8%)	10 of 180 (5.6%)	Not reported
Warfarin Tablets	11 of 250 (4.4%)	22 of 250 (8.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Related trials for Atrial Fibrillation

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

91 sites in 12 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Edoxaban (DU-176b) and warfarin in people with Atrial Fibrillation and Thromboembolism, run by Daiichi Sankyo at 91 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in Russia, United States, Ukraine, Canada, Slovakia and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjudicated Incidence of Bleeding Events (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00504556.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2019.