ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12607000222448

Ethics application status

Approved

Date submitted

19/04/2007

Date registered

24/04/2007

Date last updated

6/02/2020

Date data sharing statement initially provided

6/02/2020

Date results provided

6/02/2020

Type of registration

Retrospectively registered

Titles & IDs

Public title

The effect of oral rivaroxaban in treating and in the long term prevention in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism.

Scientific title

The effect of oral direct factor Xa inhibitor rivaroxaban in treating (Bay 59-7939 / 11702) and in the long term prevention (Bay 59-7939 / 11899) in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism.

Secondary ID [1]

ClinicalTrials.org: NCT00439725

Secondary ID [2]

ClinicalTrials.org: NCT00439777

Universal Trial Number (UTN)

Trial acronym

Einstein VTE III and Einstein Extension

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Deep vein thrombosis

Pulmonary embolism

Condition category

Condition code

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients allocated to the rivaroxaban arm of the prevention trial (Bay 59-7939 / 11702) will receive rivaroxaban 15 mg twice daily orally for a total of 3 weeks and thereafter patients will receive rivaroxaban 20 mg once daily.

Patients from both the rivaroxaban and enoxaparin treatment arms will be treated for 3, 6 or 12 months depending on the risk profile of the patients and the preference of the investigator.

Patients continuing in the extension study (Bay 59-7939 / 11899) will receive rivaroxaban or matching placebo 20 mg orally once daily. Treatment duration will be 6 or 12 months and should be indicated prior to randomisation.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Patients allocated to the comparator arm will receive enoxaparin 1.0 mg / kg twice daily for at least 5 days in combination with vitamin K antagonist given subcutaneously. Enoxaparin will continue until the International Normalised Ratio is greater than or equal to 2.0 on two consecutive occasions, with an advised overlap with VKA for 4 to 5 days.

Control group

Active

Outcomes

Primary outcome [1]

The primary efficacy outcome is symptomatic recurrent venous thromboembolism (VTE).

Timepoint [1]

Measured at the first occurrence from time of randomisation, then once a month until the end of the follow up period.

Secondary outcome [1]

Clinically relevant bleeding.

Timepoint [1]

Measured at the first occurrence from time of randomisation, then once a month until the end of the follow up period.

Eligibility

Key inclusion criteria

Inclusion criteria for Bay 59-7939 / 11702. Confirmed acute symptomatic proximal deep vein thrombosis or confirmed acute symptomatic pulmonary embolism.
Active bleeding.Inclusion criteria for Bay 59-7939 / 11899.Confirmed acute symptomatic deep vein thrombosis or pulmonary embolism who have been treated for 6 or 12 months with vitamin K antagonist.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion criteria for 11702Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of deep vein thrombosis (DVT) and/or pulmonary embolism (PE).Other indication for VKA other than DVT and/or PE. More than 36 hours pre-randomisation treatment with therapeutic dosages of low molecular weight heparin / fondaparinux or more than a single dose of VKA prior to randomisation.Significant renal or liver disease.
Exclusion criteria for 11899Other indication for VKA other than DVT and/or PE.Significant renal or liver disease.Systolic blood pressure greater than 180 mmHg or diastolic greater than 110 mmHgActive bleeding. Bacterial endocarditis.Active bleeding or high risk for bleeding.Life expectancy less than 3 months.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

An interactive voice response system (IVRS) will be used to allocate treatments.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computer generated random code.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

The extension trial (Bay 59-7939 / 11899) is a double blind (patients, assessors, clinician and data analyst), placebo controlled trial for patients with confirmed symptomatic deep vein thrombosis or pulmonary embolism who completed 6 or 12 months of treatment with rivaroxaban.

Phase

Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

24/04/2007

Actual

22/03/2007

Date of last participant enrolment

Anticipated

Actual

12/03/2011

Date of last data collection

Anticipated

Actual

1/12/2011

Sample size

Target

5193

Accrual to date

Final

8257

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,SA,WA,VIC

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Bayer Australia Limited

Address [1]

875 Pacific Highway Pymble NSW 2073

Country [1]

Australia

Funding source category [2]

Commercial sector/Industry

Name [2]

Johnson and Johnson Pharmaceutical Research Development

Address [2]

Raritan NJ 08869

Country [2]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Bayer Australia Limited

Address

875 Pacific Highway Pymble NSW 2073

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Collaborator 11702b)
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Collaborator 11899)

Address [1]

Raritan, New Jersey

Country [1]

United States of America

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Queen Elizabeth Hospital

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

19/03/2007

Ethics approval number [1]

2007018

Ethics committee name [2]

The Gold Coast Hospital

Ethics committee address [2]

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

28/03/2007

Ethics approval number [2]

200715

Summary

Brief summary

This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic PE with or without symptomatic DVT (Einstein-PE). (11702b)

This is a multicenter, randomized, double-blind, placebo-controlled, event-driven, superiority study for efficacy. Patients with confirmed symptomatic DVT or PE who completed 6 or 12 months of treatment with rivaroxaban or VKA are eligible for this trial (Einstein-Extension study). (11899)

Trial website

Trial related presentations / publications

Cohen AT, Dobromirski M. The use of rivaroxaban for short- and long-term treatment of venous thromboembolism. Thromb Haemost. 2012 Jun;107(6):1035-43. doi: 10.1160/TH11-12-0859. Epub 2012 Feb 28. Review. 

EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. Epub 2010 Dec 3. 


EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26. 

Prins MH, Lensing AW. Derivation of the non-inferiority margin for the evaluation of direct oral anticoagulants in the treatment of venous thromboembolism. Thromb J. 2013 Jul 6;11(1):13. doi: 10.1186/1477-9560-11-13. 

Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Raskob GE, Berkowitz SD, Wells PS; EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013 Sep 20;11(1):21. doi: 10.1186/1477-9560-11-21. 

Wang Y, Wang C, Chen Z, Zhang J, Liu Z, Jin B, Ying K, Liu C, Shao Y, Jing Z, Meng IL, Prins MH, Pap AF, Müller K, Lensing AW; Chinese EINSTEIN Investigators. Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies. Thromb J. 2013 Dec 16;11(1):25. doi: 10.1186/1477-9560-11-25. 

van Bellen B, Bamber L, Correa de Carvalho F, Prins M, Wang M, Lensing AW. Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism. Curr Med Res Opin. 2014 May;30(5):829-37. doi: 10.1185/03007995.2013.879439. Epub 2014 Jan 22.

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Professor Tim Brighton

Address

Department of Haematology
Prince of Wales Hospital
Barker Street
Randwick NSW 2031

Country

Australia

Phone

+61 2 93829013

Fax

+61 2 93829116

tim.brighton@sesaihs.health.nsw.gov.au

Contact person for scientific queries

Name

Professor Tim Brighton

Address

Department of Haematology
Prince of Wales Hospital
Barker Street
Randwick NSW 2031

Country

Australia

Phone

+61 2 93829013

Fax

+61 2 93829116

tim.brighton@sesaihs.health.nsw.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically