ANZCTR - Registration

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:00pm (AEST) on Thursday 10th of April for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The ANZCTR website is back online for trial registration and updates. We apologise for any inconvenience caused while the site was inactive.

With activity expected to increase on the ANZCTR again, there may be extended wait times while we process pending studies, with priority being given to those trials submitted in February. Thank you for your patience.

Reset your password and enable multi-factor authentication (MFA)

For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.

Go to the Login page, click ‘reset password’ and follow the instructions.
Check your email for the link to set a new password.
Create a new password that meets requirements.
Return to the Login page and enter your new password. A verification code will be sent to your email.
Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

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

ACTRN12613000703707

Ethics application status

Approved

Date submitted

24/06/2013

Date registered

27/06/2013

Date last updated

27/06/2013

Type of registration

Prospectively registered

Titles & IDs

Public title

An observational study comparing efficacy and safety of warfarin brands in cardiovascular patients

Scientific title

An open-label, prospective, observational study comparing efficacy and safety of two warfarin brands in adult patients already receiving warfarin treatment

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Atrial fibrillation

Venous thrombosis

Pulmonary embolism

Recurrent emboli

Prosthetic valve replacement

Acute myocardial infarction (to prevent systemic embolism)

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

The participants will be opportunistically followed up for the clinical outcome of warfarin for 6 months. The participants will continue with their usual treatment with the same brand of warfarin for the whole study period. Warfarin dosage adjustment is determined by physicians as necessary at any time during the study period in accordance with the standard treatment guidelines.

Intervention code [1]

Not applicable

Comparator / control treatment

This study is designed as an open label, prospective, observational study. Three hundred patients currently receiving warfarin (any brand) treatment will be recruited and allocated into 2 groups. Group I is the patients receiving the brand Coumadin (n=150) and Group II is the patients receiving the brand Marevan (n=150). The participants will be followed opportunistically as their usual anticoagulant visits. The duration of study is approximately 1 year (from 1 July 2013– 31 July 2014).

Control group

Active

Outcomes

Primary outcome [1]

Percentage of the patients whose International Normalized Ratio fall within and outside target ranges

Timepoint [1]

For 6 months after enrolment

Secondary outcome [1]

Safety profile (adverse drug events). The significant adverse events of warfarin are bleeding at any tissues. The adverse events will be evaluated by a questionnaire given to the patients on each visit about "head to toe" disorders that they experience during each brand treatment period. Also the investigator will interview the patients and evaluate the adverse events to double check with the answers in the questionnaire. The data from the questionnaire and interview will be compared with warfarin concentrations and INR values to confirm the drug-induced adverse events possibility.

Timepoint [1]

For 6 months after enrolment

Eligibility

Key inclusion criteria

1. Age greater than or equal to 18 years
2. Receiving warfarin treatment

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Age less than 18 years
2. Pregnancy or breast feeding
3. Non-adherence tendency
4. Psychiatric disorder or dementia
5. Taking any medications, food or dietary supplement that significantly interact with warfarin
6. Limited English communication proficiency

Study design

Purpose

Duration

Selection

Timing

Statistical methods / analysis

Statistical Package for Social Sciences (SPSS version 15.0) will be used for data analysis. Student’s paired t-test will be used for comparison of continuous variables, including mean warfarin dose requirement, warfarin concentrations in plasma and percentage of adverse events. Two-way ANOVA will be used to detect the differences of ratios of means INR and warfarin concentration between the groups. A Chi-square test will be used for the analysis and comparison of the proportions of participants with INR “within target range” and “outside target range” between the two brands. Time-in-therapeutic-range (TTR) of these two groups will also be compared by using a Student’s t-test for independent samples.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/07/2013

Actual

Date of last participant enrolment

Anticipated

31/01/2014

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

300

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Queen Elizabeth Hospital - Woodville

Recruitment postcode(s) [1]

5011 - Woodville South

Funding & Sponsors

Funding source category [1]

University

Name [1]

Therapeutcs Research Centre University of South Australia

Address [1]

37a Woodville Road Woodville South SA 5011

Country [1]

Australia

Primary sponsor type

University

Name

Therapeutcs Research Centre, University of South Australia

Address

37a Woodville Road
Woodville South
SA 5011

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee (TQEH/LMH/MH)

Ethics committee address [1]

Basil Hetzel Institute DX465101
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

10/05/2013

Ethics approval number [1]

HREC/13/TQEHLMH/45

Ethics committee name [2]

UniSA's Human Research Ethics Committee

Ethics committee address [2]

Research and Innovation Services
Ethics and Integrity
Mawson Lakes Campus 
University of South Australia 
GPO Box 2471, Adelaide, SA, 5001

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

21/06/2013

Ethics approval number [2]

Summary

Brief summary

Substitution of an innovator to a generic drug product has been continuously rising. In the US, approximately $8 billion to $10 billion is the average cost saving per year of brand substitution and the generic drug prescription has increased from 19% in 1984 to 60-70% in 2009. The increase in drug brand substitution is a call for scientific
attention of the appropriateness of available bioequivalence (BE) study guidelines at present. If two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same. The conclusion of BE studies is based on the assumption that if the test and reference drug products exhibit similar in vitro (i.e. acceptable drug content, similar dissolution/release profile) and in vivo performance (i.e. acceptable bioavailability), these drug products should possess therapeutic equivalence which includes efficacy and safety. However, because bioequivalence studies are conducted in healthy volunteers, these studies may or may not provide definitive evidence to guarantee the therapeutic equivalence in patients.
This study aims to compare efficacy and safety of two warfarin products marketed in Australia, namely Coumadin  registered trademark or Marevan registered trademark. The study is designed as an openlabel,
prospective, observational trial. A total of 300 patients who
are prescribed with either brand of warfarin will be recruited in accordance with the inclusion and exclusion criteria.
The patients will be followed up opportunistically as their medical appointments for anticoagulant evaluation. The
additional 5 mL of the participant blood samples and about 25 mL of urine samples will be collected at each visit.
Total and free racemic, R- and S-warfarin enantiomer concentration in plasma, as well as 4',6,7,8, and 10hydroxywarfarin metabolites in urine will be quantified by LC MS/MS. The efficacy of the two warfarin brands will be
compared by evaluating International Normalized Ratio (INR) values. The safety profile evaluation will be achieved by recording any adverse drug reactions or adverse events in a questionnaire. The frequency of adverse events
reported from two groups of patients will be analyzed and compared.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Ms Rachada To-a-nan

Address

Therapeutics Research Centre Basil Hetzel Institute for Translational Research 37a Woodville Road, Woodville South SA 5011

Country

Australia

Phone

+61 8 8222 7719

Fax

[email protected]

Contact person for public queries

Name

Tom Robertson

Address

Therapeutics Research Centre Basil Hetzel Institute for Translational Research 37a Woodville Road, Woodville South SA 5011

Country

Australia

Phone

+61 8 8222 6521

Fax

[email protected]

Contact person for scientific queries

Name

Michael Roberts

Address

Sansom Institute, University of South Australia G.P.O. Box 2471, Adelaide SA 5001

Country

Australia

Phone

+61 8 8302 2816

Fax

[email protected], [email protected]

No information has been provided regarding IPD availability

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

Documents added manually

Documents added automatically