Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000054415
Ethics application status
Approved
Date submitted
16/10/2006
Date registered
16/01/2007
Date last updated
13/11/2019
Date data sharing statement initially provided
13/11/2019
Date results information initially provided
13/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Interactions between herbal medicines and the anticoagulant warfarin
Scientific title
Pharmacokinetic and pharmacodynamic interactions between herbal medicines (cranberry, garlic, echinacea, policosonal, fish oil, CoEnzyme Q10, Soy, feverfew, milk thistle and evening primrose oil) and the anticoagulant warfarin - Randomised clinical trials in healthy male subjects
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug interactions of warfarin with herbal medicines in healthy male subjects. Relevant to Stroke prevention and people receiving warfarin 1547 0
Condition category
Condition code
Stroke 1646 1646 0 0
Other 1647 1647 0 0

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In each 3-treatment cross over clinical trial 2 herbal medicine will be studied. Dosage of the herbal medicines mentioned here are based upon the current information and subject to change in accordence with the latest clinical evidence which will be decided prior to each clinical trial. Variations in pharmacokinetics and pharmacodynamics of warfarin will be compared when single dose of 25 mg warfarin given alone orally (control) and when single dose of 25 mg warfarin given after 2 weeks of pre-treatment with each herbal medicine administered orally (intervention). Herbal medicines intake will be continued for one more week after warfarin administration. In total 10 herbs will be studied in 5 clinical trials. List of the proposed herbs are cranberry (6 X 500mg capsules per day of General Nutrition Corporation (GNC) cranberry juice concentrate capsules), garlic (equivalent to 4 g of fresh garlic), echinacea (4 X 1.27g tablets daily of Medi herb echinacea premium tablets), policosonal (20 mg daily), fish oil (4 g per day), CoEnzyme Q10 (50 mg per day), Soy (3.5 mg per day of phospholipids) , feverfew (100 mg of powdered feverfew daily), Milk thistle (250 mg daily of silymarin) and evening primrose oil (300 mg daily of fixed oil) .
Intervention code [1] 1403 0
Treatment: Drugs
Comparator / control treatment
Single dose of 25 mg warfarin given alone orally (control)
Control group
Active

Outcomes
Primary outcome [1] 2272 0
Studying alterations in pharmacokinetics and pharmacodynamics of S-warfarin. When warfarin is given alone and when given alone with herbal medicines. Pharmadynamic variations will be assessed by measuring International Normalised Ratio (INR) from the all the blood samples collected before and after warfarin administration at 8:00 A.M on the days of collection. Pharmacokinetic variations will be accessed my measuring S-warfarin concentration in plasma from samples stored at -70 C for all sample points.
Timepoint [1] 2272 0
Blood samples are collected at -24, -48, 0 hr before warfarin administration and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hr after warfarin adminstration in all the three treatment periods in each trial.
Secondary outcome [1] 3977 0
Pharmacokinetics of R-warfarin
Timepoint [1] 3977 0
Measured from the stored blood samples at -70 C for 0 to 168 h sample points after warfarin dosing in all phases.
Secondary outcome [2] 3978 0
Platelet aggregation is measure with -24 hr blood sampels collected before warfarin administration in all the three treatment periods.
Timepoint [2] 3978 0

Eligibility
Key inclusion criteria
Healthy subjects not taking other medicines including any supplements, who are non-smokers.
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Any condition with could effect pharmacokinetic and pharmacodynamics of warfarin.

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)
Central allocation by study administrator
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a computer based random number generator
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
A series of 5 sub-studies investigating the effect of 2 herbs (given seperately) in each substudy using a 3-treatment cross-over design with 2 weeks pre-treatment and 2 week washout
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2005
Actual
24/01/2005
Date of last participant enrolment
Anticipated
Actual
26/10/2009
Date of last data collection
Anticipated
Actual
2/11/2009
Sample size
Target
60
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1792 0
Government body
Name [1] 1792 0
National Health and Medical Research Council
Country [1] 1792 0
Australia
Primary sponsor type
Individual
Name
Prof Andrew McLachlan
Address
Country
Secondary sponsor category [1] 1612 0
Individual
Name [1] 1612 0
A/Prof Ken Williams
Address [1] 1612 0
Country [1] 1612 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3347 0
Human Research Ethics Commitees of the Univeristy of Sydney
Ethics committee address [1] 3347 0
Ethics committee country [1] 3347 0
Australia
Date submitted for ethics approval [1] 3347 0
Approval date [1] 3347 0
09/12/2004
Ethics approval number [1] 3347 0
7839
Ethics committee name [2] 3348 0
St Vincent's Hospital
Ethics committee address [2] 3348 0
Ethics committee country [2] 3348 0
Australia
Date submitted for ethics approval [2] 3348 0
Approval date [2] 3348 0
09/12/2004
Ethics approval number [2] 3348 0
7839
Ethics committee name [3] 3349 0
Darlinghurst
Ethics committee address [3] 3349 0
Ethics committee country [3] 3349 0
Australia
Date submitted for ethics approval [3] 3349 0
Approval date [3] 3349 0
27/09/2004
Ethics approval number [3] 3349 0
H04/073

Summary
Brief summary
This study will explore the clinical significane of interactions between commonly used herbal medicines with the anti-coagulant warfarin. In total 5 independent three- treatment cross over randomnised clinical trials will be conducted with similar study design. In each trial 2 herbs will be studied.
Trial website
Trial related presentations / publications
https://www.ncbi.nlm.nih.gov/pubmed/20573086
https://www.ncbi.nlm.nih.gov/pubmed/18516070
https://www.ncbi.nlm.nih.gov/pubmed/15801937
https://www.ncbi.nlm.nih.gov/pubmed/15089812
Public notes

Contacts
Principal investigator
Name 27337 0
Address 27337 0
Country 27337 0
Phone 27337 0
Fax 27337 0
Email 27337 0
Contact person for public queries
Name 10592 0
Professor Andrew McLachlan
Address 10592 0
Faculty of Pharmacy
University of Sydney
NSW 2006
Country 10592 0
Australia
Phone 10592 0
+61 2 93514452
Fax 10592 0
+61 2 93514391
Email 10592 0
[email protected]
Contact person for scientific queries
Name 1520 0
Professor Andrew McLachlan
Address 1520 0
Faculty of Pharmacy
University of Sydney
NSW 2006
Country 1520 0
Australia
Phone 1520 0
+61 2 93514452
Fax 1520 0
+61 2 93514391
Email 1520 0
[email protected]

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.