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Trial registered on ANZCTR


Registration number
ACTRN12616001544460
Ethics application status
Approved
Date submitted
13/10/2016
Date registered
9/11/2016
Date last updated
9/11/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of Sublingual (under the tongue) Rosuvastatin/Crestor (cholesterol/statin medication) in reducing the side effects experienced in subjects with high cholesterol & a history of cardiovascular disease (heart attack, coronary artery disease) with a known statin intolerance.
Scientific title
Clinical effects of Sublingually Administered Rosuvastatin in subjects who are Statin Intolerant - SARSI -001
Secondary ID [1] 290330 0
Nil Known
Universal Trial Number (UTN)
U1111-1188-6660
Trial acronym
SARSI - oo1 - Sublingually Administered Rosuvastatin in subjects who are Statin Intolerant
Linked study record

Health condition
Health condition(s) or problem(s) studied:
coronary artery disease 300599 0
Hyperlipidaemia 300847 0
Diabetes 300848 0
peripheral vascular disease 300849 0
Condition category
Condition code
Cardiovascular 300450 300450 0 0
Coronary heart disease
Cardiovascular 300451 300451 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial involves the sublingual administration of 5mg Rosuvastatin and placebo on a daily nocturnal basis in the subjects home. The trial drug is administered for 6 weeks with 2 week washout and another 6 weeks of matching placebo (or visa versa depending on randomisation schedule. Demonstration using sublingual placebo administration will occur at randomisation visit and subject compliance will be assessed at each visit by way of counting the number of tablets returned : number of days since randomisation. Fasting blood tests will also be taken prior to each visit to monitor safety + progress of cholesterol levels
Intervention code [1] 296142 0
Treatment: Drugs
Comparator / control treatment
The study is a cross over study - the subject will act as their own control
Subjects will be asked to take sublingual "5mg" placebo or sublingual 5mg crestor on a nightly basis at home for 6 weeks either in arm 1 or arm 2 and the repeat the process for another 6 weeks. Neither subject or investigator know which arm the patient is on active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 299885 0
Change in Myalgia/muscle aches symptoms
Timepoint [1] 299885 0
Myalgia will be evaluated by subjects reporting adverse events at day 7 post drug administration. A myalgia score using analogue tool will occur at day 21 & 42 in 1st arm post administration and day 84 & 105 post administration in 2nd arm.
Elevated muscle enzymes (CK) will be measured at days 7, 21 &42 post drug administration in 1st arm and day 84 & 105 post drug administration in 2nd arm.
As we are blinded, 1st arm may be rosuvastatin or placebo + 2nd arm may be rosuvastatin or placebo.
Primary outcome [2] 300096 0
change in total blood cholesterol
Timepoint [2] 300096 0
assessed by fasting blood test at 7, 21 and, 42 days post sublingual drug administration in 1st arm and days 84 & 105 post sublingual drug administration in 2nd arm.
As we are blinded, 1st arm may be rosuvastatin or placebo + 2nd arm may be rosuvastatin or placebo.
Secondary outcome [1] 328397 0
stable memory
Timepoint [1] 328397 0
assessed using Montreal cognitive assessment tool at day 42 post sublingual drug administration in 1st arm and day 105 post sublingual drug administration in 2nd arm
As we are blinded, 1st arm may be rosuvastatin or placebo + 2nd arm may be rosuvastatin or placebo.

Eligibility
Key inclusion criteria
Has suffered side effects attributable to the statin including myalgia, abnormal liver function tests, and/or memory problems.
Has stopped taking statins more than 1 month prior to enrolment
Has existing total cholesterol of > 5.5 mmol/L
Has a history of cardiovascular ischaemic heart disease and is not yet at target levels TC< 4.0mmol/L

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has uncontrolled diabetes, defined by a HbA1c > 9% as measured at visit 1
2. Has alanine aminotransferase (ALT) > 1.5 times ULN as measured at visit 1
3. Has aspartate aminotransferase (AST) > 1.5 times ULN as measured at visit 1
4. Has creatine kinase (CK) > 1.5 times ULN as measured at visit 1
5. Has triglycerides (TG) > 4.5 mmol/L as measured at visit 1
6. Has evidence of renal impairment with a serum creatinine of > 200 µmol/L as measured at visit 1
7. Has known drug or alcohol dependency within 6 months of visit 1
8. A woman receiving hormonal therapy, including hormone replacement, any oestrogen agonist/antagonist, or oral contraceptives
9. A woman of childbearing potential not using a an acceptable method of birth control (e.g. hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide)
10. Woman who is pregnant or breast feeding
11. Any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation was concealed as to when subject would be on the active or placebo drug - either the 1st arm or 2nd arm.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A letter A or B was drawn from a container to allocate which container they would start on and it would change to the other letter for the 2nd 6 weeks. A is either active drug or placebo or B is active drug or placebo.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
In order to detect an effect size of 1.4mmol / L between treated and non-treated subjects for total cholesterol with a standard deviation of 1.41 at an alpha level of 0.025 and beta =0.95, we need 16 subjects. Assuming a dropout/noncompliance rate of 20% we inflate the sample size to 20. We used Stata v.14 to compute the required sample size for a simple crossover trial that is AB/BA. This method is similar to a one-sample t-test for the difference between treatment regimes, except that this calculation uses the non-central t-distribution. Data will be analysed as two-sample t-test comparing changes within and between rosuvastatin treatment and no treatment allocations after ensuring there was no carry over, sequence or period effect. Paired two-sample t-test will be used for within
allocation comparisons whereas unpaired two-sample t-test will be used for between treatment allocation comparisons. Continuous variables will be expressed as mean ± SD, categorical variables as frequency and percentage. A p-value of = 0.05 will be considered statistically significant. All analyses will be performed in Stata 14.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
4/11/2016
Date of last participant enrolment
Anticipated
1/12/2016
Actual
Date of last data collection
Anticipated
1/03/2017
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 14490 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 294712 0
Government body
Name [1] 294712 0
AusIndustry
Country [1] 294712 0
Australia
Primary sponsor type
Individual
Name
Dr Gregory Szto
Address
Peninsula Heart Centre
Suite 11, Peninsula Private Hospital 525 McClelland drive Frankston 3199 Vic
Country
Australia
Secondary sponsor category [1] 293729 0
None
Name [1] 293729 0
Address [1] 293729 0
Country [1] 293729 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296134 0
Monash Health
Ethics committee address [1] 296134 0
Ethics committee country [1] 296134 0
Australia
Date submitted for ethics approval [1] 296134 0
27/09/2016
Approval date [1] 296134 0
19/10/2016
Ethics approval number [1] 296134 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69578 0
Dr Gregory Szto
Address 69578 0
Peninsula Heart Centre, 525 McClelland Drive
Frankston Vic 3199
Country 69578 0
Australia
Phone 69578 0
+61 397890088
Fax 69578 0
+61 397898866
Email 69578 0
greg@peninsulaheart.com.au
Contact person for public queries
Name 69579 0
Vikki OShea
Address 69579 0
Peninsula Heart Centre, 525 McClelland Drive
Frankston Vic 3199
Country 69579 0
Australia
Phone 69579 0
+61 397890088
Fax 69579 0
+61 397898866
Email 69579 0
vikki@peninsulaheart.com.au
Contact person for scientific queries
Name 69580 0
David Kannar
Address 69580 0
Peninsula Heart Centre, 525 McClelland Drive
Frankston Vic 3199
Country 69580 0
Australia
Phone 69580 0
+61 397890088
Fax 69580 0
+61 397898866
Email 69580 0
david@peninsulaheart.com.au

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
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