Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000732886
Ethics application status
Approved
Date submitted
9/07/2012
Date registered
9/07/2012
Date last updated
9/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Rosuvastatin versus Protease Inhibitor Switching for Hypercholesterolaemia in HIV-infected Adults.
Scientific title
To compare the effects of rosuvastatin (10 mg daily) and ritonavir-boosted protease inhibitor switching on the fasting total cholesterol of treatment-experienced HIV-infected adults over 12 weeks.
Secondary ID [1] 280808 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
SoS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolaemia associated with ritonavir-boosted protease inhibitor therapy in of HIV-infected adults 286867 0
Condition category
Condition code
Infection 287191 287191 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Cardiovascular 287193 287193 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Rosuvastatin tablets, dose 10 mg daily (5 mg daily in Asian participants), taken once daily for 12 weeks. Participants assigned to this intervention will continue ritonavir-boosted anti-retroviral therapy.
Intervention code [1] 285236 0
Treatment: Drugs
Comparator / control treatment
Switching of ritonavir-boosted protease inhibitor to an alternative anti-retroviral agent as part of combination anti-retroviral therapy for HIV-1 infection.

Valid switch options are based on the U.S Department of Health and Human Services anti-retroviral guidelines in adolescents and adults, and include nevirapine tablets (400 mg daily), rilpivirine tablets (25 mg daily), raltegravir tablets (400 mg twice daily) and unboosted atazanavir tablets (400 mg daily). Final decisions regarding switch medication will be made by the treating physician, but will be for a duration of 12 weeks
Control group
Active

Outcomes
Primary outcome [1] 287483 0
To compare the effects of rosuvastatin to switching of ritonavir-boosted protease inhibitor to an alternate anti-retroviral agent on the fasting total cholesterol over 12 weeks in treatment-experienced HIV-infected adults.
Timepoint [1] 287483 0
Screening visit blood testing to assess for study eligibility
Baseline visit blood testing (Week 0)
Week 4 visit blood testing to assess change from baseline
Week 12 visit blood testing to assess change from baseline
Secondary outcome [1] 298263 0
Safety parameters (includes HIV-1 RNA level, clinical adverse events, serious adverse events, laboratory adverse events, modifications to anti-retroviral therapy)

Clinical adverse events (for example, skin rashes) or laboratory events (for example, elevated liver enzymes) occurring during the study will be clinically assessed. Any adverse events ongoing at Week 12 deemed related to study drug by an investigator will be followed up for at least 30 days, or until resolution. Additional unscheduled visits and pathology tests may be required as part of this follow-up.
Timepoint [1] 298263 0
Baseline (Week 0)
Week 4 visit
Week 12 visit
Secondary outcome [2] 298264 0
Quality of life (assessed via the SF-12 survey)
Timepoint [2] 298264 0
Baseline (Week 0)
Week 4 visit
Week 12 visit
Secondary outcome [3] 298265 0
Fasting HDL/LDL cholesterol, LDL particle size, triglycerides and total:HDL cholesterol, D-dimer, C-reactive protein, fasting glucose and insulin
Timepoint [3] 298265 0
Baseline (Week 0)
Week 4 visit
Week 12 visit
Secondary outcome [4] 298266 0
Calculated cardiovascular risk scores (Framingham and D:A:D)
Timepoint [4] 298266 0
Screening visit
Week 12 visit

Eligibility
Key inclusion criteria
1. HIV-positive status
2. Adults (>=18 years of age)
3. Stable and well-tolerated combination ART including a ritonavir-boosted PI for the previous 6 months
4. HIV RNA <50 copies/mL for at least the preceding 3 months
5. Fasting total cholesterol >5.5 mmol/L (>213 mg/dL)
6. Framingham risk score >=8% at 10 years OR diabetes mellitus OR a family history of premature coronary artery disease in a first-degree relative
7. Provision of written, informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
8. Any statin in the previous 12 weeks
9. Previous statin-induced myopathy or hepatitis
10. History of coronary artery disease, stroke or any other indication for the use of statin therapy (hyperlipidaemia: genetic, secondary or idiopathic)
11. Concurrent use of:
a). oral corticosteroids use other than for replacement therapy (ie. prednisolone 5-7.5 mg, hydrocortisone 20-30 mg, cortisone acetate 25-37.5 mg daily)
b). other immunosuppressive or immunomodulating drugs
12. Contra-indication to rosuvastatin therapy:
a). liver transaminases >5 times the upper normal limit
b). creatinine clearance <30 mL/min
c). known myopathy
d). current fibrate therapy
e). known resistance to one or more “backbone” ART drugs
13. No potent switch ART drug available to replace the current ritonavir-boosted PI
14. Known intolerance to rosuvastatin or the proposed switch ART drug
15. Women attempting or likely to become pregnant, or who are pregnant or breast-feeding
16. A patient with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study
17. Unable to complete study procedures.

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)
This is a randomized, open-label, 12-week prospective trial. Sixty (60) eligible subjects will be randomly allocated 1:1 to either:
(A) switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator; OR
(B) continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be stratified by baseline protease inhibitor type and by baseline total cholesterol (>7.0 mmol/L or <=7.0 mmol/L [275 mg/dL]). Randomisation within each stratum will be performed by St. Vincent's Centre for Applied Medical Research staff otherwise not involved in the study. A computerized random number generator will be used to produce a random order of interventions.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/07/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 5499 0
2010
Recruitment postcode(s) [2] 5500 0
3004
Recruitment postcode(s) [3] 5501 0
3068
Recruitment postcode(s) [4] 5502 0
3181
Recruitment postcode(s) [5] 5503 0
3182

Funding & Sponsors
Funding source category [1] 285600 0
Self funded/Unfunded
Name [1] 285600 0
Country [1] 285600 0
Primary sponsor type
Hospital
Name
St. Vincent's Hospital, Sydney
Address
390 Victoria Street, Darlinghurst, New South Wales, 2010
Country
Australia
Secondary sponsor category [1] 284433 0
None
Name [1] 284433 0
Address [1] 284433 0
Country [1] 284433 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287602 0
St. Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 287602 0
Ethics committee country [1] 287602 0
Australia
Date submitted for ethics approval [1] 287602 0
21/11/2011
Approval date [1] 287602 0
24/01/2012
Ethics approval number [1] 287602 0
HREC/11/SVH/194

Summary
Brief summary
To compare the effects of adding rosuvastatin to switching of ritonavir-boosted protease inhibitor on total cholesterol levels in HIV-infected adults with increased cardiovascular risk profiles over a 12-week period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34415 0
Address 34415 0
Country 34415 0
Phone 34415 0
Fax 34415 0
Email 34415 0
Contact person for public queries
Name 17662 0
Nicola Mackenzie
Address 17662 0
St. Vincent's Centre for Applied Medical Research
Clinical Research Program
St. Vincent's Hospital
Level 4, Xavier Building
390 Victoria Street
Darlinghurst, New South Wales, 2010
Country 17662 0
Australia
Phone 17662 0
+61 2 83822919
Fax 17662 0
+61 2 83823869
Email 17662 0
[email protected]
Contact person for scientific queries
Name 8590 0
Professor Andrew Carr
Address 8590 0
St. Vincent's Centre for Applied Medical Research
Clinical Research Program
St. Vincent's Hospital
Level 4, Xavier Building
390 Victoria Street
Darlinghurst, New South Wales, 2010
Country 8590 0
Australia
Phone 8590 0
+61 2 83823359
Fax 8590 0
+61 2 83822090
Email 8590 0
[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
SourceTitleYear of PublicationDOI
EmbaseRosuvastatin vs. protease inhibitor switching for hypercholesterolaemia: a randomized trial.2016https://dx.doi.org/10.1111/hiv.12362
N.B. These documents automatically identified may not have been verified by the study sponsor.