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Trial registered on ANZCTR


Registration number
ACTRN12616001168448
Ethics application status
Approved
Date submitted
19/08/2016
Date registered
26/08/2016
Date last updated
10/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to determine whether myalgia is due to statin use
Scientific title
Protocol for a N-of-1 (Single-Patient) trial service to determine whether myalgia is due to statin use in a sample of patients with a history of statin-induced myalgia
Secondary ID [1] 289307 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Statin-induced myalgia 298902 0
Condition category
Condition code
Cardiovascular 298978 298978 0 0
Other cardiovascular diseases
Musculoskeletal 299900 299900 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Rosuvastatin 5mg once daily for 3 weeks followed by a “wash-out period” with a matching placebo for 3 weeks, and followed by matching placebo 3 weeks. Oral capsules
Intervention code [1] 295664 0
Treatment: Drugs
Comparator / control treatment
matching placebo capsule
Control group
Placebo

Outcomes
Primary outcome [1] 299339 0
To evaluate the value of N-of-1 trials in determining statin induced myalgia by comparing measures of myalgia (through the Myalgia Score questionnaire, and CK levels in serum assay) in treatment versus control periods.
Timepoint [1] 299339 0
3, 6, 9, 12, 15, 18, 21, 24 and 27 weeks post randomisation
Secondary outcome [1] 326886 0
To record the number of eligible patients screened and number of those consent to participate
Timepoint [1] 326886 0
27 weeks post randomisation
Secondary outcome [2] 326887 0
To evaluate the trial drop out rate and reasons for drop out

Timepoint [2] 326887 0
27 weeks post randomisation
Secondary outcome [3] 326888 0
To evaluate resume rate to statin therapy after completion of N-of-1 trials
the number of participants that will continue statin therapy after completion of the study
Timepoint [3] 326888 0
6 months post randomisation
Secondary outcome [4] 326889 0
The percentage of participants that are given a final diagnosis of statin-related myalgia at the conclusion of their participation in the N-of-1 service
Timepoint [4] 326889 0
27 weeks post randomisation

Eligibility
Key inclusion criteria
Has indication for statin therapy;
History of intolerance of both atorvastatin 10 mg AND rosuvastatin 5 mg monotherapy;
History of statin-related myalgia occuring within three weeks of starting statin therapy and consequently discontinued statin use;
Without clinically significant CK elevations, <3x the upper limit of normal or <3x times the baseline value
Willing to restart statin therapy.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy;
History of alcohol and/or drug abuse;
Hypothyroidism;
Renal function impairment;
Liver obstructions, patients with elevated liver enzymes (up to 3 times)
History of rhabdomyolysis;
History of metabolic or inflammatory myopathy;
History of neuropathy;
Unlikely to comply with the demands of N-of-1 trial.

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)
Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Other
Other design features
N-of-1 single patient design
Phase
Phase 4
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6505 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 14069 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 294341 0
Charities/Societies/Foundations
Name [1] 294341 0
National Heart Foundation Vanguard Grant
Address [1] 294341 0
Level 3, 80 William Street, EAST SYDNEY New South Wales 2010
Country [1] 294341 0
Australia
Primary sponsor type
Other
Name
The George Institue for Global Health
Address
Level 10, King George V Building Missenden Rd, Camperdown NSW 2050
Postal Address: PO Box: M201 Missenden Rd, NSW 2050
Country
Australia
Secondary sponsor category [1] 293180 0
Hospital
Name [1] 293180 0
Royal Prince Alfred Hospital
Address [1] 293180 0
Level 11 KGV Building, Missenden Rd
Camperdown
2050 NSW
Country [1] 293180 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295759 0
Sydney Local Health District
Ethics committee address [1] 295759 0
c/- Research Ethics and Governance Office (REGO)
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 295759 0
Australia
Date submitted for ethics approval [1] 295759 0
09/12/2015
Approval date [1] 295759 0
18/07/2016
Ethics approval number [1] 295759 0
X15-0411

Summary
Brief summary
National Heart Foundation guidelines recommend long-term statin therapy in several major patient groups, but adherence rates are low, even following life-threatening events such as acute coronary syndrome. Muscle-related symptoms are the most commonly reported reason for statin discontinuation and about 1 in 5 patients taking statins report some degree of muscular pain. Placebo-controlled trials indicate overall in a treated population most symptoms are not due to the statin, but for an individual patient it is typically impossible to be certain. N-of-1 (single-patient multiple crossover) trials offer a simple, intuitive way to resolve this uncertainty. While N-of-1 trials have been used for more than 20 years, to date, few clinical services in Australia are conducting N-of-1 trials on a regular basis to improve the management of individual patient. Fewer studies have looked at the potential of using N-of-1 trials to determine statin tolerability. A recently published study suggested that N-of-1 trials can improve the assessment of statin-related myalgia in selected patients from endocrinology clinics in Canada. However, the results were limited by its small sample size and the potential for expanded use of N-of-1 trials to improve the compliance of statin therapy among statin intolerant patients remains unclear.
The study will include up to 15 N-of-1 trial participants. Patients with prior history of intolerance of both atorvastatin 10 mg AND rosuvastatin 5 mg monotherapy, had statin-related myalgia occurring within three weeks of starting statin therapy and consequently discontinued statin use will be invited to participate. Each person will go through 3 double-blind, crossover comparisons of statin versus matching placebo. Each treatment and control period will last for 3-weeks and there will be a 3-week placebo wash out period after each of the active statin treatment. The total trial period for each participant will be 27 weeks. Myalgia scores will be recorded on a weekly basis during the study period. Brief Pain Inventory Questionnaire will be completed and blood sample collection will be done at baseline and at the end of each active treatment and control period to measure serum CK, ALT, AST, FGF21 and creatinine levels. To avoid unblinding of treatment allocation during the trial period, additional blood samples will be stored to measure lipids’ levels upon study completion. Genotype analysis will also be done at the end of the study to determine if genotype is associated with statin-induced myalgia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66202 0
Dr Nicole Li
Address 66202 0
The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050
Country 66202 0
Australia
Phone 66202 0
+61 2 8052 4507
Fax 66202 0
+61 2 8052 4502
Email 66202 0
nli@georgeinstitute.org.au
Contact person for public queries
Name 66203 0
Dr Nicole Li
Address 66203 0
The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050
Country 66203 0
Australia
Phone 66203 0
+61280524507
Fax 66203 0
+61 2 8052 4502
Email 66203 0
nli@georgeinstitute.org.au
Contact person for scientific queries
Name 66204 0
Dr Nicole Li
Address 66204 0
The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050
Country 66204 0
Australia
Phone 66204 0
+61280524507
Fax 66204 0
+61 2 8052 4502
Email 66204 0
nli@georgeinstitute.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary