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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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Statin-induced myalgia

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Musculoskeletal

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]

Treatment: Drugs

Comparator / control treatment

matching placebo capsule

Control group

Placebo

Outcomes

Primary outcome [1]

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]

3, 6, 9, 12, 15, 18, 21, 24 and 27 weeks post randomisation

Secondary outcome [1]

To record the number of eligible patients screened and number of those consent to participate

Timepoint [1]

27 weeks post randomisation

Secondary outcome [2]

To evaluate the trial drop out rate and reasons for drop out

Timepoint [2]

27 weeks post randomisation

Secondary outcome [3]

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]

6 months post randomisation

Secondary outcome [4]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/10/2016

Actual

3/04/2017

Date of last participant enrolment

Anticipated

5/02/2018

Actual

5/02/2018

Date of last data collection

Anticipated

31/08/2018

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

National Heart Foundation Vanguard Grant

Address [1]

Level 3, 80 William Street, EAST SYDNEY New South Wales 2010

Country [1]

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]

Hospital

Name [1]

Royal Prince Alfred Hospital

Address [1]

Level 11 KGV Building, Missenden Rd
Camperdown
2050 NSW

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District

Ethics committee address [1]

c/- Research Ethics and Governance Office (REGO)
 Royal Prince Alfred Hospital
 Missenden Road
 CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/12/2015

Approval date [1]

18/07/2016

Ethics approval number [1]

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

Dr Nicole Li

Address

The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050

Country

Australia

Phone

+61 2 8052 4507

Fax

+61 2 8052 4502

[email protected]

Contact person for public queries

Name

Nicole Li

Address

The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050

Country

Australia

Phone

+61280524507

Fax

+61 2 8052 4502

[email protected]

Contact person for scientific queries

Name

Nicole Li

Address

The George Institute for Global Health
Level 10 KGV Building
Missenden rd
Camperdown
NSW 2050

Country

Australia

Phone

+61280524507

Fax

+61 2 8052 4502

[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

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Documents added automatically

No additional documents have been identified.

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