N-of-1 trials for possible statin-induced myalgia

Aim: The objective of the study is to evaluate the feasibility and sustainability of introducing an N-of-1 trial clinical service to improve the diagnosis of statin-induced myalgia in Australian clinical setting. More specifically, the primary study aim is to evaluate the value of N-of-1 trials in determining statin induced myalgia by comparing measures of myalgia (the myalgia score, CK levels and other measures of pain scores) in treatment versus control periods.

Method: 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, FGF-21 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. The primary outcome will be the myalgia score ranging from 0 to 10. Secondary outcomes include serum CK level, pain severity scores, FGF-21 level and genotype. We will also report the overall rates of lipids, compliance to the trial requirements, reason for drop out, proportion that are diagnosed at the end of the trial to have statin-related myalgia, statin therapy resumption rate,  and cost for running N-of-1 trial among these participants.

This study is funded by a Vanguard Grant from the National Heart Foundation of Australia.