A Series of Randomised Controlled N-of 1 Trials in Patients Who Have Discontinued or Are Considering Discontinuing Statin Use Due to Muscle-related Symptoms to Assess if Atorvastatin Treatment Causes More Muscle Symptoms Than Placebo
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 200
- Locations
- 58
- Primary Endpoint
- Muscle Symptoms
Study Overview
Brief Summary
Statins are known to cause rare but serious side effects such as rhabdomyolysis (breakdown of muscle tissue) but many patients stop taking statins due to less severe symptoms, such as muscle pain or fatigue.
This study aims to determine whether symptoms occurring during statin use are caused by statins. The trial will compare patient-reported side effects of statins (20mg atorvastatin) vs. placebo.
Patients will be randomized to alternating treatment blocks of either statin or placebo split into six two-month treatment periods. At the end of each period, patients will be asked to self-report side effects using a website or mobile app.
Detailed Description
- INTRODUCTION Statins reduce cardiovascular disease (CVD) risk and are recommended as part of the treatment strategy for primary and secondary prevention of CVD. Although statins are the most commonly prescribed treatment in the UK, there is uncertainty about adverse effects.
Severe statin adverse effects are rare but there is widespread reporting of less well-defined statin-related symptoms in the media, notably muscle pain and weakness that significantly affect statin users. These reports have been prompted by non-randomised, non-blinded observational studies but have not been confirmed in blinded randomised controlled trials (RCTs). A major limitation of observational studies is lack of blinding: patients taking a medication expect to experience adverse effects and therefore report high levels of symptoms vs. statin-free population. This phenomenon, the "nocebo" effect, leads to bias.
Many patients believe their muscle symptoms are statin related, leading to therapeutic discontinuation. GPs face challenging decision making when patients present statin related symptoms and there is no diagnostic tool to evaluate statin symptom burden.
StatinWISE is a N-of-1 trial and offers patients individual study results. Patients are their own control, and therefore optimal treatment can be established. StatinWISE will address some of the criticisms of previous evidence. 2. TRIAL DESIGN i) Randomised, double blind, placebo controlled N-of-1 trial ii) Patients who have stopped or are considering discontinuation of their statin due to muscle symptoms iii) Once-daily oral administration of Atorvastatin (20mg) or placebo iv) Study treatment is 12-months v) IMP in 2-month treatment periods vi) Quantify the occurrence of self-reported muscle symptoms vii) 200 patients will be recruited.
2.1 RECRUITMENT OF PARTICIPANTS Participants will be recruited directly from GP Practices or by advertising to the public.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double Blinded IMP
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults (aged 16 and over)
- •Prescribed statin treatment in the last 3 years
- •Stopped OR considering stopping statin treatment due to muscle symptoms
- •Provided fully informed consent.
Exclusion Criteria
- •Any previously documented serum alanine aminotransferase (ALT) levels at or above three times the upper limit of normal;
- •Have persistent, generalised, unexplained muscle pain (whether associated or not with statin use) and have creatinine kinase (CK) levels greater than 5 times the upper limit of normal
- •Any contraindications listed in the IMP SPC
- •Should not be using atorvastatin 20mg daily in the opinion of the general practitioner.
Arms & Interventions
Atorvastatin 20mg
Atorvastatin to be taken daily in 2 month treatment periods, 3 treatment periods in 12 months
Intervention: Atorvastatin 20mg (Drug)
Atorvastatin 20mg
Atorvastatin to be taken daily in 2 month treatment periods, 3 treatment periods in 12 months
Intervention: Placebo (Drug)
Placebo - Microcrystalline Cellulose
Placebo to be taken daily in 2 month treatment periods, 3 treatment periods in 12 months
Intervention: Atorvastatin 20mg (Drug)
Placebo - Microcrystalline Cellulose
Placebo to be taken daily in 2 month treatment periods, 3 treatment periods in 12 months
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Muscle Symptoms
Time Frame: Every 8 weeks for 12 months in total
Patient reported muscle symptoms (pain, weakness, tenderness, stiffness or cramp).
Secondary Outcomes
- Patient belief of statin effects, medication adherence(at 15 months post randomisation)