StatinWISE

Full title A SERIES OF RANDOMISED CONTROLLED N-of 1 TRIALS IN PATIENTS WHO HAVE DISCONTINUED OR WISH TO DISCONTINUE STATIN USE DUE TO MUSCLE-RELATED SYMPTOMS TO ASSESS IF ATORVASTATIN TREATMENT CAUSES MORE MUSCLE SYMPTOMS THAN PLACEBO
Research type Research study
IRAS ID 197990
Contact Name Liam Smeeth
Contact Email liam.smeeth@lshtm.ac.uk
Sponsor organisation London School of Hygiene and Tropical Medicine
Eudract number 2016-000141-31
ISRCTN number ISRCTN30952488
Clinicaltrials.gov identifier NCT02781064
Additional reference number fields
Research summary Cholesterol is essential for the body to work well, but too much ‘bad cholesterol’ (called low-density lipoprotein or LDL) is unhealthy. High levels of ‘bad cholesterol’ in the blood can lead to fatty deposits building up in our arteries. This can increase the risk of developing cardiovascular disease, which includes conditions such as coronary heart disease (leading to angina and heart attack) and stroke. Statins are drugs that are used to reduce the amount of ‘bad cholesterol’ the body makes while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL). Statins are the most commonly prescribed treatment in the UK. Recently, the number of people eligible to receive statins increased by over 2 million due to updated National Institute for Health and Care Excellence recommendations. 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. Trials have not found any differences between those taking statins and those taking placebo in terms of these less severe muscle symptoms, but some have questioned whether the information collected was adequate. Given that it is known that statins can reduce heart attacks and strokes, it would be helpful to know how frequently the symptoms experienced during statin use are related to the statin and how frequently related to other causes. This will help inform patients’ and doctors’ treatment choices. We propose a trial which will look at side effects of atorvastatin compared to a matching placebo. We will recruit 200 patients who have recently stopped or wish to stop taking statins due to unwanted muscle symptoms. Patients will be recruited through general practices. Each patient will be in the study for one year, split into six two-month treatment periods. Patients will be allocated to a sequence of statin and placebo tablets/capsules. This will allow each patient to acts as their own control, so at the end of the trial, they will be able to compare their own level of symptoms between the statin and placebo treatment periods and use this information to help decide the best treatment options. This is called an ‘N-of’1’ trial. Two months is sufficient for short-term side effects to emerge, and the trial’s one year duration is brief enough to minimise any adverse impact on cardiovascular outcomes from under-treatment. There will be no wash-out period, but symptoms will be measured at the end of each treatment period to ensure that they reflect the current treatment. At the end of each two-month period, patients will be asked to submit symptom information using a specially-designed mobile app; outcomes will be self-reported side effects on a visual sliding 0-100 scale for muscle symptoms. If patients are unable to use the mobile app, data can be submitted directly online by the patient or answers to the outcome questions obtained by a researcher through a telephone call. Patients are free to choose a suitable method of follow-up. Patients will be reminded to submit symptom information prior to each data collection period. This will be done by email, text, and phone calls. At the end of the trial, patients will be shown summaries of their individual results, which will help them to decide whether to continue taking statins. Symptom reports will be collected at 3 months afterwards to assess whether this information impacts subsequent treatment choices and symptom severity. We will combine the results from each individual to assess how frequently statins are causing side effects in people who perceive themselves to be intolerant. As part of the trial we will ask patients to provide a blood sample for an optional genetic analysis as part of a larger collaborative effort investigating genetic associations with statins effects. Specific results will not be fed back to clinicians or to patients.
REC Name South Central - Hampshire A Research Ethics Committee
REC Reference 16/SC/0324
REC Opinion

Favourable Opinion

Favourable Opinion

Date of REC Opinion 27 June 2016