Study protocol for statin web-based investigation of side effects (StatinWISE): a series of randomised controlled N-of-1 trials comparing atorvastatin and placebo in UK primary care

TY - JOUR

T1 - Study protocol for statin web-based investigation of side effects (StatinWISE)

T2 - a series of randomised controlled N-of-1 trials comparing atorvastatin and placebo in UK primary care

AU - Herrett, Emily

AU - Williamson, Elizabeth

AU - Beaumont, Danielle

AU - Prowse, Danielle

AU - Youssouf, Nabila

AU - Brack, Kieran

AU - Armitage, Jane

AU - Goldacre, Ben

AU - MacDonald, Thomas

AU - Staa, Tjeerd van

AU - Roberts, Ian

AU - Shakur-Still, Haleema

AU - Smeeth, Liam

N1 - The research is funded by the National Institute for Health Research – Health Technology Programme (reference 14/49/159). The study is sponsored by the London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT. The study is registered at controlled-trials.com ISRCTN30952488, August 2016, ClinicalTrials.gov with reference NCT02781064 and EUDRACT 2016-000141-31.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Introduction: Statins are effective at preventing cardiovascular disease, widely prescribed and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals.Methods and analysis: This series of 200 randomised, double-blinded N-of-1 trials in primary care will determine (1) the effect of statins on all muscle symptoms and (2) the effect of statins on muscle pain that is perceived to be statin related. Patients who are considering discontinuing statin use due to muscle symptoms and those who have discontinued in the last 3 years due to such symptoms will be recruited. Participants will be randomised to a sequence of six 2-month treatment periods during which they will receive atorvastatin 20 mg per day or matched placebo. On each of the last 7 days of each treatment period, participants will rate their muscle symptoms on a Visual Analogue Scale (VAS).At the end of their trial, participants will be shown numerical and graphical summaries of their own symptom data during statin and placebo periods. The primary analysis on the aggregate data from all participants will be a linear mixed model for VAS muscle symptom score, comparing scores during treatment with statin and placebo.Ethics and dissemination: This trial received a favourable opinion from South Central-Hampshire A Research Ethics Committee. Results will be published in a peer-reviewed medical journal. Dissemination of results to patients will take place via the media, website (statinwise.lshtm.ac.uk) and patient organisations.Trial registration number: ISRCTN30952488.

AB - Introduction: Statins are effective at preventing cardiovascular disease, widely prescribed and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals.Methods and analysis: This series of 200 randomised, double-blinded N-of-1 trials in primary care will determine (1) the effect of statins on all muscle symptoms and (2) the effect of statins on muscle pain that is perceived to be statin related. Patients who are considering discontinuing statin use due to muscle symptoms and those who have discontinued in the last 3 years due to such symptoms will be recruited. Participants will be randomised to a sequence of six 2-month treatment periods during which they will receive atorvastatin 20 mg per day or matched placebo. On each of the last 7 days of each treatment period, participants will rate their muscle symptoms on a Visual Analogue Scale (VAS).At the end of their trial, participants will be shown numerical and graphical summaries of their own symptom data during statin and placebo periods. The primary analysis on the aggregate data from all participants will be a linear mixed model for VAS muscle symptom score, comparing scores during treatment with statin and placebo.Ethics and dissemination: This trial received a favourable opinion from South Central-Hampshire A Research Ethics Committee. Results will be published in a peer-reviewed medical journal. Dissemination of results to patients will take place via the media, website (statinwise.lshtm.ac.uk) and patient organisations.Trial registration number: ISRCTN30952488.

KW - adverse events

KW - N-of-1 trial

KW - statin

U2 - 10.1136/bmjopen-2017-016604

DO - 10.1136/bmjopen-2017-016604

M3 - Article

C2 - 29197834

SN - 2044-6055

VL - 7

SP - 1

EP - 8

JO - BMJ Open

JF - BMJ Open

IS - 12

M1 - e016604

ER -