Phase 4
Completed N=60
Self-Assessment Method for Statin Side-effects Or Nocebo
Adverse Effects · Cardiovascular Disease · Hyperlipidemia
Source: ClinicalTrials.gov NCT02668016 ↗
Enrolled (actual)
60
Serious AEs
7.9%
Results posted
Aug 2024
Primary outcomePrimary: Mean Symptom Scores Across Statin, Placebo and no Treatment Periods — 16.3; 15.4; 8.0 units on a scale
◆ Published Evidence
Highly cited
184citations · ~37 / year
Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.
Summary
Front-line clinicians cannot currently test for an individual participant whether symptoms experienced are the pharmacological result of a statin or due to other phenomena. In this trial, participants who have previously ceased statins due to side effects will be offered the opportunity to undergo twelve randomly ordered 1-month periods. There will be four periods of no medication, four periods of placebo and four periods of statin. The placebo and the statin pills will be identical in appearance. Participants will record on a daily basis side-effects experienced. At the end of the study, the one-month sessions are sorted into the order shown above. The participant can then observe directly how much of the increase in symptoms seen with statin is also seen with placebo.
1. Hypothesis 1: that >30% of participants enrolling for the study will complete it.
2. Hypothesis 2: Overall >50% of symptom burden is nocebo rather than pharmacological
3. The investigators will define the Nocebo proportion of side effects.
4. Hypothesis 3: that the majority of participants, at 6 months after completion, will either be taking statins or have declined statins for reasons other than perceived side effects.
Linked Publications
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Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Symptom Scores Across Statin, Placebo and no Treatment Periods |
16.3; 15.4; 8.0 | — |
| SECONDARY Number of Participants Currently Being Prescribed Statins |
30; 0; 0 | — |
| SECONDARY Attribution of Adverse Symptoms |
22; 17; 8; 3; 9; 1 | — |
Eligibility Criteria
Inclusion Criteria
- Aged 18 years or older
- Previously taken one or more statins
- Withdrawn from statins because of perceived side effects
- Developed side effects within 2 weeks of initiation
- Clinical indication for statins for primary or secondary prevention of cardiovascular disease or dyslipidaemia, on either no medication or non-statin lipid lowering therapy (e.g, ezetimibe)
Exclusion Criteria
- History of neuropathy
- Regularly taking prescribed analgesia
- History of a chronic pain condition
- History of severe mental illness (as their experience of symptoms may already be altered)
- Current use of fibrates (because of the risk of interaction with statins; will not exclude participants taking ezetimibe).
- Severe previous reaction or reaction considered immunological, such as anaphylaxis, facial swelling, severe rash, muscle ache with rise in serum creatine kinase, inflammatory myopathy, rhabdomyolysis or liver function abnormalities (aspartate transaminase (AST) or alanine transaminase (ALT) greater than 3 times upper limit or normal).
- Side-effects taking longer than 2 weeks to develop (because in such participants much longer blocks of treatment would be required; if the present study is positive such studies will be planned for the future).
- History of statin intolerance with drug interaction to antiretroviral drugs.
- Currently taking antiretrovirals with known interaction to statins
- Currently taking any drug other than antiretrovirals with known interaction to statins
- Side effects taking longer than 2 weeks to present.
- In clinical judgement of study doctor, participant should not participate.
Data sourced from ClinicalTrials.gov (NCT02668016) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.