A Clinical Trial of STAtin Therapy for Reducing Events in the Elderly (STAREE)

Study Overview
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Brief Summary
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The STAREE study will examine whether treatment with statin (atorvastatin 40mg) compared with placebo will prolong disability free survival and reduce major cardiovascular events amongst healthy elderly people (≥70 years).

Detailed Description
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Statin therapy has been shown to reduce the risk of vascular events in younger individuals with manifest atherosclerotic disease or at high risk of vascular events. However, data derived from meta-analyses of existing trials suggests that the efficacy of statins may decline sharply amongst those over 70-75 years of age. Insufficient patients of this age group have been included in major trials to be certain of the benefit. Within this age group part of the benefit of statin therapy may be offset by adverse effects including myopathy, development of diabetes, cancer and cognitive impairment, all of which are more prevalent in the elderly in any event. The use of statins in the over 70 age group raises fundamental questions about the purpose of preventive drug therapy in this age group. When a preventive agent is used in the context of competing mortality, polypharmacy and a higher incidence of adverse effects its use should be justified by an improvement in quality of life or some other composite measure that demonstrates that the benefit outweighs other factors. STAREE will determine whether taking daily statin therapy (40 mg atorvastatin) will extend the length of a disability-free life, determined from survival outside permanent residential care, in healthy participants aged 70 years and above.

Official Title
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A Study of STAtins for Reducing Events in the Elderly (STAREE)

Conditions
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Independent Living, Disability Free Survival, Elderly, Healthy

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo (for Atorvastatin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged ≥70 years living independently in the community Willing and able to provide informed consent and accept the study requirements (Note: competent physical ability to participate in the trial is assessed using the KATZ ADL questionnaire) Exclusion Criteria: A history of cardiovascular disease (defined as myocardial infarction, stroke, peripheral vascular disease, angina, transient ischaemic attack, coronary artery angioplasty and/or stenting, coronary artery bypass grafting, carotid stenosis, abdominal aortic aneurysm or heart failure), A history of dementia or a 3MS score <78 on screening, A history of diabetes, Total cholesterol >7.5 mmol/L, Moderate or severe chronic kidney disease (persistent proteinuria (Urine albumin:creatinine ratio >30mg/mmol or Urine protein:creatinine ratios >45 mg/mmol)45 and/or eGFR <45ml/min/1.73m2), Moderate or severe liver disease (persistent elevations of transaminases of more than 3 times the upper limit of the normal laboratory reference range), Serious inter-current illness likely to cause death within the next 5 years such as terminal cancer or obstructive airways disease, Current participation in a clinical trial, Absolute contraindication to statin therapy, Current use of statin therapy or other lipid lowering therapy for primary prevention and unwilling to stop therapy, Current long term or permanent use of the following cytochrome P450 (CYP) 3A4 inhibitors : Amiodarone, Boceprevir, Cimetidine, Cyclosporin, Danazol, Fosamprenavir, Indinavir, Lopinavir + Ritonavir, Erythromycin, Fluconazole, Itraconazole, Ketoconazole.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>40 mg atorvastatin (2 x 20 mg atorvastatin), taken orally once daily | Drug: Atorvastatin<br>* Atorvastatin 20 mg tablet<br>* Other names: Cadatin;|
| Placebo Comparator: Placebo<br>Placebo (2 x 20 mg placebo) taken orally once daily | Drug: Placebo (for Atorvastatin)<br>* Inactive pill manufactured to mimic Atorvastatin 20 mg tablet<br>* Other names: no other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability free survival - death or development of dementia or development of persistent physical disability | Defined as survival free of dementia or persistent physical disability (as derived from the endpoints of all-cause mortality, dementia and physical disability) | Time from randomisation to a primary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Major cardiovascular events | Defined as the first occurrence of a non-fatal myocardial infarction, non-fatal stroke or cardiovascular death | Time from randomisation to a primary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Fatal cardiovascular events | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Fatal and Non-fatal Mycocardial infarction | Fatal and non-fatal | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Hospitalisations | Hospitalisation reasons and length of stay | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Fatal and Non-fatal Cancer | Fatal and Non-fatal Cancer (excluding non-melanoma skin cancer) | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Other cognitive impairment | Cognitive decline as assessed using cognitive tests excluding depression | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Quality of life measured by the Short Form Health Survey (SF-36) | Quality of life (measured by the Short Form Health Survey (SF-36) administered at every second year of follow-up). | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Cost-effectiveness of statin | Cost-effectiveness of statin | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Fatal and Non-fatal Stroke | Fatal and Non-fatal Stroke can be a) haemorrhagic or b) thromboembolic | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Approved need for permanent residential care | ACAS report | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Dementia | All-cause dementia (COWAT, Stroop test, Trail Making Test, HVLT-R, SDMT, ADAS-Cog, Lurian overlapping figures) or external diagnosis | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Persistent physical disability | KATZ-ADL administered every 6 months or external diagnosis | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| All cause death | All cause death | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Heart failure | Heart failure | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Atrial fibrillation | Atrial fibrillation | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 
| Revascularisation procedure | Revascularisation procedure | Time from randomisation to a secondary endpoint or censoring at the end of study follow-up which is anticipated to be an average 6 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Survival, Functional Disability, Cardiovascular Disease, Diabetes, Dementia, Cancer