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

• ClinicalTrials.gov Identifier: NCT02099123
• Recruitment Status: Active, not recruiting
• First Posted: March 28, 2014
• Last Update Posted: March 6, 2023
• Sponsor: Monash University
• Collaborators: National Health and Medical Research Council, Australia; National Heart Foundation, Australia
• Information provided by (Responsible Party): Sophia Zoungas, Monash University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Independent Living; Disability Free Survival; Elderly; Healthy	Drug: Atorvastatin; Drug: Placebo (for Atorvastatin)	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9971 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Study of STAtins for Reducing Events in the Elderly (STAREE)
• Study Start Date: July 2015
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atorvastatin; 40 mg atorvastatin (2 x 20 mg atorvastatin), taken orally once daily	Drug: Atorvastatin; Atorvastatin 20 mg tablet; Other Names: Lipitor, , , Cadivast, Caduet, Lorstat, Torvastat, Trovas; Atorachol; Cadatin
Placebo Comparator: Placebo; Placebo (2 x 20 mg placebo) taken orally once daily	Drug: Placebo (for Atorvastatin); Inactive pill manufactured to mimic Atorvastatin 20 mg tablet; Other Name: no other names

Outcome Measures

Primary Outcome Measures :

1. Disability free survival - death or development of dementia or development of persistent physical disability [ Time Frame: 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. ]
   Defined as survival free of dementia or persistent physical disability (as derived from the endpoints of all-cause mortality, dementia and physical disability)
2. Major cardiovascular events [ Time Frame: 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. ]
   Defined as the first occurrence of a non-fatal myocardial infarction, non-fatal stroke or cardiovascular death

Secondary Outcome Measures :

1. Cardiovascular death [ Time Frame: 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 cardiovascular events
2. Fatal and Non-fatal Mycocardial infarction [ Time Frame: 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
3. Hospitalisations [ Time Frame: 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. ]
   Hospitalisation reasons and length of stay
4. Fatal and Non-fatal Cancer [ Time Frame: 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 (excluding non-melanoma skin cancer)
5. Other cognitive impairment [ Time Frame: 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. ]
   Cognitive decline as assessed using cognitive tests excluding depression
6. Quality of life measured by the Short Form Health Survey (SF-36) [ Time Frame: 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) administered at every second year of follow-up).
7. Cost-effectiveness of statin [ Time Frame: 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
8. Fatal and Non-fatal Stroke [ Time Frame: 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 can be a) haemorrhagic or b) thromboembolic
9. Approved need for permanent residential care [ Time Frame: 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. ]
   ACAS report
10. Dementia [ Time Frame: 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 dementia (COWAT, Stroop test, Trail Making Test, HVLT-R, SDMT, ADAS-Cog, Lurian overlapping figures) or external diagnosis
11. Persistent physical disability [ Time Frame: 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. ]
    KATZ-ADL administered every 6 months or external diagnosis
12. All cause death [ Time Frame: 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
13. Heart failure [ Time Frame: 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
14. Atrial fibrillation [ Time Frame: 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
15. Revascularisation procedure [ Time Frame: 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

Other Outcome Measures:

1. New onset diabetes [ Time Frame: 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. ]
   New diagnosis of diabetes

Eligibility Criteria

• Ages Eligible for Study: 70 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Australia, Tasmania

Tasmania

Hobart, Tasmania, Australia

Australia, Victoria

Victoria

Melbourne, Victoria, Australia

Australia, Western Australia

South Australia

Adelaide, Western Australia, Australia

Australia

Queensland

Brisbane, Australia

New South Wales

Newcastle, Australia

Western Australia

Perth, Australia

Sponsors and Collaborators

Monash University

National Health and Medical Research Council, Australia

National Heart Foundation, Australia

Investigators

• Principal Investigator: Sophia Zoungas, MBBS, FRACP; Monash University

More Information

• Responsible Party: Sophia Zoungas, Professor Sophia Zoungas, Monash University
• ClinicalTrials.gov Identifier: NCT02099123
• Other Study ID Numbers: NHMRC 1068146
• First Posted: March 28, 2014
• Last Update Posted: March 6, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: On completion of the trial, and after publication of the primary and secondary outcomes of the study, requests for access to de-identified data (to be provided through a secure online environment) may be submitted to the researchers located at the School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sophia Zoungas, Monash University:

Survival; Functional Disability; Cardiovascular Disease; Diabetes; Dementia; Cancer

Additional relevant MeSH terms:

Atorvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors