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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy; Elderly; Independent Living; Disability Free Survival
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo (for Atorvastatin)

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 Type: Interventional
• Enrollment (Actual): 9971
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sophia Zoungas, MBBS, FRACP; Phone Number: +61 1800 770 664; Email: staree@monash.edu

Study Locations

• Australia
  • Brisbane, Australia
    • Queensland
  • Newcastle, Australia
    • New South Wales
  • Perth, Australia
    • Western Australia
  • Tasmania
    • Hobart, Tasmania, Australia
      • Tasmania
  • Victoria
    • Melbourne, Victoria, Australia
      • Victoria
  • Western Australia
    • Adelaide, Western Australia, Australia
      • South Australia

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: no other names

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New onset diabetes	New diagnosis of diabetes	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.

Collaborators and Investigators

• Sponsor: Monash University
• Collaborators: National Health and Medical Research Council, Australia; National Heart Foundation, Australia
• Investigators: Principal Investigator: Sophia Zoungas, MBBS, FRACP, Monash University

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Cancer; Survival; Cardiovascular Disease; Dementia; Functional Disability
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: NHMRC 1068146

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No