Condition category
Circulatory System
Date applied
13/06/2013
Date assigned
21/06/2013
Last edited
03/04/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Research in younger people has shown that high levels of cholesterol, especially LDL cholesterol (commonly referred to as bad cholesterol), are associated with increased risks of heart attacks and death due to heart disease. Clinical trials have also shown that reduction of cholesterol levels with drugs called statins reduces the risk of heart attack and death due to heart disease. In fact, these trials have also reduced the risk of stroke. However in older people the link between raised cholesterol and increased risk disappears, raising the question as to whether lowering cholesterol in older people will be beneficial. The aim of the PROSPER trial was to investigate this question.

Who can participate?
The study aimed to recruit men and women aged 70-82 years, in Scotland, Ireland and the Netherlands, who had a history of heart disease, stroke or other vascular problems, or were at increased risk because the had diabetes, high blood pressure or were current smokers. The study aimed to recruit 5500 participants.

What does the study involve?
The participants were randomly allocated to two groups, half received treatment with a cholesterol lowering drug called pravastatin (taken as a 40mg tablet once per day) and half with a dummy tablet with no effect on cholesterol. The objective was to reduce the risk of deaths due to heart disease and stroke and to reduce non-fatal heart attacks and strokes. Participants attended screening visits before randomisation and then attended study visits every three months to have study medication issued and to have study data recorded. Blood samples were taken every six months to measure cholesterol levels.

What are the possible benefits and risks of participating?
The potential benefits to participants in the study were regular health assessments during the trial, the possible reduction in risk of cardiovascular events in the pravastatin treated group. Potential risks to participants in the pravastatin treated group were minor abnormalities in liver function tests and in some cases increased risk of muscle pain as reported in previous statin trials.

Where is the study run from?
The trial was run from co-ordinating centres in Glasgow, Cork and Leiden with the main co-ordinating centre at the Glasgow Royal Infirmary and the study data centre at the Robertson Centre for Biostatistics in Glasgow.

When is the study starting and how long is it expected to run for?
The study started in December 1997 and finished in November 2002.

Who is funding the study?
The study was funded by Bristol Meyer's Squibb.

Who is the main contact?
Professor Ian Ford
University of Glasgow

Trial website

Contact information

Type

Scientific

Primary contact

Prof Ian Ford

ORCID ID

Contact details

Robertson Centre for Biostatistics
University of Glasgow
Level 11 Boyd Orr Building
University Avenue
Glasgow
G12 8QQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CV123-166

Study information

Scientific title

A multicentre, randomised, double-blind, placebo controlled trial to evaluate the efficacy of pravastatin for the prevention of vascular events in the elderly

Acronym

PROSPER

Study hypothesis

The objective of this trial is to examine the hypothesis that pravastatin 40mg will reduce cardiovascular and cerebrovascular events in elderly subjects with vascular disease or who are at high risk for vascular disease.

Ethics approval

Ethics approval was obtained from the following committees:
Greater Glasgow Community/Primary Care Local Research Ethics Committee
Dumfries and Galloway Health Board Local Research Ethics Committee
Argyll and Clyde Health Board Local Research Ethics Committee (reference LREC 85/97)
Lanarkshire Research Ethics Committee (reference ER/9/97/37).
Research Ethics Committee of the Cork Teaching Hospitals (CREC).
Medical Ethical Committee (METc) of the Leiden University Medical Center.

Study design

Multicentre double-blind placebo-controlled randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Cardiovascular disease

Intervention

Pravastatin 40mg or matching placebo tablets to be taking orally once per day throughout the period of follow-up. Because of the expected two year period of recruitment and variable follow-up, treatment was expected to be for a maximum period of just over four years.

Intervention type

Drug

Phase

Not Applicable

Drug names

Pravastatin

Primary outcome measures

The primary outcome measure was the combined endpoint of coronary heart disease (CHD) death (definite plus suspect), nonfatal myocardial infarction (definite plus suspect), and fatal plus nonfatal stroke.

Secondary analyses was performed for the primary endpoint in the following subgroups:
1. Men
2. Women
3. Subjects with or without evidence of previous vascular disease defined as stable angina or intermittent claudication; or stroke, transient ischemic attack (TIA), myocardial infarction (MI), arterial surgery, or amputation for vascular disease prior to study entry, but who are considered to be at high risk on the basis of smoking history, diabetes or hypertension.
4. Subjects with previous vascular disease including stable angina or intermittent claudication; or stroke, transient ischemic attack (TIA), myocardial infarction (MI), arterial surgery, or amputation for vascular disease more than 6 months prior to study entry.

All analyses were carried out on a time to first event basis with analysis censored at end of follow-up, death from other causes or withdrawal of consent. Outcomes could occur continuously throughout the study.

Secondary outcome measures

Secondary outcome measures are:
1. Fatal plus nonfatal stroke
2. Coronary events: definite plus suspect CHD death, definite plus suspect nonfatal MI

Overall trial start date

01/12/1997

Overall trial end date

30/11/2002

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males or females
2. Aged 70-82 years
3. As diagnosed by the primary care physician, evidence of vascular disease including stable angina or intermittent claudication or stroke, transient ischaemic attack (TIA), myocardial infarction (MI), arterial surgery, or amputation for vascular disease more than 6 months prior to study entry
4. No evidence of previous vascular disease as stated above, but considered to be at high risk for vascular disease on the basis of:
4.1. Current smoking status
4.2. Hypertension, currently receiving drug treatment
4.3. Known diabetes mellitus
4.4. Total cholesterol 4.0 - 9.0 mmol/L

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

5500

Participant exclusion criteria

1. Recent stroke, TIA, MI, arterial surgery, or amputation for vascular disease less than 6 months prior to study entry
2. Any surgery requiring overnight hospitalisation (including angioplasty) less than 6 months prior to study entry
3. Poor cognitive function at baseline (Mini Mental Status Examination Score [MMSE] < 24)
4. Physically or mentally unable to attend the clinic for the screening visit
5. Cholesterol: Total cholesterol (TC < 4.0 mmol/L or TC > 9.0 mmol/L), Triglycerides (TG > 6.0 mmol/L)
6. Severe renal impairment (serum creatinine > 200 µmol/L)
7. Significant liver disease (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 X upper limit of normal for the laboratory)
8. History of malignancy within the past 5 years except localised basal cell carcinoma of the skin
9. Congestive heart failure (New York Heart Association Functional Class III or IV)
10. ECG evidence of atrial fibrillation, atrial flutter, or other significant arrhythmia, or Wolff-Parkinson-White Syndrome (WPW)
11. Significant untreated thyroid disease
12. Organ transplant recipient
13. Current lipid-lowering treatment
14. Previous participation in a clinical trial using an HMG CoA reductase inhibitor
15. Inability to give informed consent
16. Planned long-term travel or emigration within next 3 years
17. Current alcohol or drug abuse
18. Co-habitation with another trial participant
19. Less than 75% or greater than 120% compliance with placebo lead-in medication
20. Receipt of any investigational drugs (including placebo) within 30 days of enrolment
21. Inability to tolerate oral medication or a history of significant malabsorption
22. Any other medical condition which renders the patient unable to complete the study which would interfere with optimal participation in the study or produce significant risk to the patient

Abnormal laboratory findings include:
1. Hemoglobin < 11 g/dl
2. Hematocrit < 33%
3. Platelet count < 100,000/mm³
4. White blood cell count < 3,500/mm³ or > 15,000/mm³
5. Serum creatinine > 200 µmol/L
6. Potassium < 3.0 mmol/L or 5.0 mmol/L
7. Sodium < 130 mmol/L or 150 > mmol/L
8. Aspartate aminotransferase/alanine aminotransferase (AST or ALT) > 3.0 X upper limit of normal for the laboratory
9. Creatine kinase (CK) > 3 times upper limit of normal for the laboratory

Recruitment start date

01/12/1997

Recruitment end date

30/11/2002

Locations

Countries of recruitment

Ireland, Netherlands, United Kingdom

Trial participating centre

Robertson Centre for Biostatistics
Glasgow
G12 8QQ
United Kingdom

Sponsor information

Organisation

Bristol-Myers Squibb Company (USA)

Sponsor details

Corporate Headquarters
345 Park Avenue
New York
10154
United States of America

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Bristol-Myers Squibb Company (BMS) (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 1997 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/10569329
2. 2002 results in: http://www.ncbi.nlm.nih.gov/pubmed/12097148
3. 2002 results in: http://www.ncbi.nlm.nih.gov/pubmed/12457784
4. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24023757

Publication citations

  1. Results

    Ford I, Blauw GJ, Murphy MB, Shepherd J, Cobbe SM, Bollen EL, Buckley BM, Jukema JW, Hyland M, Gaw A, Lagaay AM, Perry IJ, Macfarlane P, Norrie J, Meinders AE, Sweeney BJ, Packard CJ, Westendorp RG, Twomey C, Stott DJ, , A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics., Curr Control Trials Cardiovasc Med, 2002, 3, 1, 8, doi: 10.1186/1468-6708-3-8.

  2. Results

    Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG, , Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial., Lancet, 2002, 360, 9346, 1623-1630.

  3. Results

    Lloyd SM, Stott DJ, de Craen AJ, Kearney PM, Sattar N, Perry I, Packard CJ, Briggs A, Marchbank L, Comber H, Jukema JW, Westendorp RG, Trompet S, Buckley BM, Ford I, Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)., PLoS ONE, 2013, 8, 9, e72642, doi: 10.1371/journal.pone.0072642.

  4. Shepherd J, Blauw GJ, Murphy MB, Cobbe SM, Bollen EL, Buckley BM, Ford I, Jukema JW, Hyland M, Gaw A, Lagaay AM, Perry IJ, Macfarlane PW, Meinders AE, Sweeney BJ, Packard CJ, Westendorp RG, Twomey C, Stott DJ, The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk., Am. J. Cardiol., 1999, 84, 10, 1192-1197.

Additional files

Editorial Notes