Condition category
Circulatory System
Date applied
07/10/2008
Date assigned
12/11/2008
Last edited
16/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://rome.cardio.on.ca/hope3

Contact information

Type

Scientific

Primary contact

Dr Salim Yusuf

ORCID ID

Contact details

Population Health Research Institute
McMaster Clinic
237 Barton Street East
Hamilton
Ontario
L8L 2X2
Canada
+1 905 527 7327
hope3@phri.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00468923

Protocol/serial number

IR2-91038

Study information

Scientific title

Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial: a large simple randomised trial of combined cholesterol modification and blood pressure lowering in middle aged people at average risk

Acronym

HOPE-3

Study hypothesis

In individuals at moderate risk and without known atherothrombotic cardiovascular disease (CVD):
1. To evaluate the effects of lipid modification (low density lipoprotein [LDL] cholesterol lowering and high density lipoprotein [HDL] cholesterol raising) with rosuvastatin 10 mg daily on major cardiovascular (CV) events
2. To evaluate the effects of blood pressure lowering with combined candesartan 16 mg/hydrochlorothiazide (HCT) 12.5 mg daily on major CV events
3. To evaluate the impact of combined lipid modification with rosuvastatin 10 mg/day and blood pressure lowering with candesartan 16 mg/HCT 12.5 mg daily on major CV events

Ethics approval

Research Ethics Board of McMaster University gave approval on the 16th April 2007 (ref: 06-434)

Study design

Interventional randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Cardiovascular disease/stroke

Intervention

Experimental group:
Rosuvastatin 10 mg, once a day
Candesartan 16 mg/hydrochlorothiazide (HCT) 12.5 mg, once a day

Control group:
Matching placebo 10 mg, once a day
Matching placebo 16 mg/HCT 12.5 mg, once a day

An average of at least 5 years of follow-up for both study arms.

Contact for public queries:
HOPE-3 Project Office
237 Barton St. E.
Hamilton, Ontario
L8L 2X2
Canada
Tel: +1 905 527 4322 ext. 44529
Fax: +1 905 527 5380
Email: hope3@phri.ca

Intervention type

Drug

Phase

Not Specified

Drug names

Rosuvastatin, candesartan/hydrochlorothiazide

Primary outcome measures

The composite of CV death, non-fatal myocardial infarction (MI) and non-fatal stroke, measured at 6 weeks, 6 months and then every 6 months until study end.

Secondary outcome measures

1. The composite of CV death, non-fatal MI, non-fatal stroke, resuscitated cardiac arrest, coronary revascularisation with objective evidence of ischaemia and heart failure measured at 6 weeks, 6 months, and then every 6 months until study end
2. Total mortality measured at 6 weeks, 6 months, and then every 6 months until study end

Overall trial start date

01/05/2007

Overall trial end date

31/05/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women aged greater than or equal to 60 years with at least two additional risk factors and, women aged greater than or equal to 65 years and men greater than or equal to 55 years with at least one additional risk factor
2. Suggested CV risk factors for trial eligibility:
2.1. Waist/hip ratio greater than 0.90 in men and greater than 0.85 in women
2.2. History of current or recent smoking (regular tobacco use within 5 years)
2.3. Low HDL cholesterol (for example, HDL cholesterol less than 1.0 mmol/L [40 mg/dl] in men and less than 1.3 mmol/L [50 mg/dl] in women)
2.4. Dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or uncomplicated diabetes treated by diet only)
2.5. Renal dysfunction:
2.5.1. Microalbuminuria
2.5.2. Estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m^2 or serum creatinine greater than 124 µmol/L (1.4 mg/dL) (unless participant has proteinuria or blood pressure above 130/80 mmHg)
2.6. Family history of premature coronary heart disease (CHD) in first degree relatives (age less than 55 years in men or less than 65 years in women)
3. Provision of informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

11000

Participant exclusion criteria

1. Documented clinically manifest atherothrombotic CVD
2. Clear indication for statin and/or angiotensin-receptor blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor and/or thiazide diuretic therapy, as determined by the subject's own local physician
3. Clear contraindication for statin and/or ARB or ACE inhibitor and/or thiazide diuretic therapy, as determined by the subject's own local physician
4. Symptomatic hypotension
5. Chronic liver disease (i.e. cirrhosis or persistent hepatitis) or abnormal liver function, i.e. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 x upper limit of normal (ULN)
6. Inflammatory muscle disease (such as dermatomyositis or polymyositis) or creatine kinase (CK) greater than 3 x ULN
7. Moderate renal dysfunction (serum creatinine greater than 180 µmol/L [2.0 mg/dl] or eGFR less than 45 ml/min/1.73 m^2)
8. Mild renal dysfunction (eGFR less than 60 ml/min/1.73 m^2) and proteinuria or blood pressure above 130/80 mmHg
9. Concurrent treatment with cyclosporin or a condition likely to result in organ transplantation and the need for cyclosporin
10. Concurrent treatment with a statin or a fibrate (subjects on cholesterol-lowering diets or drugs other than statins or fibrates can still be included)
11. Concurrent treatment with an angiotensin receptor blocker, ACE inhibitor, or a thiazide diuretic
12. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial
13. Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the trial procedures
14. Concurrent use of an experimental pharmacological agent

Recruitment start date

01/05/2007

Recruitment end date

31/05/2013

Locations

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Czech Republic, Hungary, India, Korea, South, Malaysia, Netherlands, Philippines, Russian Federation, Slovakia, South Africa, Sweden, Ukraine

Trial participating centre

Population Health Research Institute
Hamilton, Ontario
L8L 2X2
Canada

Sponsor information

Organisation

Hamilton Health Sciences Corporation (Canada)

Sponsor details

237 Barton Street East
Hamilton
Ontario
L8L 2X2
Canada

Sponsor type

Research organisation

Website

http://www.hamiltonhealthsciences.ca/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: IR2-91038)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

AstraZeneca (Canada)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

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

Publication citations

Additional files

Editorial Notes