Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial

ISRCTN	ISRCTN14780645
DOI	https://doi.org/10.1186/ISRCTN14780645
ClinicalTrials.gov number	NCT00468923
Secondary identifying numbers	IR2-91038

Submission date: 07/10/2008
Registration date: 12/11/2008
Last edited: 25/03/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Salim Yusuf
Scientific

Population Health Research Institute
McMaster Clinic
237 Barton Street East
Hamilton, Ontario
L8L 2X2
Canada

Phone	+1 905 527 7327
Email	hope3@phri.ca

Study information

Study design	Interventional randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	HOPE-3
Study objectives	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(s)	Research Ethics Board of McMaster University gave approval on the 16th April 2007 (ref: 06-434)
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Rosuvastatin, candesartan/hydrochlorothiazide
Primary outcome measure	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 study start date	01/05/2007
Completion date	31/05/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	11000
Key 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
Key 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
Date of first enrolment	01/05/2007
Date of final enrolment	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

Study participating centre

Population Health Research Institute

Hamilton, Ontario
L8L 2X2
Canada

Sponsor information

Hamilton Health Sciences Corporation (Canada)
Research organisation

237 Barton Street East
Hamilton, Ontario
L8L 2X2
Canada

Website	http://www.hamiltonhealthsciences.ca/
"ROR"	https://ror.org/02dqdxm48

Funders

Funder type

Research organisation

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

No information available

AstraZeneca (Canada)
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Results article	results	01/03/2016	Yes	No
Results article	results	26/05/2016	Yes	No
Results article	results	26/05/2016	Yes	No
Results article	results	26/05/2016	Yes	No
Results article	results	26/03/2019	Yes	No

Editorial Notes

25/03/2019: Publication reference added.