Condition category
Circulatory System
Date applied
05/09/2005
Date assigned
05/09/2005
Last edited
03/08/2009
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://www.phri.ca

Contact information

Type

Scientific

Primary contact

Dr Eva Lonn

ORCID ID

Contact details

HGH-McMaster Clinic
237 Barton Street East
Room 254
Hamilton
L8L 2X2
Canada
+1 905 526 0970
lonnem@mcmaster.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00106886

Protocol/serial number

MCT-15428

Study information

Scientific title

Acronym

HOPE-2

Study hypothesis

1. To evaluate whether prolonged therapy with folic acid and vitamins B6 and B12 compared to placebo reduces the risk of cardiovascular death, myocardial infarction (MI) and stroke (major fatal and non-fatal cardiovascular [CV] events)
2. To evaluate the effects of the study intervention on major fatal and non-fatal CV and revascularisation procedures and on total important ischaemic events

Ethics approval

Hamilton Health Sciences Corporation and McMaster University approved on the 17th November 1999.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Cardiovascular disease, myocardial infarction (MI), stroke, cancer

Intervention

Combination pill containing: Folic acid 2.5 mg, vitamin B6 50 mg, vitamin B12 1 mg, or placebo

Intervention type

Supplement

Phase

Not Applicable

Drug names

Folic acid, vitamins B6 and B12

Primary outcome measures

The composite of cardiovascular death, myocardial infarction (MI) and stroke.

Secondary outcome measures

1. Total major ischaemic events, including CV death, MI, stroke, hospitalisations for unstable angina and revascularisations
2. Total mortality
3. Hospitalisation for unstable angina (UA)
4. Hospitalisation for congestive heart failure (CHF)
5. Revascularisation procedures
6. Incident cancer
7. Cancer death

Overall trial start date

01/04/1999

Overall trial end date

31/03/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women and men 55 years of age or over with established CVD and at high risk for future fatal and nonfatal CV events defined as:
1.1. Documented coronary artery disease (CAD)
1.2. Documented peripheral vascular disease (PVD)
1.3. Documented cerebrovascular disease
1.4. Diabetes with one of the following additional cardiovascular risk factors:
1.4.1. Hypertension (blood pressure [BP] greater than 160 mmHg systolic or greater than 90 mmHg diastolic or on treatment)
1.4.2. Total cholesterol greater than 5.2 mmol/l (greater than 200 mg/dl)
1.4.3. High density lipoprotein (HDL) cholesterol less than 0.9 mmol/l (3.5 mg/dl)
1.4.4. Current cigarette smoker
1.4.5. Any evidence of previous vascular disease
2. Provision of informed consent

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

5552

Participant exclusion criteria

1. Current use of any vitamin supplements containing folic acid greater than 200 µg/day. Patients taking such vitamin supplements can be asked if they agree to discontinue these supplements. If they agree they can be randomised to the study.
2. Known previous adverse reactions to folic acid, vitamin B6 or B12
3. Planned cardiac, peripheral or cerebrovascular revascularization, defined as a decision taken by the patient and his or her physician(s) to perform surgical or percutaneous transluminal revascularisation within the next 6 months
4. Haemodynamically significant primary valvular outflow tract obstruction (e.g. mitral stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve)
5. Constrictive pericarditis
6. Complex congenital heart disease
7. Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias (asymptomatic arrhythmias including ventricular tachycardia are not exclusion criteria)
8. Uncontrolled hypertension
9. Cor pulmonale
10. Heart transplant recipient
11. Other important non-cardiovascular disease(s) expected to limit compliance and/or impact on patient’s ability to complete the study, such as: history of alcohol or drug abuse, psychiatric disorders, senility, severe physical disability, illnesses including terminal stage cancer and other major systemic illnesses expected to limit the patient’s ability to comply with the study protocol and to complete the study

Recruitment start date

01/04/1999

Recruitment end date

31/03/2006

Locations

Countries of recruitment

Canada

Trial participating centre

HGH-McMaster Clinic
Hamilton
L8L 2X2
Canada

Sponsor information

Organisation

McMaster University (Canada)

Sponsor details

Office of the Associate Dean
Research
McMaster University
Faculty of Health Sciences
1200 Main Street West
Room HSC-3N8
Hamilton
L8N 3Z5
Canada

Sponsor type

University/education

Website

http://www.mcmaster.ca/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-15428)

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. 2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16531613
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17470822
3. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19228852

Publication citations

  1. Results

    Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J, , Homocysteine lowering with folic acid and B vitamins in vascular disease., N. Engl. J. Med., 2006, 354, 15, 1567-1577, doi: 10.1056/NEJMoa060900.

  2. Results

    Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E, , Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial., Ann. Intern. Med., 2007, 146, 11, 761-767.

  3. Results

    Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E, , Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial., Stroke, 2009, 40, 4, 1365-1372, doi: 10.1161/STROKEAHA.108.529503.

Additional files

Editorial Notes