Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine

NCT00124072 | Completed Phase 3 Results DMC

• 1 other identifier: CTSUSEARCH1
• Study Type: interventional
• Target: 12,064
• Locations: 1 country
• Sites: 1

Brief Summary

SEARCH is a randomised, double-blind, multi-centre United Kingdom (UK) trial of 12,064 patients with myocardial infarction (MI) prior to study entry which aims to demonstrate whether a more intensive cholesterol lowering regimen using 80 mg simvastatin daily produces a larger and worthwhile reduction in cardiovascular events compared with a standard 20 mg daily regimen and whether reducing blood homocysteine levels with a daily dose of folic acid 2 mg + vitamin B12 1 mg compared with matching placebo produces a worthwhile reduction in vascular disease.

Conditions

Cardiovascular Disease

Keywords

Myocardial infarction; Coronary heart disease; Cholesterol; Stroke

Outcome Measures

Primary Outcomes (1)

• Major Vascular Events (MVE)

  Major vascular events (MVE) defined as major coronary events (MCE \[non-fatal MI, coronary death or coronary revascularisation\]), non-fatal or fatal stroke, or peripheral revascularization (peripheral artery angioplasty or arterial surgery, including amputations), during the scheduled study treatment period.

  6.7 years median follow-up

Secondary Outcomes (5)

• MVEs Separately in Year 1 and in Later Years

  6.7 years median follow-up

• MVEs in Patients Subdivided Into 3 Groups by Baseline Low-density Lipoprotein (LDL)

  6.7 years median follow-up

• MVEs in Presence and Absence of the Other Factorial Treatment

  6.7 years median follow-up

• Major Coronary Events

  6.7 years median follow-up

• Total Strokes

  6.7 years median follow-up

Study Arms (4)

Simvastatin 20 mg + folic acid and B12

ACTIVE COMPARATOR

Participants received 20 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily

Drug: Simvastatin 20 mg daily; Dietary Supplement: Folic acid 2 mg + vitamin B12 1 mg daily

Simvastatin 80 mg + folic acid and B12

ACTIVE COMPARATOR

Participants received 80 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily

Dietary Supplement: Folic acid 2 mg + vitamin B12 1 mg daily; Drug: Simvastatin 80 mg daily

Simvastatin 20 mg + placebo

ACTIVE COMPARATOR

Participants received 20 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily

Drug: Simvastatin 20 mg daily; Drug: Placebo

Simvastatin 80 mg + placebo

ACTIVE COMPARATOR

Participants received 80 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily

Drug: Simvastatin 80 mg daily; Drug: Placebo

Interventions

Simvastatin 20 mg daily DRUG

Simvastatin 20 mg tablet once daily

Simvastatin 20 mg + folic acid and B12; Simvastatin 20 mg + placebo

Folic acid 2 mg + vitamin B12 1 mg daily DIETARY_SUPPLEMENT

Folic acid 2 mg + vitamin B12 1 mg tablet once daily

Simvastatin 20 mg + folic acid and B12; Simvastatin 80 mg + folic acid and B12

Simvastatin 80 mg daily DRUG

Simvastatin 80 mg tablet once daily

Simvastatin 80 mg + folic acid and B12; Simvastatin 80 mg + placebo

Placebo DRUG

Placebo vitamin B12/folic acid tablet once daily

Simvastatin 20 mg + placebo; Simvastatin 80 mg + placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior myocardial infarction
• Statin therapy indicated
• No clear indication for folic acid

You may not qualify if:

• No clear contraindication to study treatments
• Screening plasma total cholesterol \<3.5 mmol/l in patient already on statin therapy, or \<4.5 mmol/l in patient not on statin therapy
• Chronic liver disease
• Severe renal disease or evidence of renal impairment
• Inflammatory muscle disease
• Concurrent treatment with fibrates or high-dose niacin
• Concurrent treatment with cyclosporin (or condition likely to result in organ transplantation and the need for cyclosporin), nefazodone, methotrexate, systemic azole antifungal or systemic macrolide antibiotics
• Child bearing potential
• No other predominant medical problem (other than coronary heart disease \[CHD\]) which might limit compliance with 5 years of study treatment

Sponsors & Collaborators

• University of Oxford: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

CTSU, Richard Doll Building, University of Oxford

Oxford, Oxon, OX3 7LF, United Kingdom

Location

Related Links

• SEARCH study website (primarily for dissemination of the results)

MeSH Terms

Conditions

Cardiovascular Diseases; Myocardial Infarction; Coronary Disease; Stroke

Interventions

Simvastatin; Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds

Results Point of Contact

• Title: CTSU Reception
• Organization: CTSU, University of Oxford

secretary@ctsu.ox.ac.uk

01865 743743

Study Officials

• Rory Collins, MB BS FRCP

  University of Oxford

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 22, 2005
• First Posted: July 26, 2005
• Study Start: July 1, 1998
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: February 1, 2012
• Results First Posted: June 9, 2010

Record last verified: 2012-01

Locations

GB (1)