Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00124072
First received: July 22, 2005
Last updated: January 31, 2012
Last verified: January 2012
Results First Received: March 29, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Cardiovascular Disease
Interventions: Drug: Simvastatin 20 mg daily
Dietary Supplement: Folic acid 2 mg + vitamin B12 1 mg daily
Drug: Simvastatin 80 mg daily
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First Patient In: 28-SEP-1998, Last Patient Last Visit: 22-May-2008 Eighty-eight (88) sites in 3 countries: England 72, Scotland 12 and Wales 4.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients entered a run-in period during which they received simvastatin 20 mg daily and placebo-vitamin tablets for 2 months. Eligible patients who completed run-in were then randomized in a 2x2 factorial blinded design between simvastatin 80 mg daily versus simvastatin 20 mg daily and folic acid 2 mg + vitamin B12 1 mg daily versus placebo.

Reporting Groups
  Description
Simvastatin 20 mg + Folic Acid and B12 Participants received 20 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily
Simvastatin 80 mg + Folic Acid and B12 Participants received 80 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily
Simvastatin 20 mg + Placebo Participants received 20 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily
Simvastatin 80 mg + Placebo Participants received 80 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily

Participant Flow:   Overall Study
    Simvastatin 20 mg + Folic Acid and B12     Simvastatin 80 mg + Folic Acid and B12     Simvastatin 20 mg + Placebo     Simvastatin 80 mg + Placebo  
STARTED     3017     3016     3016     3015  
COMPLETED     2503     2504     2524     2515  
NOT COMPLETED     514     512     492     500  
Lost to Follow-up for Mortality                 0                 3                 2                 2  
Lost to Follow-up for Morbidity                 15                 25                 19                 18  
Death                 499                 484                 471                 480  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Simvastatin 20 mg + Folic Acid and B12 Participants received 20 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily
Simvastatin 80 mg + Folic Acid and B12 Participants received 80 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily
Simvastatin 20 mg + Placebo Participants received 20 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily
Simvastatin 80 mg + Placebo Participants received 80 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily
Total Total of all reporting groups

Baseline Measures
    Simvastatin 20 mg + Folic Acid and B12     Simvastatin 80 mg + Folic Acid and B12     Simvastatin 20 mg + Placebo     Simvastatin 80 mg + Placebo     Total  
Number of Participants  
[units: participants]
  3017     3016     3016     3015     12064  
Age  
[units: years]
Mean ± Standard Deviation
  64.2  ± 8.9     64.2  ± 8.9     64.2  ± 8.9     64.2  ± 8.9     64.2  ± 8.9  
Gender  
[units: participants]
         
Female     513     514     513     512     2052  
Male     2504     2502     2503     2503     10012  
Region of Enrollment  
[units: participants]
         
United Kingdom     3017     3016     3016     3015     12064  



  Outcome Measures

1.  Primary:   Major Vascular Events (MVE)   [ Time Frame: 6.7 years median follow-up ]

2.  Secondary:   MVEs Separately in Year 1 and in Later Years   [ Time Frame: 6.7 years median follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   MVEs in Patients Subdivided Into 3 Groups by Baseline Low-density Lipoprotein (LDL)   [ Time Frame: 6.7 years median follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   MVEs in Presence and Absence of the Other Factorial Treatment   [ Time Frame: 6.7 years median follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Major Coronary Events   [ Time Frame: 6.7 years median follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Secondary:   Total Strokes   [ Time Frame: 6.7 years median follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: CTSU Reception
Organization: CTSU, University of Oxford
phone: 01865 743743
e-mail: secretary@ctsu.ox.ac.uk


No publications provided


Responsible Party: Professor Rory Collins, University of Oxford
ClinicalTrials.gov Identifier: NCT00124072     History of Changes
Other Study ID Numbers: CTSUSEARCH1
Study First Received: July 22, 2005
Results First Received: March 29, 2010
Last Updated: January 31, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency