Trial Outcomes & Findings for Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (NCT NCT00124072)
NCT ID: NCT00124072
Last Updated: 2012-02-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
12064 participants
Primary outcome timeframe
6.7 years median follow-up
Results posted on
2012-02-01
Participant Flow
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.
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.
Participant milestones
| Measure |
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
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3017
|
3016
|
3016
|
3015
|
|
Overall Study
COMPLETED
|
2503
|
2504
|
2524
|
2515
|
|
Overall Study
NOT COMPLETED
|
514
|
512
|
492
|
500
|
Reasons for withdrawal
| Measure |
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
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up for Mortality
|
0
|
3
|
2
|
2
|
|
Overall Study
Lost to Follow-up for Morbidity
|
15
|
25
|
19
|
18
|
|
Overall Study
Death
|
499
|
484
|
471
|
480
|
Baseline Characteristics
Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine
Baseline characteristics by cohort
| Measure |
Simvastatin 20 mg + Folic Acid and B12
n=3017 Participants
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
n=3016 Participants
Participants received 80 mg simvastatin once daily, and 2 mg folic acid with 1 mg vitamin B12 once daily
|
Simvastatin 20 mg + Placebo
n=3016 Participants
Participants received 20 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily
|
Simvastatin 80 mg + Placebo
n=3015 Participants
Participants received 80 mg simvastatin once daily, and placebo folic acid with placebo vitamin B12 once daily
|
Total
n=12064 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
64.2 years
STANDARD_DEVIATION 8.9 • n=99 Participants
|
64.2 years
STANDARD_DEVIATION 8.9 • n=107 Participants
|
64.2 years
STANDARD_DEVIATION 8.9 • n=206 Participants
|
64.2 years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
64.2 years
STANDARD_DEVIATION 8.9 • n=31 Participants
|
|
Sex: Female, Male
Female
|
513 Participants
n=99 Participants
|
514 Participants
n=107 Participants
|
513 Participants
n=206 Participants
|
512 Participants
n=7 Participants
|
2052 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
2504 Participants
n=99 Participants
|
2502 Participants
n=107 Participants
|
2503 Participants
n=206 Participants
|
2503 Participants
n=7 Participants
|
10012 Participants
n=31 Participants
|
|
Region of Enrollment
United Kingdom
|
3017 participants
n=99 Participants
|
3016 participants
n=107 Participants
|
3016 participants
n=206 Participants
|
3015 participants
n=7 Participants
|
12064 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 6.7 years median follow-upMajor 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.
Outcome measures
| Measure |
Simvastatin 20 mg Daily
n=6033 Participants
Simvastatin 20 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 20 mg daily + placebo vitamin B12/folic acid
|
Simvastatin 80 mg Daily
n=6031 Participants
Simvastatin 80 mg tablet once daily in the following arms: simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
Folic Acid 2 mg + Vitamin B12 1 mg Daily
n=6033 Participants
Folic acid 2 mg + vitamin B12 1 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active)
|
Placebo
n=6031 Participants
Placebo vitamin B12/folic acid tablet once daily in the following arms: simvastatin 20 mg daily + placebo vitamin B12/folic acid; simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
|---|---|---|---|---|
|
Major Vascular Events (MVE)
|
1553 Participants
|
1477 Participants
|
1537 Participants
|
1493 Participants
|
SECONDARY outcome
Timeframe: 6.7 years median follow-upOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6.7 years median follow-upOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6.7 years median follow-upOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6.7 years median follow-upNon-fatal MI, coronary death or coronary revascularisation
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6.7 years median follow-upOutcome measures
Outcome data not reported
Adverse Events
Simvastatin 20 mg Daily
Serious events: 5037 serious events
Other events: 479 other events
Deaths: 0 deaths
Simvastatin 80 mg Daily
Serious events: 5024 serious events
Other events: 493 other events
Deaths: 0 deaths
Folic Acid 2 mg + Vitamin B12 1 mg Daily
Serious events: 5068 serious events
Other events: 480 other events
Deaths: 0 deaths
Placebo
Serious events: 4993 serious events
Other events: 492 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Simvastatin 20 mg Daily
n=6033 participants at risk
Simvastatin 20 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 20 mg daily + placebo vitamin B12/folic acid
|
Simvastatin 80 mg Daily
n=6031 participants at risk
Simvastatin 80 mg tablet once daily in the following arms: simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
Folic Acid 2 mg + Vitamin B12 1 mg Daily
n=6033 participants at risk
Folic acid 2 mg + vitamin B12 1 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active)
|
Placebo
n=6031 participants at risk
Placebo vitamin B12/folic acid tablet once daily in the following arms: simvastatin 20 mg daily + placebo vitamin B12/folic acid; simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
|---|---|---|---|---|
|
Vascular disorders
MVE
|
25.7%
1553/6033 • 6.7 years median follow-up
|
24.5%
1477/6031 • 6.7 years median follow-up
|
25.5%
1537/6033 • 6.7 years median follow-up
|
24.8%
1493/6031 • 6.7 years median follow-up
|
|
General disorders
Other
|
57.7%
3484/6033 • 6.7 years median follow-up
|
58.8%
3547/6031 • 6.7 years median follow-up
|
58.5%
3531/6033 • 6.7 years median follow-up
|
58.0%
3500/6031 • 6.7 years median follow-up
|
Other adverse events
| Measure |
Simvastatin 20 mg Daily
n=6033 participants at risk
Simvastatin 20 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 20 mg daily + placebo vitamin B12/folic acid
|
Simvastatin 80 mg Daily
n=6031 participants at risk
Simvastatin 80 mg tablet once daily in the following arms: simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
Folic Acid 2 mg + Vitamin B12 1 mg Daily
n=6033 participants at risk
Folic acid 2 mg + vitamin B12 1 mg tablet once daily in the following arms: simvastatin 20 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active); simvastatin 80 mg daily + folic acid 2 mg and vitamin B12 1 mg daily (active)
|
Placebo
n=6031 participants at risk
Placebo vitamin B12/folic acid tablet once daily in the following arms: simvastatin 20 mg daily + placebo vitamin B12/folic acid; simvastatin 80 mg daily + placebo vitamin B12/folic acid
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain or indigestion
|
2.4%
143/6033 • 6.7 years median follow-up
|
2.8%
167/6031 • 6.7 years median follow-up
|
2.6%
156/6033 • 6.7 years median follow-up
|
2.6%
154/6031 • 6.7 years median follow-up
|
|
General disorders
Tiredness or lethargy
|
2.7%
165/6033 • 6.7 years median follow-up
|
2.5%
152/6031 • 6.7 years median follow-up
|
2.7%
162/6033 • 6.7 years median follow-up
|
2.6%
155/6031 • 6.7 years median follow-up
|
|
General disorders
Other and unspecified symptom or problem
|
2.8%
171/6033 • 6.7 years median follow-up
|
2.9%
174/6031 • 6.7 years median follow-up
|
2.7%
162/6033 • 6.7 years median follow-up
|
3.0%
183/6031 • 6.7 years median follow-up
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place