Criterion | Previous versions | Current version/status | Reason |
---|---|---|---|
Protocol changes | Â | Â | Â |
Posterior circulation stroke (POCS) | Excluded | Included | To expand the inclusion criteria; posterior circulation stroke can lead to cognitive decline |
Exclusion of NYHA 3 or 4 | Exclusion criterion | Removed | To simplify protocol |
LDL-c target | < 2.0 mmol/l | < 1.4 mmol/l | Half of patients already at LDL-c < 2 at baseline |
Total cholesterol | < 4.0Â mmol | < 3.1Â mmol/l | Ditto |
Glucose monitoring | Â | Glucose, HbA1C | Some BP and lipid drugs may reduce, or cause, diabetes mellitus |
Quality of life | DEMQOL | Removed | To simplify protocol |
Screening | As telephone call | As research clinic visit | To reduce recruitment of ineligible patients |
Time from screening to randomisation | 2Â weeks | 1Â week | To accelerate recruitment |
Guideline statin dosage | Simvastatin 40Â mg, pravastatin 40Â mg, fluvastatin 40Â mg | Simvastatin 10 to 40Â mg, pravastatin 10 to 40Â mg, fluvastatin 10 to 80Â mg | To reflect NICE guidelines on lipid management (CG 67, 2008) |
Statin classification | Guideline statin: | Guideline statin: | To clarify intensive versus guideline lipid lowering management |
simvastatin < 40 mg, pravastatin any dose, fluvastatin any dose, atorvastatin 10 mg. | simvastatin ≤ 40 mg, pravastatin any dose, fluvastatin any dose, atorvastatin ≤ 20 mg. | ||
Intensive statin: atorvastatin ≤ 40 mg | Intensive statin: atorvastatin > 20 mg, rosuvastatin any dose | ||
Trial duration and participant involvement | 8Â years | 4Â years | To shorten trial since the main phase is no longer justified |
BP and lipid management in follow-up visits |  | ‘Floating’ visit at any time outside the planned visits at 3, 6, 12, 18, 24, 30, 36 and 42 months | To allow enhanced escalation of treatment, as appropriate |
Baseline and follow-up BP and HR monitoring | Three measurements in rapid succession | Four measurements in rapid succession including one standing | To detect postural hypotension |
Neuroimaging sub-study scan | Â | CT scan on treatment (plus collection of any clinical scans during treatment) | To detect potential affects on atrophy, white matter changes |
Follow-up visits | Seen in clinic once a year with interval blinded telephone follow-up. | Seen in clinic once every 6Â months | To assess latest BP and/or lipid levels and escalate treatment as appropriate |
Other changes | Â | Â | Â |
Minimisation variables | As in section Minimisation (on key prognostic/logistical variables) above | Age, systolic BP, LDL-c | Small trial size precluded numerous minimisation variables |
Email reminders | Â | Twice yearly to investigators. | To highlight the need to achieve targets in BP and lipid lowering in patients randomised to intensive management |