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Table 1 Protocol amendments and other changes to trial practice

From: Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

Criterion

Previous versions

Current version/status

Reason

Protocol changes

   

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

< 4.0 mmol

< 3.1 mmol/l

Ditto

Glucose monitoring

 

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

2 weeks

1 week

To accelerate recruitment

Guideline statin dosage

Simvastatin 40 mg, pravastatin 40 mg, fluvastatin 40 mg

Simvastatin 10 to 40 mg, pravastatin 10 to 40 mg, fluvastatin 10 to 80 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

8 years

4 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

 

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 6 months

To assess latest BP and/or lipid levels and escalate treatment as appropriate

Other changes

   

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

 

Twice yearly to investigators.

To highlight the need to achieve targets in BP and lipid lowering in patients randomised to intensive management