Feldman 2007
| Methods | 48‐month, double‐blind, parallel‐group, placebo‐controlled, randomised clinical trial with 3 phases (the first being the double‐blind component) | |
| Participants | 14 countries 65 centres 1526 individuals screened 1018 individuals enrolled, aged 55 to 85 years Selection criteria: cognitive symptoms, CDR = 0.5, NYU paragraph recall < 9, modified Hachinski ≤ 4 Exclusion criteria: AD according to DSM‐IV‐TR or NINCDS‐ADRDA criteria, HAM‐D ≥13, any primary neurodegenerative disease, any advanced, severe unstable medical condition, uncontrolled seizure disorder, any history of TIA, any severe or unstable cardiovascular disease or asthma, known hypersensitivity to cholinesterase inhibitors, received cholinergic drug in the past 2 weeks, rivastigmine in the previous 4 weeks, or had previously taken part in a rivastigmine trial |
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| Interventions | 1. Rivastigmine 0.5 mg bd increased to 1.5 mg bd after 2 weeks and subsequently increasing by a further 1.5 mg bd at a minimum of 4‐weekly intervals to a maximum of 12 mg daily (minimum 3 mg daily) 2. Placebo |
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| Outcomes | Time to clinical diagnosis of AD Difference between groups in change from baseline in a 10‐test neuropsychological test battery: (NYU paragraph recall, delayed word list recall, letter number sequencing, Buschke selective reminding task, symbol‐digit modalities task, digit cancellation task, maze, verbal fluencies categories subtest, and clock drawing) ADAS‐Cog MMSE ADCS‐ADL BDI NPI Quality of life |
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| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "The randomisation procedure used a validated interactive voice‐response system with an automated assignment of treatment groups" |
| Allocation concealment (selection bias) | Low risk | Quote: "The randomisation procedure used a validated interactive voice‐response system with an automated assignment of treatment groups" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Quote: "To preserve the blinding, the rivastigmine and placebo capsules were identical in shape, size, and colour. Study drugs were dispensed in bottles labelled with unique numbers. All personnel directly involved in the study were blind to the treatment group allocation until all patients had completed the trial and all data had been finalised for analysis" |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | A large number of drop‐outs were later recovered for later stages of the study after the double‐blind portion of the trial was complete |
| Selective reporting (reporting bias) | Low risk | All outcomes reported |
| Other bias | Low risk | No additional biases |