Grossberg 2020b.
| Study characteristics | ||
| Methods |
Study design: randomised controlled trial Group: parallel group Study duration: 12 weeks Rescue medication: allowed: antidepressants (if the dose was stable for 30 days prior to randomisation and did not change during the study) and benzodiazepines (during the first 4 weeks of the randomized phase only (limited to 4 days/week with a maximum dose of 2 mg/day of lorazepam or equivalent) |
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| Participants |
Number randomised: 270 (133 brexpiprazole, 137 placebo) Mean age: 73.8 years Sex (female): 63.0% Type of dementia: Alzheimer's disease Severity of dementia: mild‐severe Indication: agitation (baseline CMAI 69.9) Setting: care facility or community‐dwelling, provided the patient was not living alone Country: Ukraine (28.9% of randomised patients), the USA (22.6%), Russia (19.3%), Bulgaria (17.8%), Canada (4.8%), France (3.3%), Slovenia (2.2%), the UK (0.7%), and Finland (0.4%) |
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| Interventions | Brexpiprazole: flexible dose 0.5 m to 2mg/day, mean dose 1.54 mg/day. Placebo Brexpiprazole was initiated at 0.25 mg/day (days 1−3), increased to 0.5 mg/day (days 4−14), and further increased to a target dose of 1 mg/day (days 15−28; could be decreased back to 0.5 mg/day). An additional dose increase to 2 mg/day could be initiated from day 29 (week 4 visit) onwards. After week 4, stepwise dose decreases and increases could occur at any time (scheduled or unscheduled visits), based on the investigator’s clinical evaluation of the patient’s response and tolerability. Patients unable to tolerate brexpiprazole 0.5 mg/day (or matching placebo) were discontinued from the trial. |
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| Outcomes | Agitation: Cohen‐Mansfield Agitation Inventory (CMAI) Extrapyramidal symptoms Somnolence Death Any adverse event Any serious adverse event Discontinuation (any reason) Discontinuation due to adverse events Cognitive function: Mini‐Mental State Examination (MMSE) |
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| Identification | ||
| Notes | Sponsorship Source: Otsuka Pharmaceutical Development & Commercialization Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Treatments were assigned by an interactive voice/web response system based on a fixed‐block, computer‐generated randomization code provided by the study sponsor and stratified by study center." |
| Allocation concealment (selection bias) | Unclear risk | No information provided |
| Comparability of groups (selection bias) | Unclear risk | There are several small differences that were not taken into account, and might have influence the results |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Treatment assignments were blinded to patients, investigators, and sponsor personnel..." "Brexpiprazole and matching placebo tablets were provided by the sponsor, packaged in numbered, weekly blister cards." |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Treatment assignments were blinded to patients, investigators, and sponsor personnel..." |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Overall and differential drop‐out low. ITT not used, but given negative study results this was probably not problematic |
| Selective reporting (reporting bias) | High risk | Many outcomes mentioned on clinicaltrials.gov have not been reported |
| Other bias | High risk | 6‐week run‐in for wash‐out |