Scarpini E, Bruno G, Zappala G, et al. Cessation versus Continuation of Galantamine Treatment after 12 Months of Therapy in Patients with Alzheimer’s Disease: A Randomized, Double Blind, Placebo Controlled Withdrawal Trial. Journal of Alzheimers Disease 2011;26:211-20.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/21606568
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 139 randomized, 55 completed
· Active deprescribing group: 63 randomized, 19 completed · Control group: 76 randomized, 36 completed Age: 74.5 years Sex: 83 female, 56 male Participants with dementia: all with mild to moderate cognitive impairment – MMSE score from 11 to 24 Inclusion criteria: · Outpatients · Aged ≥50 years · Diagnosis of probable Alzheimer’s Disease according to the National Institute of Neurologic and Communicative Disorders and Stroke Alzheimer’s Disease and Related Disorders Association · Mild to moderate cognitive impairment – MMSE score from 11 to 24 Exclusion criteria: · Presence of a neurodegenerative disorder other than Alzheimer’s Disease · Any serious and clinically significant illness · History of previous cerebral infarction · Use of acetylcholinesterase inhibitors within 3 months before inclusion · Subjects had to be withdrawn from the study if they: o Showed a cognitive deterioration (≥4 points of the Alzheimer’s Disease Assessment Scale-cognitive sub-scale at the end of the open-label phase or during the double-blind phase o They or their caregiver withdrew consent o Randomization code was broken o Serious adverse event occurred o Investigator considered it to be in the best interest of the patient Concomitant medicines: Antidepressants, mood stabilizers, and cholinomimetics were not allowed during the trial. Anti-dementia agents other than study drug were not allowed during the trial: cholinesterase inhibitors (donepezil, tacrine, rivastigmine), nootropics Country: Italy Setting: Community – 29 clinics across Italy with randomization balanced between the centers |
| Interventions | Medicine: Galantamine
Withdrawal schedule: Not described Comparator: Placebo compared to continued treatment |
| Outcomes | Drop-outs
Adverse drug events |
| Dates | Dates: July 2001 (first subject in) and November 2005 (last subject out).
Follow-up duration: 36 months total: 12 months drug treatment and 24 months of deprescribing |
| Funding sources | “Sara Hughes and Nancy Milligan of Dianthus Medical Limited for assistance in preparing the manuscript on behalf of Janssen-Cilag GmbH in accordance with the European Medical Writers Association guidelines.
Adam Jacobs undertook the statistical analyses and supported the development and finalization of the manuscript. Janssen-Cilag EMEA provided funding for this manuscript and was involved in the design and |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Low risk | “At the beginning of the open-label phase, subjects were given a subject number corresponding to a computer-generated randomization code. Subjects were randomly allocated to treatment 1: 1.”
“The randomization code was generated by Janssen Pharmaceutica, Beerse, Belgium. Randomization was balanced between the centers. Each study |
| Allocation concealment (selection bias) | Low risk | Was done before an open-label phase.
“…assigned subject numbers consecutively starting with the lowest available number.” |
| Blinding of participants and personnel (performance bias) | Low risk | “For the double-blind phase, centers received boxes containing 27 blisters of 14 tablets each. It was not possible to distinguish boxes containing active drug from those containing placebo. Galantamine and placebo tablets were identical in appearance, taste, and smell.” |
| Blinding of outcome assessment (detection bias) | Unclear risk | Not stated |
| Incomplete outcome data (attrition bias) | Low risk | Intention-to-treat analysis for both open and blinded phases |
| Selective reporting (reporting bias) | Low risk | Stated outcomes were all reportedthough an a priori published protocol was not found. |
| Other bias | High risk | Industry-sponsored trial. This was sponsored by Janssen, maker of the drug being studied. |
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