Home › Research › Clinical trials
A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group
Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI.. JAMA, 1994-04-01
Topic: Drug trials: efficacy and safety
Objective To evaluate the efficacy and safety of high-dose tacrine hydrochloride over 30 weeks in patients with probable Alzheimer's disease. Design A 30-week randomized, double-blind, placebo-controlled, parallel-group trial. Setting Outpatients at 33 US centers. Patients Men and women at least 50 years of age with mild to moderate Alzheimer's disease and otherwise in good health. Interventions Group 1 received placebo; group 2 received 40 mg/d of tacrine for 6 weeks, then 80 mg/d for 24 weeks; groups 3 and 4 received 40 mg/d of tacrine for 6 weeks, 80 mg/d for 6 weeks, and 120 mg/d for 6 weeks. Group 3 remained on a dosage of 120 mg/d for a total of 18 weeks; after 6 weeks at 120 mg/d, group 4 titrated to 160 mg/d for the last 12 weeks. Primary outcome measures Clinician Interview-Based Impression (CIBI), Alzheimer's Disease Assessment Scale--Cognitive subscale (ADAS-Cog), and Final Comprehensive Consensus Assessment (FCCA). Results A total of 663 patients entered the study; 653 patients were included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30 weeks. The results of the ITT analysis revealed significant (P < or = .05) dose-response trends and between-group comparisons on CIBI and ADAS-Cog. In evaluable patients, significant dose-response trends were observed for all three primary measures (P < or = .001). Significant differences in favor of 160 mg/d of tacrine vs placebo were observed on the CIBI (P < or = .002) and ADAS-Cog and FCCA (P < or = .001), as well as caregiver-global and quality-of-life assessments (P < or = .05). On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and evaluable-patient populations, respectively, were rated improved compared with 17% and 18% of placebo patients, respectively. The primary reasons for withdrawal of tacrine-treated patients were asymptomatic liver transaminase elevations (28%) and gastrointestinal complaints (16%). These adverse events were reversible on discontinuation of treatment, and many patients were able to restart tacrine. Conclusions Tacrine produced statistically significant, dose-related improvements on objective performance-based tests, clinician- and caregiver-rated global evaluations, and measures of quality of life. There was no evidence that the large number of patient withdrawals biased the overall conclusions of the study.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Knapp, M. J., Knopman, D. S., Solomon, P. R., Pendlebury, W. W., Davis, C. S., & Gracon, S. I. (1994). A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group. JAMA. https://doi.org/10.1001/jama.1994.03510370037029
Vancouver
Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group. JAMA. 1994. doi:10.1001/jama.1994.03510370037029. PMID: 8139083.
BibTeX
@article{knapp1994-8139083,
author = {Knapp, M. J. and Knopman, D. S. and Solomon, P. R. and Pendlebury, W. W. and Davis, C. S. and Gracon, S. I.},
title = {{A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group}},
journal = {JAMA},
year = {1994},
doi = {10.1001/jama.1994.03510370037029},
pmid = {8139083},
url = {https://doi.org/10.1001/jama.1994.03510370037029}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Results A total of 663 patients entered the study; 653 patients were included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30 weeks.
- The results of the ITT analysis revealed significant (P < or = .05) dose-response trends and between-group comparisons on CIBI and ADAS-Cog.
- In evaluable patients, significant dose-response trends were observed for all three primary measures (P < or = .001).
- Significant differences in favor of 160 mg/d of tacrine vs placebo were observed on the CIBI (P < or = .002) and ADAS-Cog and FCCA (P < or = .001), as well as caregiver-global and quality-of-life assessments (P < or = .05).
- On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and evaluable-patient populations, respectively, were rated improved compared with 17% and 18% of placebo patients, respectively.
New to this subject? Start with our plain-English guide: Registered clinical trials →
Study details
- Participants663
- Evidence strengthHigh
How this study scored 79/100
Published in a top-tier journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record and institution's track record, so those were left out: it earned 48 of the 61 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1994 — older than 20 years, still counted |
| Sample size | 2 / 4 | 663 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8139083) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 48 of the 61 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Clinical trials
Also tagged “cholinesterase”
271 studies in the library carry the topic tag “cholinesterase”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 271 tagged studies.