MISSING DATA AND DROPOUTS IN A LONG-TERM, DOUBLE-BLIND SCHIZOPHRENIA STUDY COMPARING ZIPRASIDONE AND HALOPERIDOL

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

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Long-term effects of a modified, low-protein infant formula on growth and body composition: Follow-up of a randomized, double-blind, equivalence trial

Clinical Nutrition ◽

10.1016/j.clnu.2021.04.034 ◽

2021 ◽

Author(s):

Stefanie M.P. Kouwenhoven ◽

Nadja Antl ◽

Martijn J.J. Finken ◽

Jos W.R. Twisk ◽

Eline M. van der Beek ◽

...

Keyword(s):

Body Composition ◽

Infant Formula ◽

Long Term Effects ◽

Double Blind ◽

Equivalence Trial ◽

Low Protein

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Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01751-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Peter Witters ◽

Andrew C. Edmondson ◽

Christina Lam ◽

Christin Johnsen ◽

Marc C. Patterson ◽

...

Keyword(s):

Clinical Trials ◽

Natural History ◽

Randomized Study ◽

Short Term ◽

Double Blind ◽

Natural History Study ◽

Natural History Studies ◽

Carbohydrate Deficient Transferrin ◽

Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

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Topical Benzyl Alcohol Reduces Cataract Surgery Need: Two Long-Term Double Blind Studies

Journal of Ocular Pharmacology and Therapeutics ◽

10.1089/jop.1987.3.211 ◽

1987 ◽

Vol 3 (3) ◽

pp. 211-225 ◽

Cited By ~ 6

Author(s):

M. TESTA ◽

G. IULIANO ◽

P. MORTON ◽

A. LONGONI

Keyword(s):

Cataract Surgery ◽

Benzyl Alcohol ◽

Double Blind

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Impacts of treatments on recurrence and 28-year survival of ischemic stroke patients

Scientific Reports ◽

10.1038/s41598-021-94757-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Ann Wang ◽

Tzy-Haw Wu ◽

Shin-Liang Pan ◽

Hsiu-Hsi Chen ◽

Sherry Yueh-Hsia Chiu

Keyword(s):

Ischemic Stroke ◽

Cerebrovascular Disease ◽

Cox Regression ◽

Controlled Trial ◽

Stroke Recurrence ◽

Long Term Effects ◽

Stroke Patients ◽

Double Blind ◽

Term Survival

AbstractAspirin and nicametate are well-established therapies for preventing recurrence and mortality from stroke in patients diagnosed as ischemic stroke. However, their respective effects on the recurrence, making allowance for the duration of recurrence and death without the occurrence of recurrence, and long-term survival have not been well elucidated. We aimed to evaluate long-term effect of two kinds of treatment on cerebrovascular death among ischemic stroke patients with or without the recurrence of stroke. Data used in this study were derived from the cohort based on a multicenter randomized double-blind controlled trial during 1992 to 1995 with the enrollment of a total of 466 patients with first-time non-cardioembolic ischemic stroke who were randomly allocated to receive aspirin (n = 222) or nicametate (n = 244). The trial cohort was followed up over time to ascertain the date of recurrence within trial period and death until Sep of 2019. The time-dependent Cox regression model was used to estimate the long-term effects of two treatments on death from cerebrovascular disease with and without recurrence. A total of 49 patients experienced stroke recurrence and 89 cerebrovascular deaths was confirmed. Patients treated with nicametate were more likely, but non statistically significantly, to have recurrence (aHR: 1.73, 95% CI 0.96–3.13) as compared with those treated by aspirin. Nicametate reduced the risk of cerebrovascular death about 37% (aHR: 0.63, 95% CI 0.41–0.97) compared with aspirin. The aspirin group had a lower recurrence rate than the nicametate group even with recurrence after 1–2 years of follow-up of first stroke but the latter had significantly reduced death from cerebrovascular disease for nicametate group, which requires more research to verify.

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