scholarly journals A trimetazidin hatásosságának összehasonlítása a revaszkularizált és a nem revaszkularizált stabil anginás betegeken a ONECAPS-vizsgálat alapján

2021 ◽  
Vol 162 (29) ◽  
pp. 1167-1171
Author(s):  
János Tomcsányi
Keyword(s):  
Observational Study ◽  
Cardiac Event ◽  
Study Groups ◽  
Canadian Cardiovascular Society ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Short Acting ◽  
Patient Groups

Összefoglaló. Bevezetés: A közelmúltban publikált ATPCI-vizsgálat azt eredményezte, hogy közvetlenül a sikeres revaszkularizáció után alkalmazott trimetazidin biztonságos volt, de nem volt effektívebb a cardiovascularis halál, anginarekurrencia, cardialis hospitalizáció tekintetében, mint a random kettős vakmódszerrel alkalmazott placebo. Célkitűzés: Az általunk korábban végzett ONECAPS nyitott, obszervációs vizsgálat retrospektív analízisét kívántuk elvégezni annak eldöntésére, hogy az anginás betegeknél van-e különbség a trimetazidin prolong hatásosságában annak megfelelően, hogy korábban revaszkularizáció történt. Módszer: 1670, anginás betegből 1008 nem volt revaszkularizálva, míg 662 korábban revaszkularizáción esett át. Az életkorban, társbetegségben nem volt különbség a két csoport között. A betegeknél a heti anginaszámnak és a nitroglicerin-fogyasztásnak, illetve az angina súlyosságának a változását vizsgáltuk a trimetazidin prolong 80 mg napi egyszeri alkalmazása során a revaszkularizált és a nem revaszkularizált betegcsoportban. Eredmények: Mind a revaszkularizált, mind a nem revaszkularizált betegcsoportban szignifikáns csökkenést (p<0,0001) eredményezett a trimetazidin mind a heti anginaszámban, mind a rövid hatású nitroglicerin fogyasztásában. Emellett mindkét betegcsoportban növekedett a Kanadai Cardiovascularis Társaság (CCS) osztályozása szerinti I. súlyosságú angina aránya, és csökkent a CCS III., illetve CCS IV . aránya is. Mindezt a hatást úgy érték el, hogy a revaszkularizált betegeknél 90% felett volt a sztatin, az ACEI/ARB, illetve a béta-blokkoló használata. Következtetés: A trimetazidin prolong napi egyszeri 80 mg adása szignifikánsan csökkenti a heti anginaszámot, nitroglicerin-fogyasztást, illetve az angina súlyosságát. Ezen hatása független attól, hogy a beteg korábban részesült-e revaszkularizációban vagy sem. Orv Hetil. 2021; 162(29): 1167–1171. Summary. Introduction: The recently published ATPCI study resulted in the safety of trimetazidine administered immediately after successful revascularization but was not more effective (cardiovascularis death, recurrence of angina, hospitalization for cardiac event) than the randomized double-blind placebo. Objective: A retrospective analysis of our previously published ONECAPS open-label observational study was performed to determine whether there was a difference in the efficacy of trimetazidin prolong in the angina patients according to whether or not they had previously undergone revascularization. Method: Of the 1670 angina patients, 1008 were not revascularized, while 662 had previously undergone revascularization. There was no difference in age or comorbidity between the two groups. Patients were examined for changes in weekly angina, short-acting nitroglycerin use and angina severity during once-daily administration of trimetazidine prolong 80 mg in revascularized and non-revascularized study groups. Results: In both the revascularized and non-revascularized group, trimetazidine resulted in a significant reduction (p<0.0001) in both weekly angina count and short-acting nitroglycerin use. In addition, the proportion of angina with Canadian Cardiovascular Society (CCS) I increased and the proportion of CCS III and CCS IV decreased in both patient groups as well. All of this effect was achieved with statin, ACEI/ARB, and beta-blocker use above 90% in revascularized patients. Conclusion: Trimetazidine prolong 80 mg once daily significantly reduced the number of angina per week, the use of short-acting nitroglycerin per week, and the severity of angina. This effect is independent of whether the patient has previously received revascularization. Orv Hetil. 2021; 162(29): 1167–1171.

scholarly journals 4564 Nilotinib alters microRNAs that regulate specific autophagy and ubiquitination genes in the cerebrospinal fluid of Parkinson’s patients

2020 ◽  
Vol 4 (s1) ◽  
pp. 99-99
Author(s):  
Alan Fowler ◽  
Yasar Torres-Yhagi ◽  
Fernando Pagan ◽  
Michaeline Hebron ◽  
Barbara Willmarth ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Empirical Bayes ◽  
Controlled Study ◽  
P Value ◽  
Whole Genome ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Open Label Phase

OBJECTIVES/GOALS: Our preclinical data demonstrate that the principal effects of nilotinib, a multi-tyrosine kinase inhibitor, in models of neurodegeneration is clearance of misfolded proteins via autophagy. Here we aimed to evaluate the effects of nilotinib on microRNAs in the cerebrospinal fluid of Parkinson’s disease patients. METHODS/STUDY POPULATION: Cerebrospinal fluid (CSF) was collected as part of an open label phase I (NCT02281474) (n = 12, 300 mg nilotinib taken orally once daily for 6 months), and a phase II randomized, double-blind, placebo-controlled study (NCT02954978) (n = 75, randomized 1:1:1 into placebo, 150 mg or 300 mg nilotinib taken orally once daily for 12 months). RNA was isolated from CSF and Indexed sequencing libraries were prepared from total RNA plus miRNA. Next generation whole-genome sequencing (single-end 1x75 bp, 25 million raw reads per sample) was performed to identify miRNAs significantly differentially expressed (fold-change ≥ 2, Benjamini-Hochberg FDR p-value ≤ 0.05 or Empirical Bayes FDR ≤ 0.05) with treatment compared to baseline. RESULTS/ANTICIPATED RESULTS: Next generation whole-genome sequencing of microRNAs in the CSF demonstrated that nilotinib significantly increases microRNAs that specifically regulate expression of autophagy and ubiquitination genes in individuals with Parkinson’s disease. In the open label phase I, samples, 28 microRNAs found to regulate autophagy and ubiquitination genes, were significantly altered with treatment (Benjamini-Hochberg FDR p-value ≤ 0.05). In the phase II randomized, double-blind, placebo-controlled study samples, we verified several of those 28 candidate microRNAs had been significantly deferentially expressed with treatment (Empirical Bayes FDR p-value ≤ 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data provide robust evidence that nilotinib’s effects on misfolded protein clearance is via autophagy and CSF miRNA sequencing is a valid biomarker of nilotinib’s effects in a definitive phase III study to investigate nilotinib in Parkinson’s and other neurodegenerative diseases. CONFLICT OF INTEREST DESCRIPTION: Charbel Moussa is listed as an inventor on several Georgetown University patents for the use of tyrosine kinase inhibitors as a treatment for neurodegenerative diseases

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

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

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S15) ◽  
pp. 22-30 ◽  
Author(s):  
Timothy E. Wilens ◽  
Thomas J. Spencer ◽  
Joseph Biederman
Keyword(s):  
Extended Release ◽  
Cardiovascular Effects ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Open Label Extension ◽  
Short And Long Term ◽  
Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: A double-blind placebo-controlled trial followed by an open-label extension

2013 ◽  
Vol 28 (6) ◽  
pp. 386-391 ◽  
Author(s):  
I. Manor ◽  
A. Magen ◽  
D. Keidar ◽  
S. Rosen ◽  
H. Tasker ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Rating Scale ◽  
Controlled Trial ◽  
Study Groups ◽  
Open Label ◽  
Double Blind ◽  
Blood Biochemical ◽  
Study Results ◽  
Open Label Extension ◽  
Safety Parameters

AbstractObjective:To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).Methods:Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.Results:One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.Conclusions:Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.

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