Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal ...models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients.
ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France.
The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019.
Abstract
Background
It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients′ awareness ...and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages.
Methods
A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher’s exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher’s test. Post-hoc hospital-wise analyses were performed using Fisher’s exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3).
Results
6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105,
p
< 0.001) while the fewest patients were in H-SE (1 %,
N
= 1/100,
p
= 0.001). In addition, 82.5 %, (
N
= 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional.
Conclusions
Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the shade of old pines Frontini, Roberto
American journal of health-system pharmacy,
2016-July-1, 2016-Jul-01, 2016-07-01, 20160701, Letnik:
73, Številka:
13
Journal Article
Recenzirano
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
4.
Biosimilars in der Onkologie Frontini, Roberto
Forum (Heidelberg),
4/2017, Letnik:
32, Številka:
2
Journal Article
In conclusion between a medicine with its active ingredient and the outcome of the patient there are a lot of barriers like e.g. drug formulation, patient attitude, social context, medication errors, ...patient’s genomic, biased information. The pharmacist has to help patients in overcoming such barriers but this is only possible if he or she is part of a cure team working in collaborative way without hierarchy barriers.
The objective of the PHAR-QA (Quality assurance in European pharmacy education and training) project was to investigate how competence-based learning could be applied to a healthcare, sectoral ...profession such as pharmacy. This is the first study on evaluation of competences from the pharmacists' perspective using an improved Delphi method with a large number of respondents from all over Europe. This paper looks at the way in which hospital pharmacists rank the fundamental competences for pharmacy practice. European hospital pharmacists (
= 152) ranked 68 competences for pharmacy practice of two types (personal and patient care), arranged into 13 clusters. Results were compared to those obtained from community pharmacists (
= 258). Generally, hospital and community pharmacists rank competences in a similar way. Nevertheless, differences can be detected. The higher focus of hospital pharmacists on knowledge of the different areas of science as well as on laboratory tests reflects the idea of a hospital pharmacy specialisation. The difference is also visible in the field of drug production. This is a necessary competence in hospitals with requests for drugs for rare diseases, as well as paediatric and oncologic drugs. Hospital pharmacists give entrepreneurship a lower score, but cost-effectiveness a higher one than community pharmacists. This reflects the reality of pharmacy practice where community pharmacists have to act as entrepreneurs, and hospital pharmacists are managers staying within drug budgets. The results are discussed in the light of a "hospital pharmacy" specialisation.
Falsified medicines for human use are an increasing problem in Europe. The
Falsified Medicines Directive (FMD) 2011/62/EU provides measures to prevent the
entry of falsified medicines into the legal ...supply chain by requiring the
placing of safety features consisting of a unique identifier (Ul) and an
anti-tampering device (ATD). Some concerns have arisen from patients regarding
the effectiveness of UI and ATD in terms of safety. In contrast, the relevance
of the supply source as a key point for patients and pharmacists, especially in
hospitals, has not been sufficiently considered by the FMD. Endorsing more Good
Procurement Practices and Good Distribution Practices may be more effective. The
implementation of the FMD in hospitals is wasting human resources and increasing
costs, which will likely result in a poor positive outcome. At both European and
national levels, it is now urgent to mitigate the consequences of the FMD by
updating the legislation.
•Three HPLC methods were established for analyzing a complex mixed suspension.•Extraction procedures for three different active substances were developed.•A new HPLC method in combination with an ...ELSD was developed for the purity analysis of tobramycin.
A suspension comprising of the three antibiotic substances amphotericin B, colistin sulfate and tobramycin sulfate is often used in clinical practice for the selective decontamination of the digestive tract of patients in intensive care. Since no detailed procedures, specifications or stability data are available for manufacturing this suspension, there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this work is to develop a standardized formulation and to determine its stability under defined storage conditions. This would help guarantee that all patients receive the same preparation, therefore ensuring similar efficacy and improved safety. The first step in this process is to develop the required analytical tools to measure the content and purity of the drug substances in this complex mixture. In this paper, the development and validation of these tools as well as the development of the drug suspension formulation is described. The formulation comprises of Ampho-Moronal®-Suspension (Dermapharm) and a buffered, preservated aqueous solution of colistin sulfate and tobramycin sulfate. Two simple, well established high-performance liquid chromatography (HPLC) methods in the European Pharmacopoeia (EP) for impurity profiling of the two active ingredients amphotericin B and colistin sulfate were combined with a newly developed sample extraction procedure for the suspension. Sufficient selectivity and stability-indicating power have been demonstrated. Additionally, a new robust routine method was developed to determine possible degradation products of tobramycin sulfate in the investigated suspension. The specificity, precision, accuracy and linearity of the analytical procedures were demonstrated. The recovery rate was in the range of 90–110%. The precision results for the calculated impurities showed variation coefficients of <10%. The calibration curves were found to be linear with correlation of greater than 0.9994 for all components. The results show the suitability of the methods for the quality control analysis of the suspension.
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