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This double-blind, randomized, placebo-controlled parallel-group multicenter pilot study will investigate the effects and safety of different doses of intranasal MDZ for the treatment of anxiety in palliative care patients. Adult palliative care patients  with self-reported acute anxiety and clinical indication for benzodiazepine treatment will receive either placebo or one of two different midazolam doses applied as intranasal spray. The primary outcome will be patient-reported levels of anxiety before and 30 minutes after study drug administration. Levels of sedation, time to first additional dose and cumulative number of additional doses for the following 24 hours will be secondary outcome parameters. In a subset of patients, basic pharmacokinetic parameters of intranasal midazolam will be assessed.

Study team:    Manuel Haschke, Carla Meyer-Massetti, Ursina Wernli, Steffen Eychmüller, Caroline Hertler, Andreas Major
Funding:         Internal funds, applications for external funding pending
Status:            In preparation

This study aims to investigate differences between nicotine salt and free-base nicotine solutions with similar nicotine concentration as well as between high and low nicotine salt concentrations used in electronic cigarettes. Investigations include differences in the nicotine blood concentration, subjective effects and vital signs. The findings can be useful in the future in the context of smoking cessation, since satisfactory substitutes for tobacco cigarettes that can efficiently deliver nicotine without combustion of tobacco can reduce smoking cravings and may represent a smoking cessation aid for smokers willing to quit.

Study team:  Evangelia Liakoni (PI), Samuel Christen, Manuel Haschke
Funding:         internal (CTU Bern)
Status:            Study completed, data analysis
Status registration: Clinical Trials

In this study, smokers willing to quit will be randomly divided into groups that will receive double-blinded e-cigarettes with a low and a high nicotine concentration for three months and a control group. Since smokers adjust their daily nicotine intake in order to maintain desired levels of nicotine in their body, a higher nicotine concentration in the e-liquid might benefit smokers who are seeking to quit not only by providing sufficient nicotine blood levels to reduce craving and relapse, but also by reducing exposure to other potentially toxic compounds contained in the e-liquid.

Study team:   Evangelia Liakoni (PI), Samuel Christen, Manuel Haschke
Funding:        SNF
Status:           Recruiting
Study registration: Clinical Trials

In this project (collaboration between the departments of Clinical Pharmacology & Toxicology, Internal Medicine, and Anesthesiology/Pain Medicine) the effect of blinded withdrawal of paracetamol in cancer patients with chronic pain under strong opiods will be investigated. This combination is recommended in the third step of the WHO analgesic ladder, despite the absence of high-quality evidence to support it. In case the study shows that paracetamol is not superior to placebo, it will have a broad impact on the management of chronic pain patients, both by reducing their pill burden and eliminating the risk of paracetamol-associated (hepato)toxicity.

Study team:   Evangelia Liakoni (PI), Christina Kotoula, Konrad Streitberger, Maria Wertli
Funding:        SNF
Status:           Recruiting
Study registration: Clinical Trials

The Broad One-Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) project aims to cut malaria transmission by delivering the broad-spectrum antiparasitic ivermectin to humans and livestock in the form of mass drug deliveries during the rainy seasons. Ivermectin has an excellent safety profile in humans but acts as an endectocide and is lethal for the malaria transmitting vector, Anopheles. Trial sites are in Mozambique and Tanzania. The project will not only evaluate the safety and efficacy of the intervention. It will also consider the entomological, health economic, veterinary, sociological, and environmental impact of such an intervention.

Study team:   Felix Hammann (PI), Charlotte Kern, Verena Schöning, Urs Duthaler (University of Basel)
Funding:         Unitaid
Status:            ongoing

Links / Publications

• Projekt-Webseite
• UNITAID
• Malar J. 2023 Jun 24;22(1):194
• Trials. 2023 Feb 21;24(1):128
• Parasit Vectors. 2021 Mar 20;14(1):172
• PLoS Pathog. 2021 Mar 17;17(3):e1009382
• EClinicalMedicine. 2021 Feb;32:100720
  • Sci Rep. 2020 Oct 13;10(1):17073
• Trials. 2020 Jun 8;21(1):498
  • Am J Trop Med Hyg. 2020 Jun;102(6):1156-1157
• J Antimicrob Chemother. 2020 Feb 1;75(2):438-440
• Br J Clin Pharmacol. 2019 Mar;85(3):626-633

The Insel Hospital Group hosts an extensive data warehousing service with detailed electronic health records. As part of our mission to provide patients with safe and optimized drug therapies, we established an automated system that regularly analyzes the medical history and drug regimens of patients in the wards of the Dept. of General Internal Medicine. Among other things, the system monitors critical laboratory markers of organ function, suggests dose adaptations, checks for drug-drug interactions, and potentially inappropriate medications in the elderly. We continuously maintain and develop this software platform, and adapt it to new challenges such as new drug therapies that emerged during the COVID-19 pandemic, or drugs that have recently been brought to market.

Study team:   Felix Hammann (PI), Verena Schöning, Charlotte Kern, Manuel Haschke
Funding:         internal
Status:            ongoing

Links / Publications

• Pharmaceutics. 2022 Aug 30;14(9):1828
• Swiss Med Informatics. 2022;(01-2021-SMI)
• J Transl Med. 2022 Sep 23;20(1):427
• Front Med (Lausanne). 2022 May 17;9:890661
• J Transl Med. 2021 Feb 5;19(1):56

Pharmacometric methods allow us to tailor a patient’s drug therapy to their specific needs. From the first dose through dose adaptations made necessary by changes to treatment plans or concomitant disease, we support and inform prescribers across the Insel Hospital Group as well as external health care providers. Ongoing national and international research collaborations cover beta-lactams, aminoglycosides, and other antibiotics. With most dosing recommendations currently performed on an ad-hoc basis, we are currently deploying a platform for desktop and mobile use both in routine clinical care and in clinical trial situations. Previous projects have included characterizations of SARS-CoV-2 viral kinetics to predict the efficacy of novel antiviral therapies against COVID-19, and machine learning prediction models for COVID-19 clinical outcome (a tool used productively in patient triage.

Study team:   Felix Hammann (PI), Verena Schöning
Funding:        UNITAID, Leenaards Foundation, internal
Status:           ongoing

Links / Publications:

• Pharmaceutics. 2022 Aug 30;14(9):1828 
• Front Pharmacol. 2022 Feb 9:13:816429
• Front Pharmacol. 2021 Mar 10:12:625678

This randomized, double-blind, controlled trial will assess whether metamizole is non-inferior to ibuprofen in a new episode of acute or subacute LBP and whether a short educational intervention including evidence-based patient information is superior to usual care alone. Adult patients seeking care for new onset of non-specific or specific low back pain where the primary care physician plans to prescribe an non-opioid pain medication are randomized into four groups: metamizole or ibuprofen either with educational intervention or standard care. The primary outcomes are the change in pain (NRS, range 0-10) from baseline to follow-up at day 14 and the change in the Core Outcome Measures Index (COMI) sum-score (range 0-10) from baseline to follow-up at day 42.

Study team:    Maria Wertli (PI), Manuel Haschke
Funding:         SNF
Status:            recruiting
study registration: Clinical Trials

The aims of this multi-part project were to investigate the toxicity mechanisms leading to metamizole-induced neutropenia by assessing metabolic/direct toxicity of primary or secondary metamizole metabolites on human granulocytes and granulocyte progenitors and by assessing a possible involvement of the adaptive immune system.  In addition, it aimed to identify potential genetic susceptibility markers by combining a targeted, comprehensive investigation of HLA genomic regions often implicated in immune-mediated drug reactions and a genome-wide analysis of genetic variation comparing a case cohort of patients who suffered metamizole-induced agranulocytosis with metamizole-tolerant and matched population controls.

Study team:    Manuel Haschke (PI), Stephan Krähenbühl, Ursula Amstutz, Daniel Yerli
Funding:         SNF
Status:            completed

This open-label, nonrandomized, sequential treatment interaction study investigated the effect of a CYP3A4- and p-gylcoprotein inducing H. perforatum extract on the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy volunteers. Rivaroxaban plasma concentrations and inhibition of the activated coagulation factor X (factor Xa) activity were measured prior to and up to 48 h after a single dose of 20mg rivaroxaban before and after 2 weeks of treatment with the H. perforatum extract. Before and after induction, CYP3A4 and p-glycoprotein were phenotyped with midazolam and fexofenadine, respectively, and all study participants were genotyped for p-gp variants 2677G > T/A (rs2032582) and 3435C > T (rs1045642). H. perforatum extract reduced geometric mean ratios for AUC and Cmax of rivaroxaban and AUEC for inhibition of factor Xa activity to 0.76 (90% CI 0.70, 0.82), 0.86 (90% CI 0.76, 0.97), and 0.80 (90% CI 0.71, 0.89), respectively.

Study team:    Stephan Krähenbühl, Evangelia Liakoni, Felix Hammann, Manuel Haschke
Funding:         Internal funds, Bayer Schweiz
Status:            completed
Study registration: Clinical Trials

Medical and biological properties of drugs are often very close related to their structure. We have been supporting the discovery of new drugs – and unknown activities of existing drugs (drug repurposing) – using machine learning since the late 2000s. Using a quantitative structure-activity relationship (QSAR) models with a wide range of artificial intelligence methods, we cover drug activity, toxicities / adverse effects, and basic pharmacological properties such as oral absorption, membrane passage, and metabolism.

Study team:   Felix Hammann, Verena Schöning
Funding:        Altana, UNITAID, internal funds
Status:           ongoing

Links / Publications  (selected):

• Molecules. 2021 Oct 28;26(21):6508
• Expert Opin Drug Discov. 2018 Dec;13(12):1067-1069
• J Chem Inf Model. 2011 Oct 24;51(10):2690-6
• Clin Pharmacol Ther. 2010 Jul;88(1):52-9
• Curr Drug Metab. 2009 May;10(4):339-46