The effect of a trAnSitional Pharmacist Intervention in geRiatric inpatients on hospital visits after dischargE (ASPIRE): Protocol for a randomized controlled trial.

BACKGROUND: Unplanned rehospitalizations occur frequently in older patients. Drug-related problems constitute a major and largely preventable cause with inappropriate prescribing being a substantial culprit. Solutions are needed to reduce this risk by targeting pharmacotherapy both during and after hospital stay. Therefore, we aim to perform a randomized controlled trial in geriatric inpatients to investigate the impact of a multifaceted clinical pharmacy intervention on health-related outcomes. METHODS/DESIGN: The study concerns a monocenter, non-blinded, randomized controlled trial that will take place at the acute geriatric wards of a large academic hospital. Patients being in a palliative stage with active therapy withdrawal or patients discharged to another ward within the same hospital or another hospital are excluded. In total, 828 patients will be randomized (1:1) to the usual care or intervention group. The multifaceted clinical pharmacy intervention comprises medication reconciliation at admission and discharge, medication review, patient/caregiver education, intensified communication with primary care providers and post-discharge follow-up, which also includes a telepharmacology service. The primary endpoint is defined as the time to an all-cause, unplanned hospital revisit within six months after discharge. Other health-related outcomes such as drug-related readmissions, quality of life and number of potentially inappropriate medications will be analyzed as secondary endpoints. Patient inclusion started in February 2021. DISCUSSION: This study will provide useful insights regarding the impact of clinical pharmacy interventions on geriatric wards with the goal to optimize health-related outcomes such as hospital revisits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617340.

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial.

BACKGROUND: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. METHODS: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. FINDINGS: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. INTERPRETATION: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.