Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 2021
Meta AnalysisPharmacological interventions for the prevention of fetal growth restriction: a systematic review and network meta-analysis.
The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. ⋯ Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
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Clin. Pharmacol. Ther. · Jun 2021
COVID-19 and the Emerging Regulatory Guidance for Ongoing Clinical Trials in the European Union.
The coronavirus disease 2019 (COVID-19) pandemic and the accompanying control measures have significantly affected clinical trial (CT) conduct, and sponsors have needed to make rapid changes to their CT operations. As a result, regulatory guidance was pivotal during the initial phases of the pandemic. This study aimed to evaluate the regulatory readiness and guidance related to COVID-19 in the European Union (EU). ⋯ The time from the first European COVID-19 case to the first published EMA guidance was 56 days and ranged from 47 to 66 days for the first national guidances. Guidance was provided most frequently for regulatory management (24/24), safety management (23/24), documentation management (22/24), and CT monitoring (22/24). The regulatory guidance provided during the pandemic, ensuring participant safety and data integrity, may now be the starting point to innovate future CT conduct.
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Clin. Pharmacol. Ther. · Jun 2021
Observational StudyEffect of Corticosteroids on Mortality in Hospitalized COVID-19 Patients Not Receiving Invasive Mechanical Ventilation.
The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. ⋯ COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.
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Clin. Pharmacol. Ther. · Apr 2021
Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database.
Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) and authorized conditionally by the European Medicines Agency (EMA) for patients with coronavirus disease 2019 (COVID-19). Its benefit-risk ratio is still being explored because data in the field are rather scant. A decrease of the creatinine clearance associated with remdesivir has been inconstantly reported in clinical trials with unclear relevance. ⋯ ROR of ARF with remdesivir was 20-fold (20.3; confidence interval 0.95 [15.7-26.3], P < 0.0001]) that of comparative drugs. Based on ARF cases reported in VigiBase, and despite the caveats inherent to COVID-19 circumstances, we detected a statistically significant pharmacovigilance signal of nephrotoxicity associated with remdesivir, deserving a thorough qualitative assessment of all available data. Meanwhile, as recommended in its Summary of Product Characteristics, assessment of patients with COVID-19 renal function should prevail before and during treatment with remdesivir in COVID-19.
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Clin. Pharmacol. Ther. · Apr 2021
ReviewKey Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock.
Early initiation of effective antibiotic therapy is vitally important for saving the lives of critically ill patients with sepsis or septic shock. The susceptibility of the infecting pathogen and the ability of the selected dosage regimen to safely achieve the required antibiotic exposure need to be carefully considered to achieve a high probability of a successful outcome. Critically ill patients commonly experience substantial pathophysiological changes that impact the functions of various organs, including the kidneys. ⋯ Two common conditions that very substantially complicate the use of antibiotics in critically ill patients with sepsis, unstable renal function, and augmented renal clearance, are considered in detail and their potential therapeutic implications are explored. Suggestions are provided on how treatment of bacterial infections in critically ill patients with sepsis might be improved. Of high potential are model-informed approaches that aim to individualize initial treatment regimens based on patient and bacterial characteristics, with refinement of regimens during treatment in response to monitoring antibiotic concentrations, responsive measures of renal function, and other important clinical data.