Journal of Internal Medicine · 2021 · 19 citations · 15 references
MedicineImmunologyPharmacologyImmunotherapyInflammationPulmonary Function TestingAcute Lung InjuryAcute Respiratory Distress SyndromeAnti-inflammatory PharmacologyPulmonary InflammationDurable Clinical ResponseLung Function DeclineLung Function TestingOptimal DesignOxygen Therapy ManagementPneumonia Severity AssessmentRandomized Clinical TrialsTreatment Response Criteria
BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.
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Optimal two-stage designs for phase II clinical trials
Richard Simon · Controlled Clinical Trials · 1989 · 3.6K citations
Norihiro Nishimoto, Kimio Terao, Toru Mima et al. · Blood · 2008 · 810 citations · Full text
Randomized phase II clinical trials.
Richard Simon, R. Wittes, Susan S. Ellenberg · PubMed · 1985 · 470 citations