American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jul 2023
Randomized Controlled TrialEfficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of PATHWAY and NAVIGATOR Studies.
Rationale: Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric oxide levels, and irrespective of allergy status, in the phase 2b PATHWAY (Study to Evaluate the Efficacy and Safety of MEDI9929 [AMG 157] in Adult Subjects With Inadequately Controlled, Severe Asthma; NCT02054130) and phase 3 NAVIGATOR (Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma; NCT03347279) trials. Objectives: To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR. Methods: PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled trials with similar designs. ⋯ The incidence of adverse events was similar between treatment groups. Conclusions: Tezepelumab resulted in clinically meaningful reductions in exacerbations and improvements in other outcomes in patients with severe, uncontrolled asthma, across clinically relevant subgroups. Clinical trials registered with www.clinicaltrials.gov (NCT02054130 [PATHWAY], NCT03347279 [NAVIGATOR]).
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Am. J. Respir. Crit. Care Med. · Jul 2023
Multicenter StudyLung RecruitmEnt Assessed by EleCtRical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 ARDS.
Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. ⋯ Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).
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Am. J. Respir. Crit. Care Med. · Jul 2023
Randomized Controlled TrialStructured Mobilization for Critically Ill Patients: A Pragmatic Cluster-Randomized Trial.
Rationale: Small trials and professional recommendations support mobilization interventions to improve recovery among critically ill patients, but their real-world effectiveness is unknown. Objective: To evaluate a low-cost, multifaceted mobilization intervention. Methods: We conducted a stepped-wedge cluster-randomized trial across 12 ICUs with diverse case mixes. ⋯ ICU mortality (31.5% vs. 29.0%), falls (0.7% vs. 0.4%), and unplanned extubations (2.0% vs. 1.8%) were similar between groups (all P > 0.3). Conclusions: A low-cost, multifaceted mobilization intervention did not improve overall mobility but improved patients' odds of standing and was safe. Clinical trial registered with www.clinicaltrials.gov (NCT03863470).
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Am. J. Respir. Crit. Care Med. · Jul 2023
Clinical TrialInterventions Relieving Dyspnea in Intubated Patients Show Responsiveness of the Mechanical Ventilation - Respiratory Distress Observation Scale.
Rationale: Breathing difficulties are highly stressful. In critically ill patients, they are associated with an increased risk of posttraumatic manifestations. Dyspnea, the corresponding symptom, cannot be directly assessed in noncommunicative patients. ⋯ MV-RDOS scores were higher in patients with EEG preinspiratory potentials (4.9 [IQR, 4.2-6.3] vs. 4.0 [IQR, 2.1-4.9]; P = 0.002). Conclusions: The MV-RDOS seems able to detect and monitor respiratory symptoms reasonably well in noncommunicative intubated patients. Clinical trial registered with www.clinicaltrials.gov (NCT02801838).
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Am. J. Respir. Crit. Care Med. · Jul 2023
Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ≥6 Years with Cystic Fibrosis and At Least One F508del Allele: A Phase 3, Open-Label Clinical Trial.
Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. ⋯ Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX/TEZ/IVA in this pediatric population. Clinical trial registered with www.clinicaltrials.gov (NCT04183790).