American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled Trial Multicenter StudyAn All-Oral 6-Month Regimen for Multidrug-Resistant TB (the NExT Study): A Multicenter, Randomized Controlled Trial.
Rationale: Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives: To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods: Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. ⋯ However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT02454205).
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled TrialEarly Bactericidal Activity of Meropenem Plus Clavulanate (+/-Rifampin) For TB: The COMRADE Randomized, Phase 2 Trial.
Rationale: Carbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain. Objectives: To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin. ⋯ This difference was only detectable with solid culture. Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens. Clinical trial registered with www.clinicaltrials.gov (NCT03174184).
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled Trial Multicenter StudyRandomised Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.
Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. ⋯ Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled Trial Multicenter StudyPhase 2b Study of Inhaled RVT-1601 for Chronic Cough in Idiopathic Pulmonary Fibrosis: SCENIC Trial: Multi-Center, Randomized, Placebo-Controlled Study.
Rationale: Chronic cough remains a major and often debilitating symptom for patients with idiopathic pulmonary fibrosis (IPF). In a phase 2A study, inhaled RVT-1601 (cromolyn sodium) reduced daytime cough and 24-hour average cough counts in patients with IPF. Objectives: To determine the efficacy, safety, and optimal dose of inhaled RVT-1601 for the treatment of chronic cough in patients with IPF. ⋯ The mean percentage change from baseline in 24-hour average cough count was 27.7% in the placebo group. Treatment was generally well tolerated. Conclusions: Treatment with inhaled RVT-1601 (10, 40, and 80 mg three times a day) did not provide benefit over placebo for the treatment of chronic cough in patients with IPF.
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled TrialImpact of Exposure to Diesel Exhaust on Inflammation Markers and Proteases in Former Smokers with COPD: A Randomized, Double-Blinded, Crossover Study.
Rationale: There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure. Objectives: To document the impact of short-term air pollution exposure on inflammation markers, proteases, and antiproteases in the lower airways of older adults with and without COPD. Methods: Thirty participants (10 ex-smokers with mild to moderate COPD and 20 healthy participants [9 ex-smokers and 11 never-smokers]), with an average age of 60 years, completed this double-blinded, controlled, human crossover exposure study. ⋯ Circulating lymphocytes were increased after DE exposure (0.14 [95% CI, 0.05-0.24] cells × 109/L; P = 0.03), irrespective of COPD status. Conclusions: A controlled human crossover study of DE exposure reveals that former smokers with COPD may be susceptible to an inflammatory response compared with ex-smokers without COPD or never-smoking healthy control participants. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).