Effectiveness and safety of salmeterol/fluticasone fixed-dose combination delivered through Synchrobreathe® in patients with asthma: the real-world EVOLVE study.

BACKGROUND: Inhalation therapy with corticosteroids and long-acting ß2-agonists has been the mainstay of asthma management. However, choosing the correct inhaler technique is essential to effectively deliver the medication to the lungs to attain good asthma control. OBJECTIVE: This study aimed to evaluate asthma control and device usability with salmeterol/fluticasone fixed-dose combination (FDC) administered through Synchrobreathe®, a breath-actuated inhaler (BAI), in Indian patients with persistent asthma (EVOLVE study). DESIGN: The present study was a prospective, open-label, non-comparative, multi-center, observational study. METHODS: The study enrolled 490 patients with documented diagnoses of asthma who were treatment-naive or uncontrolled due to poor inhaler technique associated with a previous device. The primary endpoint was a change from baseline in the Asthma Control Questionnaire-6 (ACQ-6) score at week 12. RESULTS: Mean ACQ-6 score reduced from 2.2 ± 1.07 (baseline) to 0.4 ± 0.49 (mean change: -1.9 ± 1.12, p < 0.0001) at week 12 in the intention-to-treat (ITT) population, and minimal clinically important difference of 0.5 was observed from week 4 onwards. Peak expiratory flow rate improved by 82.5 ± 75.74 ml/min (p < 0.0001) at week 12 in the ITT population. The proportion of well-controlled responders increased from 39.9% (week 4) to 77.1% (week 12). Most (91%) patients preferred the Synchrobreathe® and rated it very high for usability, portability, patient confidence, and satisfaction. Salmeterol/fluticasone FDC administered through Synchrobreathe® was well tolerated. CONCLUSION: Treatment with salmeterol/fluticasone FDC administered through Synchrobreathe® for 12 weeks persistently improved asthma control and lung function and was well tolerated. Most patients were satisfied with it and preferred Synchrobreathe® BAI over their previous device. REGISTRATION: The study was registered with the Clinical Trial Registry of India (CTRI/2018/12/016629).

Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: a randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU)

BackgroundAfter admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. MethodsIn a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n=192) or SoC only (n=195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. ResultsAdherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P=0.063); PP 40.7% RRR, 9.6% ARR (P=0.017); AT 43.2% RRR, 10.8% ARR (P=0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. ConclusionsIn hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.