ERS 2022: ALERT 1: COPD and Hospital Management
In the ALERT session (Abstracts Leading to Evolution in Respiratory Medicine Trials), the panel showcased important and very late-breaking clinical trial data from all respiratory disease areas.
Chronic bronchitis is a critical phenotype in patients with COPD; however, currently, available COPD treatments do not address everyday symptoms such as cough and sputum. In addition, evidence suggests the role of Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the pathophysiology of COPD. Icenticaftor is the first-in-class in COPD which aims to restore ion channel function with expected benefits in terms of airway cell function, lung health, and patient benefits. A phase 2B, multicenter, double-blind, placebo-controlled study was conducted to characterize the dose-response relationship of icenticaftor administered orally for 12 weeks on lung function, compared with placebo, when added to triple combination therapy of LABA/LAMA/ICS in patients with COPD, thereby supporting the dose selection for future studies.
The study concluded the following:
- No dose-response for trough FEV1 at week 12
- Icenticaftor demonstrated a favourable safety and tolerability profile
- Icenticaftor 300 mg BID demonstrated a favourable benefits-risk profile supporting further investigation of its therapeutic potential in patients with COPD and chronic bronchitis.
Systemic corticosteroids (SCS) are the universal treatment for COPD exacerbations. However, fewer than 1000 patients have entered a placebo-controlled SCS randomized controlled trial in COPD exacerbations. Corticosteroids are known to increase the risk of mortality. Any short oral CS course is associated with a 5-fold, 3-fold, and 2-fold increased risk for sepsis, venous thromboembolism (VTE), and fracture, respectively. Single-centre proof-of-concept placebo-controlled, double-blind, randomized control trial (BEAT: COPD) has demonstrated that peripheral blood eosinophils can safely direct OCS treatment at the time of a moderate COPD exacerbation. In the STARR2 trial, the intention-to-treat analysis demonstrated that there was no difference in the number of treatment failures in the blood-eosinophil-directed care arm and standard care arm. In addition, no difference was observed in the lung function, COPD Assessment Test (CAT) scores, and Visual analogue scale (VAS) symptoms on day 30. Thus, the STARR2 trial showed that eosinophil-directed prescription in primary care is safe and is not associated with worsened outcomes. Personalized endotype-based treatment with oral prednisolone is possible for patients with COPD and should be part of the clinical guidelines.
Tobacco-exposed symptomatic individuals behave similarly to those with documented airway flow obstruction and have symptoms. Many are currently treated with COPD medications, with a significant proportion being treated with bronchodilators and inhaled corticosteroids. A 12-week, a multicenter, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of indacaterol/ glycopyrrolate 27.5/15.6 mcg administered twice daily in symptomatic current and former smokers with CAT > 10. In the modified intention to treat analysis, 56.4% versus 59% of participants in the intervention and control groups achieved primary outcomes (p=0.65). Four serious adverse events occurred in the treatment group, and 11 occurred in the control group; none were deemed potentially related to the treatment or placebo. Data suggests that long-acting bronchodilators in this population do not improve respiratory symptoms. Therefore, individuals suspected of having COPD must undergo spirometry to understand who will and will not benefit from bronchodilator therapy.
N-acetylcysteine (NAC) is well established as a mucolytic and antioxidant agent for acute and chronic respiratory conditions. IV administration is a convenient route in the hospital setting and may be preferred in certain circumstances, e.g., severely ill hospitalized patients. A large, multicenter, randomized, controlled, subject and rater-blinded study aimed to assess the efficacy of NAC injection in improving sputum viscosity score and expectoration difficulty score in hospitalized patients with abnormal mucus secretion and acute respiratory conditions. NAC IV showed superiority versus placebo in both sputum viscosity and expectoration difficulty scores. In addition, the safety findings confirmed the good tolerability profile of IV NAC 600 mg BID reported from previous small studies, and no new safety concerns were identified. Overall, the study provides new evidence to support the efficacy and safety of IV NAC as a mucolytic and expectorant treatment in clinical situations where the IV route is preferred.
A prospective, parallel-group, randomized clinical trial evaluated the effectiveness of high-flow nasal cannula (HFNC) in comparison to standard noninvasive ventilation (NIV) in patients with acute hypoxemic respiratory failure. 18% of the patients in the HFNC group required invasive mechanical ventilation as compared to 50% of the patients in the NIV group. In addition, the ICU stay, hospital stay and ventilation usage duration were lower in the HFNC group than in the NIV group. HFNC oxygen therapy is a more physiological and promising technique for changing the management of patients with acute and chronic respiratory failure. A growing body of evidence supports its use in acute hypoxemic respiratory failure with better tolerance, lower treatment failure rates, and lower mortality.
The COVI-PRONE randomized clinical trial aimed to determine the efficacy and safety of awake-prone positioning in adults with hypoxemic respiratory failure from COVID-19. The intervention in the study was awake-prone positioning for 8-10 hours per day until there was a 40% reduction in oxygen requirements.
Adherence to the intervention was good but did not meet the target duration of 8-10 hours. No effect on intubation or secondary outcomes was observed.
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
