Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial.
Jens Vogel-ClaussenChristian-Olaf SchönfeldTill F KaireitAndreas VoskrebenzevChristoph P CzernerJulius RenneHanns-Christian TillmannKorbinian BerschneiderSimone HiltlJohann BauersachsTobias WelteJens M HohlfeldPublished in: American journal of respiratory and critical care medicine (2020)
Rationale: In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. Objectives: To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. Methods: In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Measurements and Main Results: Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 μg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF (P = 0.006) and regional PMBF (P values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo (P = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; P = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo (P < 0.0001). Conclusions: Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).
Keyphrases
- double blind
- placebo controlled
- phase iii
- clinical trial
- magnetic resonance imaging
- blood flow
- respiratory failure
- phase ii
- contrast enhanced
- open label
- left ventricular
- study protocol
- mechanical ventilation
- pulmonary hypertension
- end stage renal disease
- chronic obstructive pulmonary disease
- ejection fraction
- diffusion weighted imaging
- lung function
- newly diagnosed
- randomized controlled trial
- blood pressure
- chronic kidney disease
- peritoneal dialysis
- magnetic resonance
- prognostic factors
- computed tomography
- aortic stenosis
- cystic fibrosis
- hypertrophic cardiomyopathy
- heart failure
- extracorporeal membrane oxygenation
- intensive care unit
- acute coronary syndrome
- physical activity
- transcatheter aortic valve replacement
- data analysis
- percutaneous coronary intervention