Gaëtan Deslée1, Hervé Mal2, Hervé Dutau3, Arnaud Bourdin4, Jean Michel Vergnon5, Christophe Pison6, Romain Kessler7, Vincent Jounieaux8, Luc Thiberville9, Sylvie Leroy10, Armelle Marceau2, Sophie Laroumagne3, Jean Pierre Mallet4, Sylvain Dukic11, Coralie Barbe12, Julie Bulsei13, Damien Jolly12, Isabelle Durand-Zaleski13, Charles Hugo Marquette10. 1. Service de Pneumologie, INSERM U903, Hôpital Universitaire de Reims, Reims, France. 2. Service de Pneumologie, Hôpital Universitaire Bichat, Paris, France. 3. Service d'Oncologie Thoracique, Maladies de la Plèvre, Pneumologie Interventionnelle, Hôpital Universitaire de Marseille, Marseille, France. 4. Département de Pneumologie et Addictologie, PhyMedExp, Inserm U1046, CNRS UMR, Hôpital Universitaire de Montpellier, Montpellier, France. 5. Service de Pneumologie, Hôpital Universitaire de Saint-Étienne, Saint-Étienne, France. 6. Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux, Inserm 1055, Hôpital Universitaire de Grenoble Alpes, Grenoble, France. 7. Service de Pneumologie, Hôpital Universitaire de Strasbourg, Strasbourg, France. 8. Service de Pneumologie, Hôpital Universitaire d'Amiens, Amiens, France. 9. Service de Pneumologie, Hôpital Universitaire de Rouen, Rouen, France. 10. Service de Pneumologie, IRCAN, UMR CNRS 7284/Inserm U1081, Team 3, Hôpital Universitaire de Nice Sophia Antipolis, Nice, France. 11. Département de Pharmacovigilance, Hôpital Universitaire de Reims, Reims, France. 12. Département de Méthodologie, Pôle Recherche-Innovations, Hôpital Universitaire de Reims, Reims, France. 13. URC Eco IdF, Unité de Recherche Clinique en Économie de la Santé d'Ile de France, AP-HP Paris, Paris, France.
Abstract
IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual careat 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS: Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95% CI, $47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was $782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.
RCT Entities:
IMPORTANCE: Therapeutic options for severe emphysema are limited. Lung volume reduction using nitinol coils is a bronchoscopic intervention inducing regional parenchymal volume reduction and restoring lung recoil. OBJECTIVE: To evaluate the efficacy, safety, cost, and cost-effectiveness of nitinol coils in treatment of severe emphysema. DESIGN, SETTING, AND PARTICIPANTS: Multicenter 1:1 randomized superiority trial comparing coils with usual care at 10 university hospitals in France. Enrollment of patients with emphysema occurred from March to October 2013, with 12-month follow-up (last follow-up, December 2014). INTERVENTIONS:Patients randomized to usual care (n = 50) received rehabilitation and bronchodilators with or without inhaled corticosteroids and oxygen; those randomized to bilateral coil treatment (n = 50) received usual care plus additional therapy in which approximately 10 coils per lobe were placed in 2 bilateral lobes in 2 procedures. MAIN OUTCOMES AND MEASURES: The primary outcome was improvement of at least 54 m in the 6-minute walk test at 6 months (1-sided hypothesis test). Secondary outcomes included changes at 6 and 12 months in the 6-minute walk test, lung function, quality of life as assessed by St George's Respiratory Questionnaire (range, 0-100; 0 being the best and 100 being the worst quality of life; minimal clinically important difference, ≥4), morbidity, mortality, total cost, and cost-effectiveness. RESULTS: Among 100 patients, 71 men and 29 women (mean age, 62 years) were included. At 6 months, improvement of at least 54 m was observed in 18 patients (36%) in the coil group and 9 patients (18%) in the usual care group, for a between-group difference of 18% (1-sided 95% CI, 4% to ∞; P = .03). Mean between-group differences at 6 and 12 months in the coil and usual care groups were +0.09 L (95% CI, 0.05 L to ∞) (P = .001) and +0.08 L (95% CI, 0.03 L to ∞) (P = .002) for forced expiratory volume in the first second, +21 m (95% CI, -4 m to ∞) (P = .06) and +21 m (95% CI, -5 m to ∞) (P = .12) for 6-minute walk distance, and -13.4 points (95% CI, -8 points to ∞) and -10.6 points (95% CI, -5.8 points to ∞) for St George's Respiratory Questionnaire (1-sided P < .001 for both). Within 12 months, 4 deaths occurred in the coil group and 3 in the usual care group. The mean total 1-year per-patient cost difference between groups was $47,908 (95% CI, $47,879-$48,073) (P < .001); the incremental cost-effectiveness ratio was $782,598 per additional quality-adjusted life-year. CONCLUSIONS AND RELEVANCE: In this preliminary study of patients with severe emphysema followed up for 6 months, bronchoscopic treatment with nitinol coils compared with usual care resulted in improved exercise capacity with high short-term costs. Further investigation is needed to assess durability of benefit and long-term cost implications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822795.
Authors: Wassim W Labaki; Carlos H Martinez; Fernando J Martinez; Craig J Galbán; Brian D Ross; George R Washko; R Graham Barr; Elizabeth A Regan; Harvey O Coxson; Eric A Hoffman; John D Newell; Douglas Curran-Everett; James C Hogg; James D Crapo; David A Lynch; Ella A Kazerooni; MeiLan K Han Journal: Am J Respir Crit Care Med Date: 2017-12-01 Impact factor: 21.405
Authors: Adel Boueiz; Sharon M Lutz; Michael H Cho; Craig P Hersh; Russell P Bowler; George R Washko; Eitan Halper-Stromberg; Per Bakke; Amund Gulsvik; Nan M Laird; Terri H Beaty; Harvey O Coxson; James D Crapo; Edwin K Silverman; Peter J Castaldi; Dawn L DeMeo Journal: Am J Respir Crit Care Med Date: 2017-03-15 Impact factor: 21.405