B Maitre1,2,3,4, M Djibre5,6, S Katsahian7,8, A Habibi7,9, K Stankovic Stojanovic10, M Khellaf7,9, I Bourgeon11,12, F Lionnet6,10, A Charles-Nelson7,8, L Brochard11,13, F Lemaire11,12, F Galacteros7,14, C Brun-Buisson11,12, M Fartoukh12,5,6, A Mekontso Dessap11,12. 1. AP-HP, Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Créteil, 94010, France. antenne.pneumo@hmn.aphp.fr. 2. UPEC, Faculté de Médecine, GRC CARMAS, Créteil, 94010, France. antenne.pneumo@hmn.aphp.fr. 3. Centre Hospitalier Intercommunal de Créteil, DHU A-TVB, Service de Pneumologie et Pathologie Professionnelle, Créteil, 94010, France. antenne.pneumo@hmn.aphp.fr. 4. Unité de Pneumologie, Service de Réanimation Médicale, CHU Henri Mondor, 51 Av Mal de Lattre de Tassigny, 94 010, Créteil Cedex, France. antenne.pneumo@hmn.aphp.fr. 5. AP-HP, Hôpitaux Universitaires de l'Est Parisien, Hôpital Tenon, Pôle Thorax Voies aériennes, Unité de Réanimation Médico-chirurgicale, Paris, France. 6. Sorbonne Universités UPMC, Paris 06, France. 7. UPEC, Faculté de Médecine, Créteil, 94010, France. 8. AP-HP, Groupe Henri Mondor, Unité de Recherche Clinique, Créteil, 94010, France. 9. AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Interne, Créteil, 94010, France. 10. AP-HP, Hôpitaux Universitaires de l'Est Parisien, Hôpital Tenon, Service de Médecine interne, Centre de Référence de la Drépanocytose Adulte, Paris, 75020, France. 11. AP-HP, Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Créteil, 94010, France. 12. UPEC, Faculté de Médecine, GRC CARMAS, Créteil, 94010, France. 13. Interdépartemental Division of Critical Care Medicine, St. Michael's Hospital, Toronto, ON, Canada. 14. AP-HP, Groupe Henri-Mondor, Unité des Maladies du Globule Rouge, DHU A-TVB, Créteil, 94010, France.
Abstract
PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients withhypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS:iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.
RCT Entities:
PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS:iNO did not reduce the rate of treatment failure in adult SCDpatients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.
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