Juan F Masa1, Iván Benítez2, Maria Á Sánchez-Quiroga3, Francisco J Gomez de Terreros4, Jaime Corral4, Auxiliadora Romero5, Candela Caballero-Eraso5, Maria L Alonso-Álvarez6, Estrella Ordax-Carbajo6, Teresa Gomez-Garcia7, Mónica González8, Soledad López-Martín9, José M Marin10, Sergi Martí11, Trinidad Díaz-Cambriles12, Eusebi Chiner13, Carlos Egea14, Javier Barca15, Francisco J Vázquez-Polo16, Miguel A Negrín16, María Martel-Escobar16, Ferrán Barbé2, Babak Mokhlesi17. 1. Respiratory Department, San Pedro de Alcántara Hospital, Cáceres, Spain; CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain. Electronic address: fmasa@separ.es. 2. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Institut de Recerca Biomédica de LLeida (IRBLLEIDA), Lleida, Spain. 3. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain; Respiratory Department, Virgen del Puerto Hospital, Plasencia, Cáceres, Spain. 4. Respiratory Department, San Pedro de Alcántara Hospital, Cáceres, Spain; CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain. 5. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Sevilla, Spain. 6. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, University Hospital, Burgos, Spain. 7. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, IIS Fundación Jiménez Díaz, Madrid, Spain. 8. Respiratory Department, Valdecilla Hospital, Santander, Spain. 9. Respiratory Department, Gregorio Marañón Hospital, Madrid, Spain. 10. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Miguel Servet Hospital, Zaragoza, Spain. 11. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Vall d'Hebron Hospital, Barcelona, Spain. 12. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Doce de Octubre Hospital, Madrid, Spain. 13. Respiratory Department, San Juan Hospital, Alicante, Spain. 14. CIBER de enfermedades respiratorias (CIBERES), Madrid, Spain; Respiratory Department, Alava University Hospital IRB, Vitoria, Spain. 15. Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Badajoz, Spain; Nursing Department, Extremadura University, Cáceres, Spain. 16. Department of Quantitative Methods, Las Palmas de Gran Canaria University, Canary Islands, Spain. 17. Department of Medicine/Pulmonary and Critical Care, University of Chicago, IL.
Abstract
BACKGROUND:Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. RESEARCH QUESTION: Is NIV effective in OHS without severe OSA phenotype? STUDY DESIGN AND METHODS: In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups. RESULTS:Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. INTERPRETATION: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe OSA phenotype. RESEARCH QUESTION: Is NIV effective in OHS without severe OSA phenotype? STUDY DESIGN AND METHODS: In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients' enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups. RESULTS: Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms. INTERPRETATION: In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov.
Authors: A Léotard; M Delorme; S Hartley; C Khouri; M Lebret; F Lofaso; J-L Pepin; J-C Borel Journal: Sleep Breath Date: 2022-06-20 Impact factor: 2.816
Authors: Ruth Sobala; Hannah Carlin; Thomas Fretwell; Sufyan Shakir; Katie Cattermole; Amy Royston; Paul McCallion; John Davison; Joanna Lumb; Hilary Tedd; Ben Messer; Anthony De Soyza Journal: ERJ Open Res Date: 2022-04-19