Chest
Volume 158, Issue 3, September 2020, Pages 1176-1186
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Sleep: Original Research
Long-term Noninvasive Ventilation in Obesity Hypoventilation Syndrome Without Severe OSA: The Pickwick Randomized Controlled Trial

https://doi.org/10.1016/j.chest.2020.03.068Get rights and content
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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 ;

Key Words

CPAP
noninvasive ventilation
obesity hypoventilation syndrome
sleep apnea

Abbreviations

6MWD
6-min walk distance
ESS
Epworth Sleepiness Scale
HCO3
bicarbonate
IQR
interquartile range
NIV
noninvasive ventilation
OHS
obesity hypoventilation syndrome
PAP
positive airway pressure
SF-36
36-Item Short Form Health Survey

Cited by (0)

FUNDING/SUPPORT: This study was supported by the Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo) [Grant PI050402], the Spanish Respiratory Foundation 2005 (FEPAR), and Air Liquide Spain.

Collaborators from the Spanish Sleep Network are listed in the Acknowledgments.