Randomized Controlled Trial Between Auto-titration and Manual Titration of Non-invasive Ventilation in Obesity Hypoventilation Syndrome

Overview

Primary Objectives: To evaluate the effectiveness in the obesity hypoventilation syndrome (OHS) treatment with non-invasive ventilation (NIV) set manually by polysomnography compared to the same treatment with a respirator with automatic NIV adjustment, analyzing as primary variable PaCO2 and as operational variables dropout rate for medical reasons and mortality. Secondary objectives: cost-effectiveness, clinical and functional improvement in wakefulness and during sleep, quality of life, blood pressure monitoring for 24 hours, incidence and evolution of cardiovascular events and use of health resources. Other objectives: 1) effectiveness of treatments in the following subgroups of patients: gender, age, socioeconomic status, severity of sleep apnea, VNI compliance, quality of life and comorbidities; 2) To evaluate the profile of patients with poor adherence to NIV based on clinical severity, gender, age and socioeconomic status in the whole sample and in both intervention groups.

Full Title of Study: “Effectiveness of Noninvasive Ventilation Adjusted Automatically in the Obesity Hypoventilation Syndrome”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: July 1, 2023

Detailed Description

Method: Prospective, blind researchers, randomized, controlled non-inferiority and cost-effectiveness relationship, with two parallel open groups. 200 OHS patients will be divided into two groups by simple randomization 1:1 and followed for one year. The premise of non-inferiority is -2 at the lower limit of the confidence interval 95% for the change in PCO2 between the arms being assessed by analysis of covariance, adjusted for 2-sided, age, sex, body mass index in intention-to-treat and per-protocol analysis. The cost-effectiveness will be performed by Bayesian techniques with sensitivity analysis.

Interventions

  • Device: Manual Non invasive ventilation titration
    • Manual Group: during a complete polysomnography, adding transcutaneous capnography and the basic ventilators curves, the ventilators setting will be adjusted in order to correct respiratory events and patient-ventilator asyncrony. A 10 hours face-to-face investigator training meeting is programmed before opening the inclusion period.
  • Device: Automatic Non invasive ventilation titration
    • Automatic Group: the A40 ventilator in the automatic AVAPS mode will be adjusted in order to achieve 8-10 ml/kg of ideal weight.

Arms, Groups and Cohorts

  • Active Comparator: Manual
    • In this group non invasive mechanical ventilation will be manually titrated during a polysomnography. The Philips A40 ventilator will be used in Spontaneous-Timed (ST) mode.
  • Active Comparator: Automatic
    • In this group the ventilator will run in an automatic mode (AVAPS) with the same Phillips A40 ventilator.

Clinical Trial Outcome Measures

Primary Measures

  • Change in PaCO2 between arms
    • Time Frame: 1 year
    • Arterial blood gases while room air breathing expressed in mmHg

Secondary Measures

  • Cost-effectiveness analysis by primary outcome
    • Time Frame: 1 year
    • Cost-effectiveness analysis based on the primary outcome in mmHg Differences in within trial costs will be related with the differences in effectiveness (primary outcome) between arms using a probabilistic Bayesian approach to calculate the cost-effectiveness plane.
  • Cost-effectiveness analysis by QALY
    • Time Frame: 1 year
    • Cost-effectiveness analysis based on the quality adjusted life year (QALY) Differences in within trial costs will be related with the differences in effectiveness (QALY) between arms using a probabilistic Bayesian approach to calculate the cost-effectiveness plane.
  • Change in subjective daytime sleepiness
    • Time Frame: 1 year
    • Sleepiness evaluated by Epworth sleepiness scale, range from 0 to 24, being 0 the best result and 24 the worst.
  • Change in Quality of life measured by Functional Sleep Outcomes of Sleep Questionnaire (FOSQ)
    • Time Frame: 1 year
    • Quality of life measured by Functional Sleep Outcomes of Sleep Questionnaire (FOSQ), range from 0 to 120, being 0 the worst result and 120 the best result .
  • Change in Quality of life measured by visual analogical wellbeing scale (VAWS)
    • Time Frame: 1 year
    • Quality of life measured by visual analogical well-being scale (VAWS), range from 0 to 100, being 0 the worst result and 120 the best result .
  • Change in Quality of life measured by Euroqol 5D.
    • Time Frame: 1 year
    • Quality of life measured by Euroqol 5D, range from 0 to 1, being 0 the worst result and 1 the best result .
  • Change in Quality of life measured by Short Form-36 (SF36), Mental component
    • Time Frame: 1 year
    • Quality of life measured by Short Form-36 (SF36) Mental component,range from 0 to 100, being 0 the worst result and 100 the best result.
  • Change in Quality of life measured by Short Form-36 (SF36), Physical component
    • Time Frame: 1 year
    • Quality of life measured by Short Form-36 (SF36) Physical component,range from 0 to 100, being 0 the worst result and 100 the best result.
  • Change in Bicarbonate arterial blood concentration
    • Time Frame: 1 year
    • Arterial blood gases while breathing room air expressed in mmol/L
  • Change in PaO2
    • Time Frame: 1 year
    • Arterial blood gases while breathing room air expressed PaO2 in mmHg
  • Change in pH
    • Time Frame: 1 year
    • Arterial blood gases while breathing room air
  • Change in polysomnographic Sleep periods
    • Time Frame: 1 year
    • Standard polysomnography. time of sleep periods (Stage 1,2,3,4 and REM) in minutes.
  • Change in Arousal Index
    • Time Frame: 1 year
    • Standard polysomnography, number of arousals per sleep hour
  • Change in Apnea-Hypopnea index
    • Time Frame: 1 year
    • Standard polysomnography, number of apneas and hypoapneas per sleep hour
  • Change in Oxygen desaturation index
    • Time Frame: 1 year
    • Standard polysomnography, number of 3% or more Oxygen desaturations per sleep hour
  • Change in Sleep time with Oxygen saturation below 90%
    • Time Frame: 1 year
    • Standard polysomnography, percentage of sleep time with oxygen saturation below 90%
  • Change in polysomnographic parameters: Total Sleep time (TTS)
    • Time Frame: 1 year
    • Standard polysomnography, time in minutes
  • Change in the blood pressure monitoring
    • Time Frame: at baseline and after a year
    • The blood pressure will be monitored during 24 hours with a Blood Pressure Monitoring device before (baseline) and after intervention (1 year) in both arms measured in mmHg. Change in the mean blood pressure will be compared between arms
  • Incidental cardiovascular events
    • Time Frame: 1 year
    • New hypertension diagnosis or anti-hypertensive treatment, atrial fibrillation, hospitalization for nonfatal myocardial infarction or instable angina, nonfatal stroke or transient ischemic attack or for heart failure episode, and cardiovascular death. Data obtained from official electronic health care databases
  • Health care resources utilization: Hospital admission
    • Time Frame: 1 year
    • Hospital admission measured in number of events
  • Health care resources utilization: Hospital duration
    • Time Frame: 1 year
    • Hospital duration measured in days of hospitalization
  • Health care resources utilization: ICU admission
    • Time Frame: 1 year
    • ICU admission measured in numbers of events
  • Health care resources utilization: ICU duration
    • Time Frame: 1 year
    • ICU duration measured in days of UCI admissions
  • Health care resources utilization: emergency visits
    • Time Frame: 1 year
    • Emergency visits measured in number of events
  • Health care resources utilization: primary care visits
    • Time Frame: 1 year
    • Primary care visits measured in number of events
  • Health care resources utilization: specialist visits
    • Time Frame: 1 year
    • Specialist visits measured in number of events
  • Incidence of new adverse event
    • Time Frame: 1 year
    • Number of adverse events based in CTCAE v4.0
  • Side effects
    • Time Frame: 1 year
    • Incidence or side effects of NIV in follow-up visits: excessive noise, headache, claustrophobia, difficulty in sleep conciliation or maintenance, expiration discomfort.

Participating in This Clinical Trial

Inclusion Criteria

1. Obesity Hypoventilation Syndrome defined by obesity (IMC≥30) and Hypercapnic respiratory failure (PCO 2> 45 mm Hg) in stable phase (PH≥7.35 without clinical signs of worsening in at least one previous month). 2. Age between 18-80 years. 3. Absence of other diseases causing hypercapnia as moderate or severe chronic obstructive pulmonary disease (FEV1> 70% predicted if FEV1 / FVC <70), neuromuscular, thoracic wall or metabolic disease; d) Absence of narcolepsy or restless legs syndrome. 4. Overcome correctly a 30 minutes test of treatment with VNI in wakefulness. Exclusion Criteria:

1. Psychophysical disability for questionnaires. 2. Patients who cannot be evaluated by quality of life questionnaires because they present debilitating chronic disease. 3. Chronic nasal obstruction that prevents the use of NIV. 4. Pregnancy. 5. No informed consent obtained.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sociedad Española de Neumología y Cirugía Torácica
  • Provider of Information About this Clinical Study
    • Principal Investigator: Juan F. Masa, Principal Investigator – Sociedad Española de Neumología y Cirugía Torácica
  • Overall Official(s)
    • Juan F Masa, PhD, Principal Investigator, Hospital San Pedro de Alcantara

References

Mokhlesi B, Kryger MH, Grunstein RR. Assessment and management of patients with obesity hypoventilation syndrome. Proc Am Thorac Soc. 2008 Feb 15;5(2):218-25. doi: 10.1513/pats.200708-122MG.

Nowbar S, Burkart KM, Gonzales R, Fedorowicz A, Gozansky WS, Gaudio JC, Taylor MR, Zwillich CW. Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004 Jan 1;116(1):1-7. doi: 10.1016/j.amjmed.2003.08.022.

Berg G, Delaive K, Manfreda J, Walld R, Kryger MH. The use of health-care resources in obesity-hypoventilation syndrome. Chest. 2001 Aug;120(2):377-83. doi: 10.1378/chest.120.2.377.

Lopez-Jimenez MJ, Masa JF, Corral J, Teran J, Ordaz E, Troncoso MF, Gonzalez-Mangado N, Gonzalez M, Lopez-Martinez S, De Lucas P, Marin JM, Marti S, Diaz-Cambriles T, Diaz-de-Atauri J, Chiner E, Aizpuru F, Egea C, Romero A, Benitez JM, Sanchez-Gomez J, Golpe R, Santiago-Recuerda A, Gomez S, Barbe F, Bengoa M; Grupo cooperativo. Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study. Arch Bronconeumol. 2016 Mar;52(3):158-65. doi: 10.1016/j.arbres.2015.10.003. Epub 2015 Dec 4. English, Spanish.

Masa JF, Celli BR, Riesco JA, Hernandez M, Sanchez De Cos J, Disdier C. The obesity hypoventilation syndrome can be treated with noninvasive mechanical ventilation. Chest. 2001 Apr;119(4):1102-7. doi: 10.1378/chest.119.4.1102.

Perez de Llano LA, Golpe R, Ortiz Piquer M, Veres Racamonde A, Vazquez Caruncho M, Caballero Muinelos O, Alvarez Carro C. Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. 2005 Aug;128(2):587-94. doi: 10.1378/chest.128.2.587.

Janssens JP, Derivaz S, Breitenstein E, De Muralt B, Fitting JW, Chevrolet JC, Rochat T. Changing patterns in long-term noninvasive ventilation: a 7-year prospective study in the Geneva Lake area. Chest. 2003 Jan;123(1):67-79. doi: 10.1378/chest.123.1.67.

Masa JF, Corral J, Alonso ML, Ordax E, Troncoso MF, Gonzalez M, Lopez-Martinez S, Marin JM, Marti S, Diaz-Cambriles T, Chiner E, Aizpuru F, Egea C; Spanish Sleep Network. Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome. Pickwick Study. Am J Respir Crit Care Med. 2015 Jul 1;192(1):86-95. doi: 10.1164/rccm.201410-1900OC.

Piper AJ, Wang D, Yee BJ, Barnes DJ, Grunstein RR. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax. 2008 May;63(5):395-401. doi: 10.1136/thx.2007.081315. Epub 2008 Jan 18.

Borel JC, Tamisier R, Gonzalez-Bermejo J, Baguet JP, Monneret D, Arnol N, Roux-Lombard P, Wuyam B, Levy P, Pepin JL. Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized controlled trial. Chest. 2012 Mar;141(3):692-702. doi: 10.1378/chest.10-2531. Epub 2011 Sep 1.

Berry RB, Chediak A, Brown LK, Finder J, Gozal D, Iber C, Kushida CA, Morgenthaler T, Rowley JA, Davidson-Ward SL; NPPV Titration Task Force of the American Academy of Sleep Medicine. Best clinical practices for the sleep center adjustment of noninvasive positive pressure ventilation (NPPV) in stable chronic alveolar hypoventilation syndromes. J Clin Sleep Med. 2010 Oct 15;6(5):491-509.

Gonzalez-Bermejo J, Perrin C, Janssens JP, Pepin JL, Mroue G, Leger P, Langevin B, Rouault S, Rabec C, Rodenstein D; SomnoNIV Group. Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation. Thorax. 2012 Jun;67(6):546-52. doi: 10.1136/thx.2010.142653. Epub 2010 Oct 22.

Johnson KG, Johnson DC. Treatment of sleep-disordered breathing with positive airway pressure devices: technology update. Med Devices (Auckl). 2015 Oct 23;8:425-37. doi: 10.2147/MDER.S70062. eCollection 2015.

Jaye J, Chatwin M, Dayer M, Morrell MJ, Simonds AK. Autotitrating versus standard noninvasive ventilation: a randomised crossover trial. Eur Respir J. 2009 Mar;33(3):566-71. doi: 10.1183/09031936.00065008.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.