Back to resultsRandomized Controlled Trial Between Auto-titration and Manual Titration of Non-invasive Ventilation in Obesity Hypoventilation Syndrome (TITRATION)
Primary Purpose
Chronic Hypercapnic Respiratory Failure, Obesity Hypoventilation Syndrome
Status
Active
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Manual Non invasive ventilation titration
Automatic Non invasive ventilation titration
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hypercapnic Respiratory Failure focused on measuring Chronic respiratory failure, Obesity, Non invasive mechanical ventilation
Eligibility Criteria
Inclusion Criteria:
- 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).
- Age between 18-80 years.
- 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.
- Overcome correctly a 30 minutes test of treatment with VNI in wakefulness.
Exclusion Criteria:
- Psychophysical disability for questionnaires.
- Patients who cannot be evaluated by quality of life questionnaires because they present debilitating chronic disease.
- Chronic nasal obstruction that prevents the use of NIV.
- Pregnancy.
- No informed consent obtained.
Sites / Locations
- Juan F. Masa
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Manual
Automatic
Arm Description
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.
In this group the ventilator will run in an automatic mode (AVAPS) with the same Phillips A40 ventilator.
Outcomes
Primary Outcome Measures
Change in PaCO2 between arms
Arterial blood gases while room air breathing expressed in mmHg
Secondary Outcome Measures
Cost-effectiveness analysis by primary outcome
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
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
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)
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)
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.
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
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
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
Arterial blood gases while breathing room air expressed in mmol/L
Change in PaO2
Arterial blood gases while breathing room air expressed PaO2 in mmHg
Change in pH
Arterial blood gases while breathing room air
Change in polysomnographic Sleep periods
Standard polysomnography. time of sleep periods (Stage 1,2,3,4 and REM) in minutes.
Change in Arousal Index
Standard polysomnography, number of arousals per sleep hour
Change in Apnea-Hypopnea index
Standard polysomnography, number of apneas and hypoapneas per sleep hour
Change in Oxygen desaturation index
Standard polysomnography, number of 3% or more Oxygen desaturations per sleep hour
Change in Sleep time with Oxygen saturation below 90%
Standard polysomnography, percentage of sleep time with oxygen saturation below 90%
Change in polysomnographic parameters: Total Sleep time (TTS)
Standard polysomnography, time in minutes
Change in the blood pressure monitoring
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
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
Hospital admission measured in number of events
Health care resources utilization: Hospital duration
Hospital duration measured in days of hospitalization
Health care resources utilization: ICU admission
ICU admission measured in numbers of events
Health care resources utilization: ICU duration
ICU duration measured in days of UCI admissions
Health care resources utilization: emergency visits
Emergency visits measured in number of events
Health care resources utilization: primary care visits
Primary care visits measured in number of events
Health care resources utilization: specialist visits
Specialist visits measured in number of events
Incidence of new adverse event
Number of adverse events based in CTCAE v4.0
Side effects
Incidence or side effects of NIV in follow-up visits: excessive noise, headache, claustrophobia, difficulty in sleep conciliation or maintenance, expiration discomfort.
Full Information
NCT ID
NCT04327336
First Posted
May 15, 2018
Last Updated
April 11, 2023
Sponsor
Sociedad Española de Neumología y Cirugía Torácica
1. Study Identification
Unique Protocol Identification Number
NCT04327336
Brief Title
Randomized Controlled Trial Between Auto-titration and Manual Titration of Non-invasive Ventilation in Obesity Hypoventilation Syndrome
Acronym
TITRATION
Official Title
Effectiveness of Noninvasive Ventilation Adjusted Automatically in the Obesity Hypoventilation Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1, 2020 (Actual)
Primary Completion Date
July 1, 2023 (Anticipated)
Study Completion Date
October 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sociedad Española de Neumología y Cirugía Torácica
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hypercapnic Respiratory Failure, Obesity Hypoventilation Syndrome
Keywords
Chronic respiratory failure, Obesity, Non invasive mechanical ventilation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective, Randomized, double arm, double blind controlled trial.
Masking
ParticipantInvestigator
Masking Description
Two investigators (named Investigator 1 and Investigator 2) participate in each center, with different tasks. Investigator 1 is responsible of randomization and will be aware of the study group assigned to the patient. Investigator 2 will collect in each visit health resource utilization, specific and QoL tests and laboratory test results. Investigator 2 does not know the study arm.
Patients will not be informed about the ventilator settings and the menu of the ventilator will be locked, so they cannot access to ventilator data.
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Manual
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Automatic
Arm Type
Active Comparator
Arm Description
In this group the ventilator will run in an automatic mode (AVAPS) with the same Phillips A40 ventilator.
Intervention Type
Device
Intervention Name(s)
Manual Non invasive ventilation titration
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Automatic Non invasive ventilation titration
Intervention Description
Automatic Group: the A40 ventilator in the automatic AVAPS mode will be adjusted in order to achieve 8-10 ml/kg of ideal weight.
Primary Outcome Measure Information:
Title
Change in PaCO2 between arms
Description
Arterial blood gases while room air breathing expressed in mmHg
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Cost-effectiveness analysis by primary outcome
Description
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.
Time Frame
1 year
Title
Cost-effectiveness analysis by QALY
Description
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.
Time Frame
1 year
Title
Change in subjective daytime sleepiness
Description
Sleepiness evaluated by Epworth sleepiness scale, range from 0 to 24, being 0 the best result and 24 the worst.
Time Frame
1 year
Title
Change in Quality of life measured by Functional Sleep Outcomes of Sleep Questionnaire (FOSQ)
Description
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 .
Time Frame
1 year
Title
Change in Quality of life measured by visual analogical wellbeing scale (VAWS)
Description
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 .
Time Frame
1 year
Title
Change in Quality of life measured by Euroqol 5D.
Description
Quality of life measured by Euroqol 5D, range from 0 to 1, being 0 the worst result and 1 the best result .
Time Frame
1 year
Title
Change in Quality of life measured by Short Form-36 (SF36), Mental component
Description
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.
Time Frame
1 year
Title
Change in Quality of life measured by Short Form-36 (SF36), Physical component
Description
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.
Time Frame
1 year
Title
Change in Bicarbonate arterial blood concentration
Description
Arterial blood gases while breathing room air expressed in mmol/L
Time Frame
1 year
Title
Change in PaO2
Description
Arterial blood gases while breathing room air expressed PaO2 in mmHg
Time Frame
1 year
Title
Change in pH
Description
Arterial blood gases while breathing room air
Time Frame
1 year
Title
Change in polysomnographic Sleep periods
Description
Standard polysomnography. time of sleep periods (Stage 1,2,3,4 and REM) in minutes.
Time Frame
1 year
Title
Change in Arousal Index
Description
Standard polysomnography, number of arousals per sleep hour
Time Frame
1 year
Title
Change in Apnea-Hypopnea index
Description
Standard polysomnography, number of apneas and hypoapneas per sleep hour
Time Frame
1 year
Title
Change in Oxygen desaturation index
Description
Standard polysomnography, number of 3% or more Oxygen desaturations per sleep hour
Time Frame
1 year
Title
Change in Sleep time with Oxygen saturation below 90%
Description
Standard polysomnography, percentage of sleep time with oxygen saturation below 90%
Time Frame
1 year
Title
Change in polysomnographic parameters: Total Sleep time (TTS)
Description
Standard polysomnography, time in minutes
Time Frame
1 year
Title
Change in the blood pressure monitoring
Description
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
Time Frame
at baseline and after a year
Title
Incidental cardiovascular events
Description
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
Time Frame
1 year
Title
Health care resources utilization: Hospital admission
Description
Hospital admission measured in number of events
Time Frame
1 year
Title
Health care resources utilization: Hospital duration
Description
Hospital duration measured in days of hospitalization
Time Frame
1 year
Title
Health care resources utilization: ICU admission
Description
ICU admission measured in numbers of events
Time Frame
1 year
Title
Health care resources utilization: ICU duration
Description
ICU duration measured in days of UCI admissions
Time Frame
1 year
Title
Health care resources utilization: emergency visits
Description
Emergency visits measured in number of events
Time Frame
1 year
Title
Health care resources utilization: primary care visits
Description
Primary care visits measured in number of events
Time Frame
1 year
Title
Health care resources utilization: specialist visits
Description
Specialist visits measured in number of events
Time Frame
1 year
Title
Incidence of new adverse event
Description
Number of adverse events based in CTCAE v4.0
Time Frame
1 year
Title
Side effects
Description
Incidence or side effects of NIV in follow-up visits: excessive noise, headache, claustrophobia, difficulty in sleep conciliation or maintenance, expiration discomfort.
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Adherent vs. non-adherent to noninvasive ventilation therapy subgroups
Description
Efficacy between arms measuring Epworth sleepiness scale (from 0 to 24 points) comparing adherent vs. non-adherent to non-invasive ventilation therapy subgroups (higher and lower of 4 hours per day)
Time Frame
1 year
Title
Sleep apnea severity subgroup
Description
Efficacy between arms measuring Epworth sleepiness scale (from 0 to 24 points) comparing sleep apnea severity subgroups measured by apnea and hypopnea index at baseline (higher and lower of the median)
Time Frame
1 year
Title
Hypercapnia severity subgroup
Description
Efficacy between arms measuring Epworth sleepiness scale (from 0 to 24 points) comparing hypercapnia severity subgroups measured by PaCO2 (mmHg) at baseline (higher and lower of the median)
Time Frame
1 year
Title
Systemic hypertension subgroup
Description
Efficacy between arms measuring Epworth sleepiness scale (from 0 to 24 points) comparing the presence of hypertension diagnosis subgroups at baseline
Time Frame
1 year
Title
Hypercapnia resolution subgroup
Description
Efficacy between arms measuring Epworth sleepiness scale (from 0 to 24 points) comparing the resolution of hypercapnia measured by PaCO2 (mmHg) at the end of the follow-up (higher and lower of 45 mmHg)
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Age between 18-80 years.
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.
Overcome correctly a 30 minutes test of treatment with VNI in wakefulness.
Exclusion Criteria:
Psychophysical disability for questionnaires.
Patients who cannot be evaluated by quality of life questionnaires because they present debilitating chronic disease.
Chronic nasal obstruction that prevents the use of NIV.
Pregnancy.
No informed consent obtained.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan F Masa, PhD
Organizational Affiliation
Hospital San Pedro de Alcantara
Official's Role
Principal Investigator
Facility Information:
Facility Name
Juan F. Masa
City
Cáceres
ZIP/Postal Code
10003
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18250215
Citation
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.
Results Reference
background
PubMed Identifier
14706658
Citation
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.
Results Reference
background
PubMed Identifier
11502632
Citation
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.
Results Reference
background
PubMed Identifier
26656679
Citation
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.
Results Reference
background
PubMed Identifier
11296176
Citation
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.
Results Reference
background
PubMed Identifier
16100142
Citation
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.
Results Reference
background
PubMed Identifier
12527605
Citation
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.
Results Reference
background
PubMed Identifier
25915102
Citation
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.
Results Reference
background
PubMed Identifier
18203817
Citation
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.
Results Reference
background
PubMed Identifier
21885724
Citation
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.
Results Reference
background
PubMed Identifier
20957853
Citation
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.
Results Reference
background
PubMed Identifier
20971982
Citation
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.
Results Reference
background
PubMed Identifier
26604837
Citation
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.
Results Reference
background
PubMed Identifier
19251798
Citation
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.
Results Reference
background
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Randomized Controlled Trial Between Auto-titration and Manual Titration of Non-invasive Ventilation in Obesity Hypoventilation Syndrome
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