Continuous Positive Pressure Versus Bi-level in Overlap Syndrome
Primary Purpose
Overlap Syndrome, Nocturnal Hypoventilation
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Bi-level positive airway pressure with ventilatory support
continuous positive airway pressure without ventilatory support
Sponsored by
About this trial
This is an interventional treatment trial for Overlap Syndrome
Eligibility Criteria
Inclusion Criteria:
- COPD (FEV1/FVC < 70 (post-BD) and history of smoking - 10 PPY)
- FEV1< 80% and COPD symptoms
- AHI ≥ 15 events/hour
Exclusion Criteria:
- Persistent hypercapnic respiratory failure with acidosis (defined as pH <7.30 after bronchodilators)
- Hypoxia requiring long term oxygen therapy
- BMI > 35 kg/m2
- Previously-initiated long term non-invasive positive pressure ventilation
- Other lung disease resulting in respiratory symptoms
- Age <40 years
- Pregnancy
- Malignant comorbidities
- Patients undergoing renal replacement therapy
- Restrictive lung disease causing hypercapnia
- Severe heart failure, unstable angina and severe arrhythmias
- Inability to comply with the protocol
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
CPAP
Bi-level
Arm Description
Oronasal CPAP therapy applied as per current international guidelines
Oronasal Bi-level therapy + supplemental oxygen (if necessary) applied as per current international guidelines
Outcomes
Primary Outcome Measures
diurnal hypercapnia (pCO2 <= 45 mmH2O )
(PaCO2 <= 45 mmH2O )
nocturnal oxygen desaturation correction
Mean nocturnal SpO2 >=90%, with <10% of the total recording time <90% after correction of leaks)
Secondary Outcome Measures
Changes in FEV1
Forced Expiratory Volume (FEV1) in first second (% of predicted) from pre-intervention to follow up
Changes in FVC
Forced vital capacity (FVC) (% of predicted) from pre-intervention to follow up
Changes in RV
Residual volume (RV) (% of predicted) from pre-intervention to follow up
exercise tolerance
Change in the 6 minute walking test from pre-intervention to follow up
Sleepiness evaluation
Epworth sleepiness scale is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
Comparation of patient score from pre-intervention to follow up
acute respiratory exacerbations
Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission
Compliance to PAP
median hours of compliance per night
PAP usage
percentage of days of use per month
Dyspnoea evaluation
The mMRC Dyspnea Scale quantifies disability attributable to breathlessness and is useful for baseline dyspnea characterization in patients with respiratory diseases. The score can range from 0 to 4. The higher the mMRC score the higher the dyspnea.
Comparation of patient score from pre-intervention to follow up
Symptoms of COPD
COPD Assessment test
Apneia/Hiponeia Index
Number of Residual AHI/per hour
nocturnal hypoventilation
∆PtcCO2<10mmHg during night from pre-intervention to follow up
Full Information
NCT ID
NCT03766542
First Posted
February 8, 2017
Last Updated
December 5, 2018
Sponsor
Hospital Sao Joao
Collaborators
Marta Drummond MD PhD, Joao Carlos Winck MD PhD, Mafalda van Zeller MD Phstud
1. Study Identification
Unique Protocol Identification Number
NCT03766542
Brief Title
Continuous Positive Pressure Versus Bi-level in Overlap Syndrome
Official Title
Optimal Positive Airway Pressure in Overlap Syndrome: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2019 (Anticipated)
Primary Completion Date
July 1, 2020 (Anticipated)
Study Completion Date
September 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Sao Joao
Collaborators
Marta Drummond MD PhD, Joao Carlos Winck MD PhD, Mafalda van Zeller MD Phstud
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
Continuous positive airway pressure (CPAP) became the established treatment for overlap syndrome (OS). It has been showed that the survival benefits of CPAP favored hypercapnic patients. When considering hypercapnic stable COPD patients, survival benefits occurred when the use of bi- level ventilation therapy was targeted to significantly reduce hypercapnia.
This highlights the relevance of hypercapnia and hypoventilation correction. Thus, the purpose of this study is to compare the use of CPAP to Bi-level ventilation in hypercapnic OS patients, since the later may correct not only the airway patency but also increase the magnitude of each breath.
Detailed Description
Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) represent two of the most prevalent respiratory disorders in clinical practice and their coexistence is often described has "overlap syndrome" (OS) In patients with COPD, the coexistence of OSA is associated with an increased risk of death from any cause, and hospitalization because of COPD exacerbation. Treatment with continuous positive airway pressure (CPAP) has been showed to be effective and associated with improved survival and decreased hospitalizations. When CPAP became established treatment for overlap syndrome, a multivariate analysis revealed that the hours of CPAP use were an independent predictor of mortality. Furthermore, it has been showed that the survival benefit of CPAP favors hypercapnic patients with overlap syndrome.
Regarding hypercapnic stable COPD patients, the best results with long-term non-invasive positive pressure ventilation have been noted in studies using more intensive strategies of ventilation, with higher inspiratory pressures and higher backup rates that improved or even normalized daytime hypercapnia. In fact, survival benefits occurred when ventilation was targeted to significantly reduce hypercapnia.
As for typical COPD, overlap syndrome patients might also benefit from optimal daytime hypercapnia correction, which could be better achieved using bi-level ventilation instead of CPAP, since it could not only maintain airway patency but also improve alveolar ventilation.
This study aims to compare CPAP therapy to bi-level ventilatory support in overlap syndrome patients, not only for the efficacy to achieve hypercapnia reduction, but also regarding acute disease exacerbations, symptoms and treatment compliance. Therefore, the authors designed a randomized controlled trial with recruitment and power calculations based on the applicant's own data.
After the diagnosis, patients will be randomized either for CPAP or BPAP treatment.
If CPAP is to be initiated, optimal pressure to maintain upper airway patency will be determined. If there are continued obstructive respiratory events at 15 cm H2O of CPAP, patients will cross-over to the BPAP study arm.
Regarding BPAP titration, patients will be treated with ventilators set in pressure support spontaneous/timed mode, both inspiratory and expiratory positive airway pressures (IPAP and EPAP) will be manually titrated. EPAP will ensure optimal pressure for maintaining upper airway patency and IPAP will be defined according to patient tolerance and pressure support necessary to achieve normal PaCO2 values or to reduce baseline PaCO2 by 20% or more; Follow-up will be performed at 1, 6 and 12 months. Follow-up will include clinical evaluation with physical examination and questionnaires (COPD Assessment test, Epworth Sleepiness Scale and MRC dyspnea score), blood gas analysis, treatment adherence, AHI, nocturnal pulse oximetry and exacerbations.
12-month follow-up will also include lung function test, 6-min walking test and nocturnal capnography.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overlap Syndrome, Nocturnal Hypoventilation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized controlled trial.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CPAP
Arm Type
Active Comparator
Arm Description
Oronasal CPAP therapy applied as per current international guidelines
Arm Title
Bi-level
Arm Type
Experimental
Arm Description
Oronasal Bi-level therapy + supplemental oxygen (if necessary) applied as per current international guidelines
Intervention Type
Device
Intervention Name(s)
Bi-level positive airway pressure with ventilatory support
Intervention Description
Positive airway pressure will be applied in the experimental group through a oronasal interface, in ventilatory support mode (Bi-level) with a fixed backup rate.
Intervention Type
Device
Intervention Name(s)
continuous positive airway pressure without ventilatory support
Intervention Description
Continuous positive airway pressure (CPAP) will be applied in the active comparator group through a oronasal interface.
Primary Outcome Measure Information:
Title
diurnal hypercapnia (pCO2 <= 45 mmH2O )
Description
(PaCO2 <= 45 mmH2O )
Time Frame
1 year
Title
nocturnal oxygen desaturation correction
Description
Mean nocturnal SpO2 >=90%, with <10% of the total recording time <90% after correction of leaks)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Changes in FEV1
Description
Forced Expiratory Volume (FEV1) in first second (% of predicted) from pre-intervention to follow up
Time Frame
1 year
Title
Changes in FVC
Description
Forced vital capacity (FVC) (% of predicted) from pre-intervention to follow up
Time Frame
1 year
Title
Changes in RV
Description
Residual volume (RV) (% of predicted) from pre-intervention to follow up
Time Frame
1 year
Title
exercise tolerance
Description
Change in the 6 minute walking test from pre-intervention to follow up
Time Frame
1 year
Title
Sleepiness evaluation
Description
Epworth sleepiness scale is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
Comparation of patient score from pre-intervention to follow up
Time Frame
1 year
Title
acute respiratory exacerbations
Description
Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission
Time Frame
1 year
Title
Compliance to PAP
Description
median hours of compliance per night
Time Frame
1 year
Title
PAP usage
Description
percentage of days of use per month
Time Frame
1 year
Title
Dyspnoea evaluation
Description
The mMRC Dyspnea Scale quantifies disability attributable to breathlessness and is useful for baseline dyspnea characterization in patients with respiratory diseases. The score can range from 0 to 4. The higher the mMRC score the higher the dyspnea.
Comparation of patient score from pre-intervention to follow up
Time Frame
1 year
Title
Symptoms of COPD
Description
COPD Assessment test
Time Frame
1 year
Title
Apneia/Hiponeia Index
Description
Number of Residual AHI/per hour
Time Frame
1 year
Title
nocturnal hypoventilation
Description
∆PtcCO2<10mmHg during night from pre-intervention to follow up
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
COPD (FEV1/FVC < 70 (post-BD) and history of smoking - 10 PPY)
FEV1< 80% and COPD symptoms
AHI ≥ 15 events/hour
Exclusion Criteria:
Persistent hypercapnic respiratory failure with acidosis (defined as pH <7.30 after bronchodilators)
Hypoxia requiring long term oxygen therapy
BMI > 35 kg/m2
Previously-initiated long term non-invasive positive pressure ventilation
Other lung disease resulting in respiratory symptoms
Age <40 years
Pregnancy
Malignant comorbidities
Patients undergoing renal replacement therapy
Restrictive lung disease causing hypercapnia
Severe heart failure, unstable angina and severe arrhythmias
Inability to comply with the protocol
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Continuous Positive Pressure Versus Bi-level in Overlap Syndrome
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