Clinical trial NCT03766542: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Overlap Syndrome
Nocturnal Hypoventilation
Lead sponsor: Hospital Sao Joao
Sponsor class: OTHER
Collaborators: name: Marta Drummond MD PhD
name: Joao Carlos Winck MD PhD
name: Mafalda van Zeller MD Phstud
First posted: 2018-12-06
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized controlled trial.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: diurnal hypercapnia (pCO2 <= 45 mmH2O )
timeFrame: 1 year
measure: nocturnal oxygen desaturation correction
timeFrame: 1 year
Secondary outcomes:
measure: Changes in FEV1
timeFrame: 1 year
measure: Changes in FVC
timeFrame: 1 year
measure: Changes in RV
timeFrame: 1 year
measure: exercise tolerance
timeFrame: 1 year
measure: Sleepiness evaluation
timeFrame: 1 year
measure: acute respiratory exacerbations
timeFrame: 1 year
measure: Compliance to PAP
timeFrame: 1 year
measure: PAP usage
timeFrame: 1 year
measure: Dyspnoea evaluation
timeFrame: 1 year
measure: Symptoms of COPD
timeFrame: 1 year
measure: Apneia/Hiponeia Index
timeFrame: 1 year
measure: nocturnal hypoventilation
timeFrame: 1 year
Other outcomes:
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