Exacerbation Prevention GOLD IV COPD With Non Invasive Mechanical Ventilation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of high-intensity non invasive mechanical ventilation (during one year to reduce the severity and frequency of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in patients with frequent AECOPD (frequent exacerbations defined more two or more AECOPD) and in GOLD IV stage (very severe COPD). The design is a randomised, double blind and controled with placebo (sham maneuver) clinical trial.

Detailed Description
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Background: There are many previous studies (no controlled trials or observational studies)that demonstrated minimal benefits (on gas exchange and marginal effect over exacerbations frequency) with the use of non invasive mechanical ventilation, in BiPAP modality with IPAP pressures <18H2ocm (low intensity), in COPD patients. In subsequent years there were controled trials that concluded that there was no benefits with the use of non invasive mechanical ventilation on BiPAP mode in COPD patients ( It should be mentioned that in most trials were used low inspiratory pressure levels, that is called low-intensity non invasive mechanical ventilation). However, there are other recent studies that described some benefits of high intensity Bilevel modality of non invasive mechanical ventilation (inspiratory pressures >18cmH2O) specially on gas exchange, quality of life and functional status. There are some issues that do not yet have a clear answer like the optimal inspiratory pressure (IPAP) or the ventilation modality (BIPAP or other) to obtain the maximal benefit on COPD patients. Additionally, is not clear also if the use of non invasive mechanical ventilation on COPD patients helps to reduce the frequency and severity of acute exacerbations of COPD (AECOPD). This study have some characteristics that are different to the previous reports: The inclusion of patients with frequent exacerbations phenotype (and therefore worst prognosis patients)that there are no included in previous trials The intervention maneuver that is bilevel modality of non invasive mechanical ventilation at hig-intensity pressure (>18H2Ocm and <24H2Ocm) The use of placebo maneuver (CPAP Sham) The home titration in three phases, over a week The long-term use of the intervention and sham maneuver

Official Title
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Exacerbation's Prevention in Patients With COPD in GOLD IV Stage (Very Severe) With Non Invasive Mechanical Ventilation

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Device: BiPAP Pro 2, Phillips Respironics
* Device: CPAP sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and spirometric diagnosis for COPD (FEV1/FVC <70%) Clinical phenotype of frequent exacerbations Must sign the informed consent Former smokers Stable COPD FEV1 <35% Optimal medical treatment Exclusion Criteria: OSAS diagnosis Other indications for non invasive mechanical ventilation Arterial pressure for dioxide carbon >45mmHg Lung cancer Impossibility for doing spirometry or going to the medical visits Be included in another study

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: cpap sham<br>non invasive mechanical ventilation type cpap sham manoeuver | Device: BiPAP Pro 2, Phillips Respironics<br>* mechanical ventilation type bilevel at high intensity (>18mmHg) for at least six hours, nocturnal ventilation.<br>* Other names: high intensity bilevel;Device: CPAP sham<br>* CPAP sham maneuver (IPAP less or equal to 4cmH2O)<br>* Other names: sham non invasive ventilation;|
| Active Comparator: high-intensity NIMV<br>Non-invasive mechanical ventilation, biPAP modality, with high-intensity IPAP (>18cmH2O) | Device: BiPAP Pro 2, Phillips Respironics<br>* mechanical ventilation type bilevel at high intensity (>18mmHg) for at least six hours, nocturnal ventilation.<br>* Other names: high intensity bilevel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute exacerbations of Chronic Obstructive Pulmonary Disease frequency | It will be calculated the exacerbation/year-patien rate and will be compared between groups | 1 year | 
| acute exacerbation of chronic obstructive pulmonary disease severity | It will be measured the rate of AECOPD with hospitalary and Intensive Care Unity requirement | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lymphocyte subpopulations Th-1 and Th-17 | It will be measured the lymphocyte subpopulations like Th-1 and Th-17 | 1 year | 
| six-minute walking test |  | 1 year | 
| Forced expiratory volume in first second (FEV1) and forced expiratory capacity |  | 1 year | 
| Maximal inspiratory pressure and maximal expiratory pressure |  | 1 año | 
| gas exchange response (carbon and oxygen dioxide arterial pressure) |  | 1 year | 
| Health related quality of life |  | one year | 
| anxiety and depression measures (HAD and Beck Questionnaires) |  | one year | 
| echocardiographic parameters |  | one year | 
| survival |  | one year | 
| IL-1 and IL-6 cytokines | it will be measured the level of interleukines 1 and 6(IL-1 and IL-6) | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute exacerbation of COPD number, acute exacerbation of COPD severity