Clinical trial NCT01481727: Exacerbation Prevention GOLD IV COPD With Non Invasive Mechanical Ventilation
Official title: Exacerbation's Prevention in Patients With COPD in GOLD IV Stage (Very Severe) With Non Invasive Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: acute exacerbation of COPD number
acute exacerbation of COPD severity
Lead sponsor: National Institute of Respiratory Diseases, Mexico
Sponsor class: OTHER_GOV
First posted: 2011-11-29
Enrollment: 20
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: acute exacerbations of Chronic Obstructive Pulmonary Disease frequency
timeFrame: 1 year
measure: acute exacerbation of chronic obstructive pulmonary disease severity
timeFrame: 1 year
Secondary outcomes:
measure: lymphocyte subpopulations Th-1 and Th-17
timeFrame: 1 year
measure: six-minute walking test
timeFrame: 1 year
measure: Forced expiratory volume in first second (FEV1) and forced expiratory capacity
timeFrame: 1 year
measure: Maximal inspiratory pressure and maximal expiratory pressure
timeFrame: 1 año
measure: gas exchange response (carbon and oxygen dioxide arterial pressure)
timeFrame: 1 year
measure: Health related quality of life
timeFrame: one year
measure: anxiety and depression measures (HAD and Beck Questionnaires)
timeFrame: one year
measure: echocardiographic parameters
timeFrame: one year
measure: survival
timeFrame: one year
measure: IL-1 and IL-6 cytokines
timeFrame: one year
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: National Institute of Respiratory Diseases
Study officials:
affiliation: NATIONAL INSTITUTE OF RESPIRATORY DISEASES
name: RAUL HUMBERTO SANSORES MARTINEZ, MMS and MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McEvoy RD, Pierce RJ, Hillman D, Esterman A, Ellis EE, Catcheside PG, O'Donoghue FJ, Barnes DJ, Grunstein RR; Australian trial of non-invasive Ventilation in Chronic Airflow Limitation (AVCAL) Study Group. Nocturnal non-invasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Thorax. 2009 Jul;64(7):561-6. doi: 10.1136/thx.2008.108274. Epub 2009 Feb 12.
citation: Clini E, Sturani C, Rossi A, Viaggi S, Corrado A, Donner CF, Ambrosino N; Rehabilitation and Chronic Care Study Group, Italian Association of Hospital Pulmonologists (AIPO). The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients. Eur Respir J. 2002 Sep;20(3):529-38. doi: 10.1183/09031936.02.02162001.
citation: Casanova C, Celli BR, Tost L, Soriano E, Abreu J, Velasco V, Santolaria F. Long-term controlled trial of nocturnal nasal positive pressure ventilation in patients with severe COPD. Chest. 2000 Dec;118(6):1582-90. doi: 10.1378/chest.118.6.1582.
citation: Lin CC. Comparison between nocturnal nasal positive pressure ventilation combined with oxygen therapy and oxygen monotherapy in patients with severe COPD. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):353-8. doi: 10.1164/ajrccm.154.2.8756806.
citation: Windisch W, Haenel M, Storre JH, Dreher M. High-intensity non-invasive positive pressure ventilation for stable hypercapnic COPD. Int J Med Sci. 2009;6(2):72-6. doi: 10.7150/ijms.6.72. Epub 2009 Feb 27.
citation: Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax. 2010 Apr;65(4):303-8. doi: 10.1136/thx.2009.124263.
citation: Windisch W, Kostic S, Dreher M, Virchow JC Jr, Sorichter S. Outcome of patients with stable COPD receiving controlled noninvasive positive pressure ventilation aimed at a maximal reduction of Pa(CO2). Chest. 2005 Aug;128(2):657-62. doi: 10.1378/chest.128.2.657.
citation: Budweiser S, Hitzl AP, Jorres RA, Heinemann F, Arzt M, Schroll S, Pfeifer M. Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study. Int J Clin Pract. 2007 Sep;61(9):1516-22. doi: 10.1111/j.1742-1241.2007.01427.x.