Clinical trial NCT00135538: The Additional Value of Noninvasive Ventilation Next to Rehabilitation in Hypercapnic COPD Patients
Official title: Does Chronic Ventilatory Support Improve the Outcomes of Rehabilitation in Hypercapnic COPD Patients?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Pulmonary Disease, Chronic Obstructive
Intermittent Positive-Pressure Ventilation
Rehabilitation
Lead sponsor: Groningen Research Institute for Asthma and COPD
Sponsor class: OTHER
Collaborators: name: The Netherlands Asthma Foundation
First posted: 2005-08-26
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate whether noninvasive ventilation by nose mask during the night has additional benefits next to pulmonary rehabilitation in patients with severe hypercapnic COPD.

Detailed description: Several randomised controlled trials in patients with stable Chronic Obstructive Pulmonary Disease (COPD) have demonstrated that pulmonary rehabilitation (PR) improves dyspnoea, exercise tolerance, and health-related quality of life. Research in this field has been important in our department for several years. The first study in this respect was started in 1986 comparing outpatient rehabilitation with rehabilitation in the community in patients with severe COPD. This study showed that rehabilitation supervised by a physical therapist in the community is effective for a long period in contrast to outpatient rehabilitation. In 1990 the second study started showing that positive initial benefits of home based rehabilitation on quality of life can be maintained for 18 months if the patients visit the local physical therapist once a month.

However, less positive effects of rehabilitation have been reported in the more severe patients. Because of dyspnoea due to inspiratory muscle fatigue patients may not receive an adequate training stimulus, and therefore rehabilitation might be less effective. In these more severe patients alternative therapies are needed. These non-pharmacological treatments include nutritional supplementation, oxygen therapy, lung transplantation, lung volume reduction surgery and ventilatory support.

The last few years a discussion within the 4 home mechanical ventilation centres (HMV) in the Netherlands has been started about the role of chronic ventilatory support in end-stage COPD. Theoretically, it might be effective because:

1. a resetting of the respiratory centre may reduce daytime PaCO2;
2. a better internal milieu (pH, PaO2, PaCO2) may improve peripheral muscle function;
3. resting the respiratory muscles during the night may increase their daytime strength and endurance;
4. a reduction in the number of nocturnal arousals may improve the quality of sleep. Nevertheless, none of these mechanisms has been proven and currently there is no evidence that noninvasive positive pressure ventilation (NIPPV) should be given to stable patients with COPD. While several randomised controlled trials (RCT's) on NIPPV have been published with different outcomes, a recent meta-analysis did not show beneficial effects on blood gasses, lung function, respiratory muscle function and walking distance.

In contrast several uncontrolled studies did show clear benefits from NIPPV on gas-exchange, dyspnoea and quality of life. Possible reasons for these conflicting outcomes are differences in:

1. selection of patients,
2. adequacy of ventilatory support,
3. length of ventilatory support. Interestingly, it seems that studies with a positive outcome included mainly patients with hypercapnia, suggesting this as an important selection criterion.

The hypothesis is that long term NIPPV in hypercapnic patients with COPD may improve the effects of rehabilitation at home regarding health status, ADL function, dyspnoea and exercise tolerance. Secondly, we like to elucidate the exact mechanisms why NIPPV might be effective in this group of patients.

Comparison: patients who receive noninvasive ventilation during the night while following a pulmonary rehabilitation program with patients who only follow a rehabilitation program without receiving the noninvasive ventilation.

Eligibility criteria: Inclusion Criteria:

* COPD (FEV1\< 50%, Tiffeneau \< 70%)
* Dyspnoea on exertion and a reduced exercise capacity
* Age 75 years or less
* PaCO2 \> 6.0 kPa at rest without oxygen

Exclusion Criteria:

* Cardial/neuromuscular diseases limiting a successful rehabilitation
* Obstructive sleep apnoea syndrome: apnea/hypopnea index (AHI) \> 10
* Previous exposure to chronic NIPPV
* Participation in a pulmonary rehabilitation program less than 18 months ago

Primary outcomes:
measure: Health related quality of life measured by the Chronic Respiratory Questionnaire
Secondary outcomes:
measure: Activities of daily Living
measure: Dyspnea (Medical Research Council Scale [MRC], baseline dyspnea index [BDI], Borg)
measure: Exercise tolerance (Cycle ergometer test, 6-minute walk distance [6-MWD], incremental shuttle walking test [ISWT], endurance shuttle walking test [ESWT])
measure: Pulmonary function testing
measure: Sleep quality (polysomnography)
measure: Respiratory muscle activity (endurance shuttle walking test [EMG])
measure: Respiratory muscle strength (PImax, PEmax)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University medical Hospital Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Marieke L Duiverman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Altenburg WA, Duiverman ML, Ten Hacken NH, Kerstjens HA, de Greef MH, Wijkstra PJ, Wempe JB. Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method. Respir Res. 2015 Feb 19;16(1):27. doi: 10.1186/s12931-015-0182-x.
citation: Duiverman ML, Wempe JB, Bladder G, Vonk JM, Zijlstra JG, Kerstjens HA, Wijkstra PJ. Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: a randomized controlled trial. Respir Res. 2011 Aug 23;12(1):112. doi: 10.1186/1465-9921-12-112.
citation: Duiverman ML, Wempe JB, Bladder G, Jansen DF, Kerstjens HA, Zijlstra JG, Wijkstra PJ. Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD. Thorax. 2008 Dec;63(12):1052-7. doi: 10.1136/thx.2008.099044. Epub 2008 Aug 18.
citation: Duiverman ML, Wempe JB, Bladder G, Kerstjens HA, Wijkstra PJ. Health-related quality of life in COPD patients with chronic respiratory failure. Eur Respir J. 2008 Aug;32(2):379-86. doi: 10.1183/09031936.00163607. Epub 2008 Apr 2.