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Non-invasive Ventilation Versus Sham Ventilation in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Collaborators:
Philips Respironics
The Hong Kong Lung Foundation
Information provided by:
United Christian Hospital
ClinicalTrials.gov Identifier:
NCT00429156
First received: January 30, 2007
Last updated: October 22, 2009
Last verified: October 2009

January 30, 2007
October 22, 2009
January 2007
February 2009   (final data collection date for primary outcome measure)
Time to first life-threatening event (recurrent AHRF and death) within the first year of hospital discharge, after an episode of AHRF treated by acute NIV. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Time to first life-threatening event (recurrent AHRF and death) within the first year of hospital discharge, after an episode of AHRF treated by acute NIV.
Complete list of historical versions of study NCT00429156 on ClinicalTrials.gov Archive Site
  • Withdrawal from study [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Number of readmissions [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • NIV use [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Intubation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Hospitalised days [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Blood gases levels in the first year after discharge [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Withdrawal from study, number of readmissions, NIV use, intubation, hospitalised days, blood gases levels in the first year after discharge.
Not Provided
Not Provided
 
Non-invasive Ventilation Versus Sham Ventilation in Chronic Obstructive Pulmonary Disease (COPD)
A Randomised Controlled Trial of Continuation of Home Non-invasive Ventilation vs Sham Ventilation in Survivors of Acute Hypercapnic Respiratory Failure in Chronic Obstructive Pulmonary Disease

The investigators hypothesize that continuation of non-invasive ventilation (NIV) at home after an episode of acute hypercapnic respiratory failure (AHRF) treated by NIV in COPD patients would reduce the likelihood of death and recurrent AHRF requiring NIV or intubation. The investigators designed this study in a way that recruited COPD patients would be started on home NIV or sham treatment after an episode of AHRF requiring acute NIV. The patients are acclimatised to NIV application after a few days of acute use. The investigators chose occurrence of life-threatening event (recurrent AHRF and death) as the primary endpoint.

Non-invasive ventilation (NIV) has been shown in randomised controlled trials to improve arterial blood gases, reduce intubation and mortality rates in patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD) complicated by acute hypercapnic respiratory failure (AHRF) [1-7]. Despite success of NIV in AHRF of COPD, survivors of this group of patients might suffer from further episodes of AHRF after discharge. It has been found in a recent study that COPD patients who survived AHRF after treatment with acute NIV had a high risk of readmission and life-threatening events in the ensuing year [8]. At one year after discharge, 80% had been readmitted for respiratory diagnoses, 63% had another life-threatening event and 49% had died, mainly due to respiratory failure. Survivors spent a median of 12% time hospitalized in the subsequent year. A significant proportion of survivors required repeated NIV for recurrent AHRF. Another study showed that in COPD patients who declined intubation for AHRF and were treated with acute NIV, these outcomes were even worse, with a 1-year survival of only 30% [9]. It becomes imperative to find ways to reduce the occurrence of life-threatening events in the survivors.

There has been uncontrolled data to suggest that home NIV might reduce both hospital admissions and clinic visits in severe COPD with hypercapnic respiratory failure. In 11 severe stable COPD patients with chronic hypercapnia who did not respond to conventional treatment, Jones et al put them on home NIV [10]. Hospital admissions and clinic visits were halved in the subsequent year, together with a sustained improvement in arterial blood gases. Cost saving was demonstrated with home NIV in severe COPD in another study [11]. However, results from randomized controlled studies (RCTs) are conflicting. Three early studies suggested that home NIV was not superior to standard treatment in stable severe COPD [12, 13, 14]. On the other hand, Meecham-Jones et al found that NIV with long term oxygen therapy (LTOT) significantly improved daytime blood gases, nocturnal gas exchange and sleep quality in severe COPD [15]. A long-term RCT on home NIV in severe COPD showed that home NIV significantly reduced dyspnoea ratings, improved psychomotor coordination and decreased hospital admissions at 3 month, though reduction in hospital admissions was no longer evident by 12 months [16]. However, these randomized studies have been criticized for including chronic stable COPD patients who were not hypercapnic enough to benefit from home NIV, using inadequate inflation pressures, inadequate patient acclimatization time and not selecting the optimal outcome variables [17]. In the most recent RCT [18], home NIV with LTOT was shown to significantly improve gas exchange, dyspnoea score and quality of life; there was also a trend to reduced hospital and ICU admissions. However, the study was only powered to detect improvement in daytime PaCO2 in the NIV group.

We hypothesize that continuation of NIV at home after an episode of AHRF treated by NIV in COPD patients would reduce the likelihood of death and recurrent AHRF requiring NIV or intubation. We design this study in a way that recruited COPD patients would be started on home NIV or sham treatment after an episode of AHRF requiring acute NIV. The patients are acclimatised to NIV application after a few days of acute use. We choose occurrence of life-threatening event (recurrent AHRF and death) as the primary endpoint.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hypercapnic Respiratory Failure
  • Chronic Obstructive Pulmonary Disease
  • Device: Home non-invasive ventilation
    Continuation of home non-invasive ventilation after acute NIV for AHRF in COPD. Daily nocturnal treatment by home NIV for 1 year.
    Other Name: BiPAP Synchrony® (Respironics Inc., Murrysville, PA)
  • Device: Home non-invasive ventilation (sham)
    Continuation of home non-invasive ventilation after acute NIV for AHRF in COPD. Daily nocturnal treatment by home sham NIV (CPAP 5 cm H2O) for 1 year.
    Other Name: BiPAP Synchrony® (Respironics Inc., Murrysville, PA)
  • Active Comparator: 1
    Home non-invasive ventilation
    Intervention: Device: Home non-invasive ventilation
  • Sham Comparator: 2
    Home sham non-invasive ventilation with CPAP 5 cm H2O
    Intervention: Device: Home non-invasive ventilation (sham)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
February 2009
February 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • COPD patient with AHRF who survives after treatment with NIV and successfully weaned off for at least 48 hours.
  • Patients who have been intubated and mechanically ventilated can be included if they have also been treated with NIV in the same hospital admission
  • Significant obstructive sleep apnoea ruled out by overnight polysomnography done after successful weaning of NIV (Apnoea-hypopnoea index, AHI, < 10/hr
  • Patients willing to give their written informed consent to participate in the study
  • Patients understand that he/she would be randomised into receiving home NIV or sham ventilation
  • Patients who are able to use the home pressure support ventilators after a period of acclimatisation and training before discharge from the hospital

Exclusion Criteria:

  • Patients with non-COPD causes of AHRF (e.g. asthma, bronchiectasis or lobar pneumonia, fibrothorax, acute pulmonary oedema, etc)
  • Patients who have contraindications to NIV and those who refused or failed NIV during an initial 15-minute acclimatization period
  • Active smoker
  • An increase of ≥ 15% in FEV1 after inhaled salbutamol (200μg)
  • Obstructive sleep apnoea (OSA) with apnoea-hypopnoea index (AHI) of ≥ 10/hr
  • Other significant co-morbid conditions that in the investigators' view, would confer an adverse prognosis during the study period, e.g., congestive heart failure, uncontrolled diabetes mellitus, tuberculosis, neoplasms, peripheral vascular disease threatening organ functions
  • Adverse psycho-social circumstances not conducive to home NIV treatment (Appendix 2)
  • On long-term systemic steroid (prednisolone ≥ 7.5 mg per day for ≥ 3 months)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Hong Kong
 
NCT00429156
KC/KE 06-0147/FR-1
Yes
Dr C M Chu, United Christian Hospital
United Christian Hospital
  • Philips Respironics
  • The Hong Kong Lung Foundation
Principal Investigator: Chung-Ming Chu, MD United Christian Hospital
United Christian Hospital
October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP