Non-invasive Positive Pressure Ventilation for the Treatment of Severe Stable Chronic Obstructive Pulmonary Disease: A Prospective, Multicentre, Randomised, Controlled Clinical Trial

Lancet Respir Med. 2014 Sep;2(9):698-705. doi: 10.1016/S2213-2600(14)70153-5. Epub 2014 Jul 24.

Abstract

Background: Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD.

Methods: This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541.

Findings: Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported.

Interpretation: The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia.

Funding: German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Austria
  • Blood Gas Monitoring, Transcutaneous
  • Female
  • Germany
  • Humans
  • Hypercapnia / blood
  • Hypercapnia / therapy
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Noninvasive Ventilation / methods*
  • Positive-Pressure Respiration / methods*
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT00710541