LTOT in COPD Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure
LTOT in COPD Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure
In patients with both COPD and CHF, moderate chronic hypoxemia is caused by a combination of
 intrapulmonary and extrapulmonary factors. The hypothesis of this study is that adequate
 medical therapy for both conditions can correct the moderate hypoxemia by improving the
 underlying mechanisms without the need of LTOT. If this hypothesis is correct, the study will
 provide a valuable information to the Italian Agency of drugs (Agenzia Italiana del Farmaco,
 AIFA) to reduce the inappropriate use of LTOT for COPD patients with moderate hypoxemia and
 CHF, and will help the Italian National Health Service to reduce both the direct and indirect
 costs of unnecessary LTOT.
Long-term oxygen treatment (LTOT) improves survival of COPD patients with severe hypoxemia .
 The improved survival was proven in COPD patients with severe chronic hypoxemia (PaO2< or =
 55 mmHg), providing oxygen was delivered for = or >15 hours/day. Since then, > 15 hours/day
 LTOT has become the standard treatment for COPD patients with severe hypoxemia. LTOT has been
 extended without evidence to COPD patients with moderate hypoxemia (55< PaO2 <60mmHg), when
 associated with some clinical and laboratory signs of cardiac diseases and to patients with
 decreased oxygen saturation (SO2 < 90%) during exercise or sleep. Chronic heart failure (CHF)
 is a common co-morbidity of COPD (>30% ) particularly in the elderly. Whether LTOT improves
 survival in patients with moderate chronic hypoxemia and CHF is unknown. This is an issue of
 concern because of the potential importance of LTOT in severe COPD, and of the cost of LTOT
 (about Euro 250 millions/year in Italy). The aim of this 3 year randomized clinical trial is
 to investigate whether, in COPD patients with moderate hypoxemia associated with CHF
 treatment including LTOT is no different from treatment without LTOT in term of survival and
 of exacerbations, hospitalizations, and quality of life. The study will be conducted in 76
 Italian hospital pulmonary units, and will start on May 15th 2008 and end on October 31st
 2012. One thousand stable COPD patients treated according to COPD and CHF international
 guidelines will be randomized to treatment including LTOT (Study Group) or treatment without
 LTOT (Control Group). All patients will regularly undergo clinical assessment, arterial blood
 gases (3 monthly), and Saint George's Respiratory Questionnaire (SGRQ, 6 monthly),and will be
 contacted with monthly telephone calls.

 Considering 1) the lack of evidence supporting LTOT in COPD patients with moderate hypoxemia
 and CHF, 2) the pathophysiology of CHF , and 3) the improvement of pharmacological treatment
 of both COPD and CHF, we expect that, after optimization of medical therapy, LTOT will not
 improve survival or frequency and severity of exacerbations and/or hospitalization, and not
 even quality of life due to the balance of small clinical benefits (improved exercise
 tolerance, better sleep) with the inconveniences associated with LTOT. This non-inferiority
 study is powered on survival, which is the primary outcome of the study.
Inclusion Criteria:

 -  Age 40 > 80 years

 -  Confirmed COPD (GOLD criteria)

 -  Moderate and stable hypoxemia (55< PaO2 <65 mmHg)

 -  Clinical signs of CHF (ESC criteria)

 -  Ex-smokers (> 20 pack/years) since at least 3 months

 Exclusion Criteria:

 -  Clinical instability and/or exacerbation

 -  Congenital heart diseases

 -  Lung cancer

 -  Thoracic restrictive disorders

 -  Other coexisting diseases influencing 3-yr survival