LTOT in COPD Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Long-Term Oxygen Therapy (LTOT) in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure (CHF)

Conditions
-----------------
Lung Diseases, Obstructive, Chronic Heart Failure, Chronic Hypoxemia

Intervention / Treatment
-----------------
* Other: LTOT (oxygen therapy)
* Other: Pharmacological therapy of COPD and CHF


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: LTOT group<br>Study group: optimal medical therapy plus LTOT = or > 15 hours pro die | Other: LTOT (oxygen therapy)<br>* Patients on LTOT will receive oxygen for at least 15 hours/day from the liquid oxygen systems at a flow rate adjusted to raise resting SaO2 between 93 and 96% and / or PaO2 between 65 and 80 mmHg every day for 3 years.<br>* Other names: LTOT treatment;|
| Other: Non LTOT group<br>control group: optimal medical therapy without LTOT | Other: Pharmacological therapy of COPD and CHF<br>* Optimal pharmacologic treatment will include : Long (LABD, salmeterol, formoterol, tiotropium) - as well as short-acting (SABD, Salbutamol, terbutaline, ipratropium)bronchodilators (beta-2 agonists, anticholinergics) Inhaled steroids (ICS, beclomethasone, fluticasone, budesonide always associated with LABD) Beta-blockers Diuretics Angiotensin-converting enzyme (ACE) inhibitors alone or in associations with diuretics Statins and any other treatment required for associated co-morbidities (eg insulin and/or anti-diabetic drugs, other antihypertensive, etc). The treatment of the deseases will follow the international guidelines.<br>* Other names: Pharmacological treatment;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome of the study is mortality. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoint of the study is to evaluate whether the appropriate medical treatment without LTOT is not inferior to medical treatment with LTOT in terms of quality of life, rate and severity of exacerbation, number of hospital admissions. |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
OTLT, COPD, CHRONIC HYPOXEMIA, CHF