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

Sponsor

Azienda Ospedaliero-Universitaria Careggi (Other)

Overall Status

Unknown status

CT.gov ID

NCT00668408

Collaborator

University of Modena and Reggio Emilia (Other)

1,000

Enrollment

Locations

Arms

Duration (Months)

15.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Diseases, Obstructive Chronic Heart Failure Chronic Hypoxemia	Other: LTOT (oxygen therapy) Other: Pharmacological therapy of COPD and CHF	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2008

Anticipated Primary Completion Date :

Mar 1, 2012

Anticipated Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: LTOT group Study group: optimal medical therapy plus LTOT = or > 15 hours pro die	Other: LTOT (oxygen therapy) 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. Other Names: LTOT treatment
Other: Non LTOT group control group: optimal medical therapy without LTOT	Other: Pharmacological therapy of COPD and CHF 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. Other Names: Pharmacological treatment

Arm

Intervention/Treatment

Other: LTOT group

Study group: optimal medical therapy plus LTOT = or > 15 hours pro die

Other: LTOT (oxygen therapy)

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.

Other Names:

LTOT treatment

Other: Non LTOT group

control group: optimal medical therapy without LTOT

Other: Pharmacological therapy of COPD and CHF

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.

Other Names:

Pharmacological treatment

Outcome Measures

Primary Outcome Measures

The primary outcome of the study is mortality. [3 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ausl 8 di Arezzo	Arezzo	AR	Italy
2	Azienda Ospedaliera S. G. Moscati	Avellino	AV	Italy
3	A.O. Universitaria Ospedale consorziale policlinico di Bari	Bari	BA	Italy
4	Presidio ospedaliero Barletta	Barletta	BA	Italy
5	Azienda ospedale G. Rummo	Benevento	BN	Italy
6	Irccs Fondazione Maugeri	Gussago	BS	Italy
7	Ospedale Roberto Binaghi	Cagliari	CA	Italy
8	Presidio Ospedaliero F.lli Crobu Iglesias	Iglesias	CI	Italy
9	Asp di Cosenza - Ambito territoriale di Castrovillari (ex asl 2)	Castrovillari	CS	Italy
10	Asp di Catanzaro - Ambito territoriale di catanzaro (ex asl 7)	Catanzaro	CZ	Italy
11	Azienda Ospedaliera Mater Domini	Catanzaro	CZ	Italy
12	Presidio Ospedaliero Morgagni-Pierantoni di Forlì	Forlì	FC	Italy
13	Presidio Ospedaliero Morgagni-Pierantoni	Forlì	FC	Italy
14	A.O. Universitaria Arcispedale S. Anna	Ferrara	FE	Italy
15	A.O. Universitaria Careggi	Firenze	FI	Italy
16	Irccs fondazione Don Gnocchi - Centro S. Maria agli ulivi	Impruneta	FI	Italy
17	A.O. Universitaria S. Martino	Genova	GE	Italy
18	Ospedale della Misericordia	Grosseto	GR	Italy
19	Ospedale S. Andrea	Massa Marittima	GR	Italy
20	Stabilimento ospedaliero di Imperia	Imperia	IM	Italy
21	Ospedale generale prov. card. G. Panico	Tricase	LE	Italy
22	Ausl 2 di Lucca	Lucca	LU	Italy
23	Ospedale S. Giuseppe f.b.f.	Milano	MI	Italy
24	Ospedale civile di Vimercate	Vimercate	MI	Italy
25	Presidio Ospedaliero C. Poma	Mantova	MN	Italy
26	A.O. Universitaria policlinico di Modena	Modena	MO	Italy
27	Ospedale Civile di Carrara	Carrara	MS	Italy
28	A.O. V. Cervello	Palermo	PA	Italy
29	Presidio ospedaliero Civico e benfratelli	Palermo	PA	Italy
30	Aulss 15 alta padovana	Cittadella	PD	Italy
31	Azienda Ospedaliera di padova	Padova	PD	Italy
32	A.O. di Perugia - Ospedale S. Maria della Misericordia (ex Silvestrini)	Perugia	PG	Italy
33	Asl 2 di Perugia	Perugia	PG	Italy
34	A.O. Universitaria Pisana	Pisa	PI	Italy
35	Azienda Ospedaliera S. Maria degli angeli	Pordenone	PN	Italy
36	A.O. Universitaria di Parma	Parma	PR	Italy
37	Ausl 3 di Pistoia	Pistoia	PT	Italy
38	Irccs fondazione Maugeri	Montescano	PV	Italy
39	Irccs Fondazione Maugeri	Pavia	PV	Italy
40	Irccs policlinico S. Matteo	Pavia	PV	Italy
41	Ospedale S. Sebastiano	Correggio	RE	Italy
42	Ospedale di S. Maria Nuova	Reggio nell'Emilia	RE	Italy
43	Ospedale S. Camillo De Lellis	Rieti	RI	Italy
44	Ausl rm/h di Albano Laziale	Albano Laziale	RM	Italy
45	A.O. Universitaria Policlinico Tor Vergata	Roma	RM	Italy
46	Az. Osp. San Camillo-Forlanini	Roma	RM	Italy
47	Az.osp.san camillo-forlanini -	Roma	RM	Italy
48	Aulss 18 di Rovigo	Rovigo	RO	Italy
49	Asl sa/2 di Salerno	Salerno	SA	Italy
50	A.O. Universitaria senese	Siena	SI	Italy
51	Presidio ospedaliero San Bartolomeo	Sarzana	SP	Italy
52	Azienda Ospedaliera Umberto I	Siracusa	SR	Italy
53	A.O. Universitaria Policlinico di Sassari	Sassari	SS	Italy
54	Az. Osp. Ospedale S. Corona	Pietra Ligure	SV	Italy
55	Ospedale Mazzini	Teramo	TE	Italy
56	Ospedale di Trento - P.O. S.Chiara	Trento	TN	Italy
57	A.O. Universitaria S. Giovanni Battista-Molinette di Torino	Torino	TO	Italy
58	A.O. Universitaria ospedali riuniti di Trieste	Trieste	TS	Italy
59	Ospedale di	Vicenza	VI	Italy
60	Ospedale civile Orlandi Bussolengo	Bussolengo	VR	Italy
61	Terapia Intensiva Pneumologica- AOU Careggi	Firenze		Italy	50134
62	Azienda ospedaliera "A. Cardarelli"	Napoli		Italy
63	Azienda Ospedaliera Antonio Cardarelli di Napoli	Napoli		Italy
64	Azienda Ospedaliera Cotugno	Napoli		Italy
65	A.O. Universitaria Maggiore della Carità	Novara		Italy
66	Irccs Fondazione Maugeri	Veruno		Italy