Clinical trial NCT00668408: LTOT in COPD Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure
Official title: Long-Term Oxygen Therapy (LTOT) in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure (CHF)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Lung Diseases, Obstructive
Chronic Heart Failure
Chronic Hypoxemia
Keywords: OTLT
COPD
CHRONIC HYPOXEMIA
CHF
Lead sponsor: Azienda Ospedaliero-Universitaria Careggi
Sponsor class: OTHER
Collaborators: name: University of Modena and Reggio Emilia
First posted: 2008-04-29
Enrollment: 1000
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The primary outcome of the study is mortality.
timeFrame: 3 years
Secondary outcomes:
measure: 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.
timeFrame: 3 years
Other outcomes:
Locations:
city: Arezzo
country: Italy
facility: Ausl 8 di Arezzo
state: AR
city: Avellino
country: Italy
facility: Azienda Ospedaliera S. G. Moscati
state: AV
city: Bari
country: Italy
facility: A.O. Universitaria Ospedale consorziale policlinico di Bari
state: BA
city: Barletta
country: Italy
facility: Presidio ospedaliero Barletta
state: BA
city: Benevento
country: Italy
facility: Azienda ospedale G. Rummo
state: BN
city: Gussago
country: Italy
facility: Irccs Fondazione Maugeri
state: BS
city: Cagliari
country: Italy
facility: Ospedale Roberto Binaghi
state: CA
city: Iglesias
country: Italy
facility: Presidio Ospedaliero F.lli Crobu Iglesias
state: CI
city: Castrovillari
country: Italy
facility: Asp di Cosenza - Ambito territoriale di Castrovillari (ex asl 2)
state: CS
city: Catanzaro
country: Italy
facility: Asp di Catanzaro - Ambito territoriale di catanzaro (ex asl 7)
state: CZ
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Mater Domini
state: CZ
city: Forlì
country: Italy
facility: Presidio Ospedaliero Morgagni-Pierantoni di Forlì
state: FC
city: Forlì
country: Italy
facility: Presidio Ospedaliero Morgagni-Pierantoni
state: FC
city: Ferrara
country: Italy
facility: A.O. Universitaria Arcispedale S. Anna
state: FE
city: Firenze
country: Italy
facility: A.O. Universitaria Careggi
state: FI
city: Impruneta
country: Italy
facility: Irccs fondazione Don Gnocchi - Centro S. Maria agli ulivi
state: FI
city: Genova
country: Italy
facility: A.O. Universitaria S. Martino
state: GE
city: Grosseto
country: Italy
facility: Ospedale della Misericordia
state: GR
city: Massa Marittima
country: Italy
facility: Ospedale S. Andrea
state: GR
city: Imperia
country: Italy
facility: Stabilimento ospedaliero di Imperia
state: IM
city: Tricase
country: Italy
facility: Ospedale generale prov. card. G. Panico
state: LE
city: Lucca
country: Italy
facility: Ausl 2 di Lucca
state: LU
city: Milano
country: Italy
facility: Ospedale S. Giuseppe f.b.f.
state: MI
city: Vimercate
country: Italy
facility: Ospedale civile di Vimercate
state: MI
city: Mantova
country: Italy
facility: Presidio Ospedaliero C. Poma
state: MN
city: Modena
country: Italy
facility: A.O. Universitaria policlinico di Modena
state: MO
city: Carrara
country: Italy
facility: Ospedale Civile di Carrara
state: MS
city: Palermo
country: Italy
facility: A.O. V. Cervello
state: PA
city: Palermo
country: Italy
facility: Presidio ospedaliero Civico e benfratelli
state: PA
city: Cittadella
country: Italy
facility: Aulss 15 alta padovana
state: PD
city: Padova
country: Italy
facility: Azienda Ospedaliera di padova
state: PD
city: Perugia
country: Italy
facility: A.O. di Perugia - Ospedale S. Maria della Misericordia (ex Silvestrini)
state: PG
city: Perugia
country: Italy
facility: Asl 2 di Perugia
state: PG
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana
state: PI
city: Pordenone
country: Italy
facility: Azienda Ospedaliera S. Maria degli angeli
state: PN
city: Parma
country: Italy
facility: A.O. Universitaria di Parma
state: PR
city: Pistoia
country: Italy
facility: Ausl 3 di Pistoia
state: PT
city: Montescano
country: Italy
facility: Irccs fondazione Maugeri
state: PV
city: Pavia
country: Italy
facility: Irccs Fondazione Maugeri
state: PV
city: Pavia
country: Italy
facility: Irccs policlinico S. Matteo
state: PV
city: Correggio
country: Italy
facility: Ospedale S. Sebastiano
state: RE
city: Reggio nell'Emilia
country: Italy
facility: Ospedale di S. Maria Nuova
state: RE
city: Rieti
country: Italy
facility: Ospedale S. Camillo De Lellis
state: RI
city: Albano Laziale
country: Italy
facility: Ausl rm/h di Albano Laziale
state: RM
city: Roma
country: Italy
facility: A.O. Universitaria Policlinico Tor Vergata
state: RM
city: Roma
country: Italy
facility: Az. Osp. San Camillo-Forlanini
state: RM
city: Roma
country: Italy
facility: Az.osp.san camillo-forlanini -
state: RM
city: Rovigo
country: Italy
facility: Aulss 18 di Rovigo
state: RO
city: Salerno
country: Italy
facility: Asl sa/2 di Salerno
state: SA
city: Siena
country: Italy
facility: A.O. Universitaria senese
state: SI
city: Sarzana
country: Italy
facility: Presidio ospedaliero San Bartolomeo
state: SP
city: Siracusa
country: Italy
facility: Azienda Ospedaliera Umberto I
state: SR
city: Sassari
country: Italy
facility: A.O. Universitaria Policlinico di Sassari
state: SS
city: Pietra Ligure
country: Italy
facility: Az. Osp. Ospedale S. Corona
state: SV
city: Teramo
country: Italy
facility: Ospedale Mazzini
state: TE
city: Trento
country: Italy
facility: Ospedale di Trento - P.O. S.Chiara
state: TN
city: Torino
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette di Torino
state: TO
city: Trieste
country: Italy
facility: A.O. Universitaria ospedali riuniti di Trieste
state: TS
city: Vicenza
country: Italy
facility: Ospedale di
state: VI
city: Bussolengo
country: Italy
facility: Ospedale civile Orlandi Bussolengo
state: VR
city: Firenze
country: Italy
facility: Terapia Intensiva Pneumologica- AOU Careggi
city: Napoli
country: Italy
facility: Azienda ospedaliera "A. Cardarelli"
city: Napoli
country: Italy
facility: Azienda Ospedaliera Antonio Cardarelli di Napoli
city: Napoli
country: Italy
facility: Azienda Ospedaliera Cotugno
city: Novara
country: Italy
facility: A.O. Universitaria Maggiore della Carità
city: Veruno
country: Italy
facility: Irccs Fondazione Maugeri
Study officials:
affiliation: AOU Careggi
name: Antonio Corrado, MD
role: PRINCIPAL_INVESTIGATOR
References: