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

Chronic Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00668408
• Other study ID #: FARM6YHYW4
• Status: Recruiting
• Phase: Phase 4
• First received: April 28, 2008
• Last updated: August 27, 2009
• Start date: May 2008
• Est. completion date: October 2012

Study information

• Verified date: August 2009
• Source: Azienda Ospedaliero-Universitaria Careggi
• Contact: Antonio Corrado, MD
• Phone: 39-055-794-6559
• Email: corradoa[@]aou-careggi.toscana.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: October 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Chronic Hypoxemia
• Heart Failure
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Careggi	University of Modena and Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome of the study is mortality.		3 years	No
Secondary	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	No