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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Diseases, Obstructive; Chronic Heart Failure; Chronic Hypoxemia
• Intervention / Treatment: Other: LTOT (oxygen therapy); Other: Pharmacological therapy of COPD and CHF

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 Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Antonio Corrado, MD; Phone Number: 055 39-055-794-6559; Email: corradoa@aou-careggi.toscana.it
• Study Contact Backup: Name: Teresa Renda, MD, PhD; Phone Number: 39-328-977-9239; Email: rendateresa@hotmail.it

Study Locations

• Italy
  • Firenze, Italy, 50134
    • Recruiting
    • Terapia Intensiva Pneumologica- AOU Careggi
    • Contact: Antonio Corrado, MD; Phone Number: 055 39-055-794-6559; Email: corradoa@aou-careggi.toscana.it
    • Contact: Teresa Renda, MD; Phone Number: 39-328-977-9239; Email: rendateresa@hotmail.it
    • Principal Investigator: Antonio Corrado, MD
  • Napoli, Italy
    • Active, not recruiting
    • Azienda Ospedaliera "A. Cardarelli"
  • Napoli, Italy
    • Active, not recruiting
    • Azienda Ospedaliera Antonio Cardarelli di Napoli
  • Napoli, Italy
    • Active, not recruiting
    • Azienda Ospedaliera Cotugno
  • Novara, Italy
    • Active, not recruiting
    • A.O. Universitaria Maggiore della Carità
  • Veruno, Italy
    • Active, not recruiting
    • IRCCS Fondazione Maugeri
  • AR
    • Arezzo, AR, Italy
      • Active, not recruiting
      • Ausl 8 di Arezzo
  • AV
    • Avellino, AV, Italy
      • Active, not recruiting
      • Azienda Ospedaliera S. G. Moscati
  • BA
    • Bari, BA, Italy
      • Recruiting
      • A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
      • Principal Investigator: Renato De Tullio
    • Barletta, BA, Italy
      • Recruiting
      • Presidio ospedaliero Barletta
      • Principal Investigator: Franco Dadduzio
  • BN
    • Benevento, BN, Italy
      • Active, not recruiting
      • Azienda ospedale G. Rummo
  • BS
    • Gussago, BS, Italy
      • Active, not recruiting
      • IRCCS Fondazione Maugeri
  • CA
    • Cagliari, CA, Italy
      • Active, not recruiting
      • Ospedale Roberto Binaghi
  • CI
    • Iglesias, CI, Italy
      • Active, not recruiting
      • Presidio Ospedaliero F.lli Crobu Iglesias
  • CS
    • Castrovillari, CS, Italy
      • Active, not recruiting
      • Asp di Cosenza - Ambito territoriale di Castrovillari (ex asl 2)
  • CZ
    • Catanzaro, CZ, Italy
      • Active, not recruiting
      • Asp di Catanzaro - Ambito territoriale di catanzaro (ex asl 7)
    • Catanzaro, CZ, Italy
      • Active, not recruiting
      • Azienda Ospedaliera Mater Domini
  • FC
    • Forlì, FC, Italy
      • Active, not recruiting
      • Presidio Ospedaliero Morgagni-Pierantoni di Forlì
    • Forlì, FC, Italy
      • Active, not recruiting
      • Presidio Ospedaliero Morgagni-Pierantoni
  • FE
    • Ferrara, FE, Italy
      • Active, not recruiting
      • A.O. Universitaria Arcispedale S. Anna
  • FI
    • Firenze, FI, Italy
      • Recruiting
      • A.O. Universitaria Careggi
      • Principal Investigator: Sandra Nutini
    • Impruneta, FI, Italy
      • Active, not recruiting
      • Irccs fondazione Don Gnocchi - Centro S. Maria agli ulivi
  • GE
    • Genova, GE, Italy
      • Active, not recruiting
      • A.O. Universitaria S. Martino
  • GR
    • Grosseto, GR, Italy
      • Active, not recruiting
      • Ospedale Della Misericordia
    • Massa Marittima, GR, Italy
      • Active, not recruiting
      • Ospedale S. Andrea
  • IM
    • Imperia, IM, Italy
      • Active, not recruiting
      • Stabilimento ospedaliero di Imperia
  • LE
    • Tricase, LE, Italy
      • Active, not recruiting
      • Ospedale generale prov. card. G. Panico
  • LU
    • Lucca, LU, Italy
      • Active, not recruiting
      • Ausl 2 di Lucca
  • MI
    • Milano, MI, Italy
      • Active, not recruiting
      • Ospedale S. Giuseppe f.b.f.
    • Vimercate, MI, Italy
      • Active, not recruiting
      • Ospedale Civile di Vimercate
  • MN
    • Mantova, MN, Italy
      • Active, not recruiting
      • Presidio Ospedaliero C. Poma
  • MO
    • Modena, MO, Italy
      • Active, not recruiting
      • A.O. Universitaria Policlinico Di Modena
  • MS
    • Carrara, MS, Italy
      • Recruiting
      • Ospedale Civile di Carrara
      • Principal Investigator: Rigoletta Vincenti
  • PA
    • Palermo, PA, Italy
      • Active, not recruiting
      • A.O. V. Cervello
    • Palermo, PA, Italy
      • Active, not recruiting
      • Presidio ospedaliero Civico e benfratelli
  • PD
    • Cittadella, PD, Italy
      • Active, not recruiting
      • Aulss 15 alta padovana
    • Padova, PD, Italy
      • Active, not recruiting
      • Azienda Ospedaliera di Padova
  • PG
    • Perugia, PG, Italy
      • Active, not recruiting
      • A.O. di Perugia - Ospedale S. Maria della Misericordia (ex Silvestrini)
    • Perugia, PG, Italy
      • Active, not recruiting
      • Asl 2 di Perugia
  • PI
    • Pisa, PI, Italy
      • Recruiting
      • A.O. Universitaria Pisana
      • Principal Investigator: Pierluigi Paggiaro
  • PN
    • Pordenone, PN, Italy
      • Active, not recruiting
      • Azienda Ospedaliera S. Maria degli Angeli
  • PR
    • Parma, PR, Italy
      • Active, not recruiting
      • A.O. Universitaria Di Parma
  • PT
    • Pistoia, PT, Italy
      • Active, not recruiting
      • Ausl 3 di Pistoia
  • PV
    • Montescano, PV, Italy
      • Active, not recruiting
      • IRCCS Fondazione Maugeri
    • Pavia, PV, Italy
      • Recruiting
      • IRCCS Fondazione Maugeri
      • Principal Investigator: Stefano Nava
    • Pavia, PV, Italy
      • Recruiting
      • IRCCS Policlinico S. Matteo
      • Principal Investigator: Isa Cerveri
  • RE
    • Correggio, RE, Italy
      • Active, not recruiting
      • Ospedale S. Sebastiano
    • Reggio nell'Emilia, RE, Italy
      • Recruiting
      • Ospedale di S. Maria Nuova
      • Principal Investigator: Luigi Zucchi
  • RI
    • Rieti, RI, Italy
      • Active, not recruiting
      • Ospedale S. Camillo De Lellis
  • RM
    • Albano Laziale, RM, Italy
      • Active, not recruiting
      • Ausl rm/h di Albano Laziale
    • Roma, RM, Italy
      • Active, not recruiting
      • A.O. Universitaria Policlinico Tor Vergata
    • Roma, RM, Italy
      • Active, not recruiting
      • Az. Osp. San Camillo-Forlanini
    • Roma, RM, Italy
      • Active, not recruiting
      • Az.osp.san camillo-forlanini -
  • RO
    • Rovigo, RO, Italy
      • Active, not recruiting
      • AULSS 18 di Rovigo
  • SA
    • Salerno, SA, Italy
      • Recruiting
      • Asl sa/2 di Salerno
      • Principal Investigator: Pasquale Capano
  • SI
    • Siena, SI, Italy
      • Active, not recruiting
      • A.O. Universitaria Senese
  • SP
    • Sarzana, SP, Italy
      • Active, not recruiting
      • Presidio ospedaliero San Bartolomeo
  • SR
    • Siracusa, SR, Italy
      • Active, not recruiting
      • Azienda Ospedaliera Umberto I
  • SS
    • Sassari, SS, Italy
      • Active, not recruiting
      • A.O. Universitaria Policlinico Di Sassari
  • SV
    • Pietra Ligure, SV, Italy
      • Active, not recruiting
      • Az. Osp. Ospedale S. Corona
  • TE
    • Teramo, TE, Italy
      • Active, not recruiting
      • Ospedale Mazzini
  • TN
    • Trento, TN, Italy
      • Active, not recruiting
      • Ospedale di Trento - P.O. S.Chiara
  • TO
    • Torino, TO, Italy
      • Active, not recruiting
      • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
  • TS
    • Trieste, TS, Italy
      • Active, not recruiting
      • A.O. Universitaria ospedali riuniti di Trieste
  • VI
    • Vicenza, VI, Italy
      • Active, not recruiting
      • Ospedale di
  • VR
    • Bussolengo, VR, Italy
      • Active, not recruiting
      • Ospedale civile Orlandi Bussolengo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Collaborators: University of Modena and Reggio Emilia
• Investigators: Principal Investigator: Antonio Corrado, MD, AOU Careggi

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): March 1, 2012
• Study Completion (Anticipated): October 1, 2012

Study Registration Dates

• First Submitted: April 28, 2008
• First Submitted That Met QC Criteria: April 28, 2008
• First Posted (Estimate): April 29, 2008

Study Record Updates

• Last Update Posted (Estimate): August 28, 2009
• Last Update Submitted That Met QC Criteria: August 27, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: COPD; CHF; OTLT; CHRONIC HYPOXEMIA
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Heart Failure; Lung Diseases; Lung Diseases, Obstructive; Hypoxia
• Other Study ID Numbers: FARM6YHYW4