Clinical trial NCT00327873: Palliative Oxygen for the Relief of Breathlessness
Official title: A Multi-center Randomized Double-blind Controlled Trial of Oxygen Versus Medical Air for the Relief of Breathlessness in Patients With Intractable Dyspnea and PaO2>55mmHg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dyspnea
Keywords: breathlessness
shortness of breath
end-of-life care
hospice
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Doris Duke Charitable Foundation
name: Cancer Council Tasmania
name: Duke Institute on Care at the End of Life, USA
name: Flinders Medical Research Institute Small Research Grants Scheme, Australia
First posted: 2006-05-19
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this study is to establish the effectiveness of palliative oxygen in the context within which it is usually provided--relief of the sensation of breathlessness and improvement in quality of life for people with maximally-treated life-limiting illness.

Detailed description: When further medical management will not relieve intractable breathlessness, palliative oxygen is often prescribed regardless of whether the person meets the common oxygen funding criteria of severely low blood oxygen levels. The results of this study will inform best practice in the care of people with advanced life-limiting illness and intractable breathlessness, aid in the development of rational funding guidelines, and answer an international debate on the role of palliative oxygen.

This study is a definitive international multi-center randomized double-blind controlled trial of oxygen versus medical air for the relief of breathlessness in participants with intractable dyspnea and PaO2\>55mmHg (a measure of blood oxygen levels). Specific aims include demonstration of the effectiveness of oxygen versus medical air in relieving breathlessness in the palliative setting (Specific Aim 1) and improving QOL (Specific Aim 2). Additionally, we will seek to establish which patients derive the greatest benefit (Specific Aim 3), the risks of therapy (Specific Aim 4), and the costs of therapy (Specific Aim 5). The primary hypothesis is that oxygen therapy is superior to air in relieving the sensation of breathlessness for patients with intractable dyspnea due to life-limiting illness in the setting of PaO2\>55mmHg.

All participants are enrolled as outpatients. The "eligibility visit" occurs about 5-7 days before starting the study and will include review of the consent form, a short interview, physical exam, and blood tests. The visit can occur in the home or clinic. The blood tests include regular venipuncture and also an arterial blood gas, if these studies have not been done in the preceding month. The "randomization visit" occurs 2 days before the study starts (Day -2) and includes a short interview and quality of life (QOL) questionnaire; this visit is usually done in the home but can also occur in the clinic. The oxygen or air concentrators are delivered to the home on Day 0 by a trained person from the oxygen company. On the same day there is also a brief home visit from the study nurse that includes a short interview and QOL questionnaire. The participant uses the oxygen or medical air gas each of 7 days (Days 0-6) for at least 15 hours each day. While using the oxygen/air the participant fills out a short diary form in the morning and evening, within 30 minutes of waking up or retiring. The diary focuses on the breathlessness, how the participant is feeling, and potential side effects of the gas. The study nurse conducts a "check-in" telephone call on Day 3 to make sure the participant is doing OK. On the last day (Day 6) the nurse visits the home to conduct a brief interview with a short QOL questionnaire. The oxygen company will pick up the concentrator, usually on Day 7.

Eligibility criteria: Inclusion Criteria:

* Adult patients with intractable dyspnea and PaO2\>55mmHg in the setting of terminal illness where the underlying cause has been maximally treated; a medical specialist must document that all identified reversible causes of the dyspnea have been treated; PaO2 measurement must be in the last month
* Dyspnea at rest or with minimal exertion, as measured by a score of ≥ 3 on the Medical Research Council categorical dyspnea exertion scale
* On stable medications over the prior week except routine "as needed" medications.
* Survival of at least 1 month in the opinion of the treating physician

Exclusion Criteria:

* Meets international guidelines for long-term oxygen therapy with PaO2 56-59mmHg, i.e. symptomatic pulmonary hypertension with cor pulmonale
* Hemoglobin\<10.0g/dL as measured within one month of baseline evaluation
* PaCO2 \>50 mm Hg.
* Confusion as measured by Folstein Mini-mental Status Exam \<24/30
* Current oxygen therapy or continuous oxygen therapy in previous week
* Actively smoking
* Active respiratory or cardiac event in the previous 2 weeks, not including upper respiratory tract infections; illness must be resolved for at least 2 weeks prior to baseline evaluation, as judged by a doctor involved in the care of the patient
* Previous respiratory failure induced by oxygen
* Unable to give informed consent or complete diary entries

Primary outcomes:
measure: Changes in relief from the sensation of breathlessness
timeFrame: 7 days
Secondary outcomes:
measure: Changes in quality of life (QOL)
timeFrame: 7 days
measure: Identification of patients who benefit from palliative oxygen
timeFrame: 7 days
measure: Identification of side effects
timeFrame: 7 days
measure: Documentation of costs of palliative oxygen
timeFrame: 7 days
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Department of Medicine, Division of Medical Oncology
state: North Carolina
city: Sydney
country: Australia
facility: Sydney Area Health Service, Sydney Cancer Centre
state: New South Wales
city: Adelaide
country: Australia
facility: Flinders University, Southern Adelaide Palliative Services
state: South Australia
city: Launceston
country: Australia
facility: Statewide Palliative Care Service
state: Tasmania
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Cambridge
country: United Kingdom
facility: St Nicholas Hospice
city: Nottingham
country: United Kingdom
facility: Nottingham University
Study officials:
affiliation: Duke University
name: Amy Abernethy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Flinders University, Australia
name: David Curow, BMed,FRACP,MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abernethy AP, Currow DC, Frith P, Fazekas B. Prescribing palliative oxygen: a clinician survey of expected benefit and patterns of use. Palliat Med. 2005 Mar;19(2):168-70. doi: 10.1177/026921630501900219. No abstract available.
citation: Booth S, Wade R, Johnson M, Kite S, Swannick M, Anderson H; Expert Working Group of the Scientific Committee of the Association of Palliative Medicine. The use of oxygen in the palliation of breathlessness. A report of the expert working group of the Scientific Committee of the Association of Palliative Medicine. Respir Med. 2004 Jan;98(1):66-77. doi: 10.1016/j.rmed.2003.08.008.
citation: Guyatt GH, McKim DA, Austin P, Bryan R, Norgren J, Weaver B, Goldstein RS. Appropriateness of domiciliary oxygen delivery. Chest. 2000 Nov;118(5):1303-8. doi: 10.1378/chest.118.5.1303.
citation: Bruera E, Sweeney C, Willey J, Palmer JL, Strasser F, Morice RC, Pisters K. A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea. Palliat Med. 2003 Dec;17(8):659-63. doi: 10.1191/0269216303pm826oa.
citation: Abernethy AP, McDonald CF, Frith PA, Clark K, Herndon JE 2nd, Marcello J, Young IH, Bull J, Wilcock A, Booth S, Wheeler JL, Tulsky JA, Crockett AJ, Currow DC. Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet. 2010 Sep 4;376(9743):784-93. doi: 10.1016/S0140-6736(10)61115-4.