Dyspnea, Malignant Neoplasm
Conditions
Brief summary
This randomized phase II trial studies how well high-flow oxygen works in reducing difficulty breathing during exercise (exertional dyspnea) in patients with cancer. Dyspnea is linked to decreased lung function, quality of life, and survival. High-flow oxygen is a device that delivers heated and humidified oxygen through the nose. This may be effective in reducing dyspnea, and may help patients' lungs function better and improve their quality of life.
Detailed description
PRIMARY OBJECTIVES: I. Obtain preliminary estimates of the effect size of oxygen and high flow rate on exertional dyspnea (modified Borg Scale adjusted for work rate and baseline dyspnea). SECONDARY OBJECTIVES: I. Determine the completion rate of a randomized controlled trial of exertional dyspnea in cancer patients. II. Obtain preliminary estimates of the effects of oxygen and flow rate on physiologic function (respiratory rate and oxygen saturation) and exercise capacity (work rate and exercise duration). OUTLINE: All patients undergo a baseline structured exercise session with air. Patients are then randomized to 1 of 4 treatments for a second session approximately 3 days later. ARM I: Patients receive high-flow oxygen via nasal prongs during a structured stationary bicycle exercise session. ARM II: Patients receive high-flow air via nasal prongs during a structured stationary bicycle exercise session. ARM III: Patients receive low-flow oxygen via a nasal cannula during a structured stationary bicycle exercise session. ARM IV: Patients receive low-flow air via a nasal cannula during structured stationary bicycle exercise session.
Interventions
PROCEDUREOxygen Therapy
Receive high-flow oxygen
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURERespiratory Therapy
Receive low-flow oxygen
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of cancer, with evidence of primary or secondary lung involvement * Average dyspnea Borg Scale \>= 4 of 10 with severe exertion over the past week * Oxygen saturation \> 90% on ambient air at time of assessment * Able to communicate in English or Spanish * Karnofsky performance status \>= 50% * Seen at Supportive Care, cardiopulmonary center, thoracic radiation oncology or thoracic medical oncology
Exclusion criteria
* Resting dyspnea modified Borg Scale \> 7 of 10 at enrollment * Severe obstructive lung disease (forced expiratory volume in 1 second \[FEV1\]/forced vital capacity \[FVC\] \< 70% post bronchodilator and forced expiratory volume in 1 second \< 30% predicted) * Delirium (i.e., Memorial Delirium Rating Scale \> 13) * History of unstable angina or myocardial infarction in the last week * Acute pulmonary embolus or pulmonary infarction in the last week * Thrombosis of lower extremities in the last week * Acute myocarditis, pericarditis, or endocarditis in the last week * Symptomatic aortic stenosis or syncope in the last week * Suspected dissecting aneurysm * Severe untreated resting arterial hypertension (\> 200 mmHg systolic, \> 120 mmHg diastolic) at the time of enrollment * Uncontrolled arrhythmias causing symptoms or hemodynamic compromise in the last week * Uncontrolled heart failure in the last week * Pleural effusion requiring thoracentesis within 1 week of study enrollment or scheduled during the study period * Airway obstruction requiring stenting within 1 week of study enrollment or scheduled during the study period * Pneumonia requiring antibiotics at the time of study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Borg Scale Dyspnea Intensity at Isotime | End of second exercise test and end of third exercise test, approximately up to 12 minutes | Assessed Dyspnea using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath) at Isotime. Measured the mean difference of Modified Borg Scale Dyspnea Intensity at isotime between the second exercise test (in which all patients received Low Flow Oxygen) and the third exercise tests (in which all patients received the assigned intervention). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | Third exercise test, approximately up to 12 minutes | Dyspnea unpleasantness was measured using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Dyspnea intensity was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Dyspnea Unpleasantness at third test = Minutes + Study Arm + Study Arm\*Minutes + Total work rate + Slope of Dyspnea Unpleasantness and Minutes at Second test + Minutes at second test. |
| Modified Borg Scale Leg Discomfort | Third exercise test, approximately up to 12 minutes | Leg discomfort was measured using the Modified Borg Scale Leg discomfort that ranges from 0 (no discomfort) to 10 (worst possible discomfort) during the constant work exercise of third test. Leg discomfort was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Leg Discomfort at third test = Minutes + Study Arm + Study Arm\*Minutes + Total work rate + Slope of Leg Discomfort and Minutes at Second test + Minutes at Second test. |
| Exercise Endurance | End of third exercise test, approximately up to 12 minutes | The Exercise endurance was measured as a mean duration of constant work in minutes during third test. It was measured as pairwise comparison of mean difference of exercise duration (taking 'low flow air' as a reference). This linear mixed model was constructed based on the following: Time at third test = Study Arm + Minutes at Second test. Detail output from the mixed models |
| Adverse Events | Before and after 3rd test during intervention phase, approximately up to 12 minutes | Adverse effects related to supplemental oxygen use were assessed using a numeric rating scale from 0 (not at all) to 10 (worst possible) before and after the study intervention. The mean change was measured before and after the 3rd test ranging between -10 (improvement) and +10 (deterioration). |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the Supportive Care, Thoracic Radiation Oncology and Thoracic Medical Oncology clinics at MD Anderson Cancer Center, Houston, USA between 3/2015 and 4/2018 .
Pre-assignment details
A total of 74 participants were enrolled but 45 patients were randomized for this study. 29 patients were not randomized for various reasons (became ineligible or too symptomatic to participate while waiting=14, scheduling conflict=9, exertional dyspnea too low=4, could not complete baseline test due to desaturation=1, hypertension during exercise=1)
Participants by arm
| Arm | Count |
|---|---|
| High Flow Oxygen High Flow Oxygen were delivered between 20 and 70 L/min | 10 |
| High Flow Air High Flow Air were delivered between 20 and 70 L/min | 11 |
| Low Flow Oxygen Low Flow Oxygen were delivered at 2 L/min | 12 |
| Low Flow Air Low Flow Air were delivered at 2 L/min | 11 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | High Flow Air | High Flow Oxygen | Total | Low Flow Air | Low Flow Oxygen |
|---|---|---|---|---|---|
| Age, Continuous | 67 years | 59 years | 63 years | 62 years | 63 years |
| Cancer Stage Localized | 3 Participants | 1 Participants | 7 Participants | 0 Participants | 3 Participants |
| Cancer Stage Locally advanced | 4 Participants | 3 Participants | 17 Participants | 6 Participants | 4 Participants |
| Cancer Stage Metastatic | 4 Participants | 6 Participants | 20 Participants | 5 Participants | 5 Participants |
| Cancer Type Mesothelioma | 0 Participants | 0 Participants | 5 Participants | 3 Participants | 2 Participants |
| Cancer Type Non Small Cell Lung Cancer | 9 Participants | 7 Participants | 28 Participants | 5 Participants | 7 Participants |
| Cancer Type Other | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 1 Participants |
| Cancer Type Small Cell Lung Cancer | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 2 Participants |
| Comorbidities Asthma | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Comorbidities COPD | 3 Participants | 5 Participants | 11 Participants | 1 Participants | 2 Participants |
| Comorbidities Heart Failure | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 4 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 40 Participants | 9 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 7 Participants | 38 Participants | 10 Participants | 11 Participants |
| Region of Enrollment United States | 11 participants | 10 participants | 44 participants | 11 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 18 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 26 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Modified Borg Scale Dyspnea Intensity at Isotime
Assessed Dyspnea using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath) at Isotime. Measured the mean difference of Modified Borg Scale Dyspnea Intensity at isotime between the second exercise test (in which all patients received Low Flow Oxygen) and the third exercise tests (in which all patients received the assigned intervention).
Time frame: End of second exercise test and end of third exercise test, approximately up to 12 minutes
Population: The data is provided for 44 participants who completed the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Flow Oxygen | Modified Borg Scale Dyspnea Intensity at Isotime | -1.1 score on a scale |
| High Flow Air | Modified Borg Scale Dyspnea Intensity at Isotime | -0.2 score on a scale |
| Low Flow Oxygen | Modified Borg Scale Dyspnea Intensity at Isotime | -1.8 score on a scale |
| Low Flow Air | Modified Borg Scale Dyspnea Intensity at Isotime | -0.5 score on a scale |
Secondary
Adverse Events
Adverse effects related to supplemental oxygen use were assessed using a numeric rating scale from 0 (not at all) to 10 (worst possible) before and after the study intervention. The mean change was measured before and after the 3rd test ranging between -10 (improvement) and +10 (deterioration).
Time frame: Before and after 3rd test during intervention phase, approximately up to 12 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Flow Oxygen | Adverse Events | Dry eyes | 0 units on a scale | Standard Deviation 0 |
| High Flow Oxygen | Adverse Events | Dry Nose | 0 units on a scale | Standard Deviation 0 |
| High Flow Oxygen | Adverse Events | Eye Irritation | -0.1 units on a scale | Standard Deviation 0.32 |
| High Flow Oxygen | Adverse Events | Moisture in nose | 1 units on a scale | Standard Deviation 3.8 |
| High Flow Oxygen | Adverse Events | Nasal Prongs Uncomfortable | -0.3 units on a scale | Standard Deviation 0.67 |
| High Flow Oxygen | Adverse Events | Suffocating | 0.1 units on a scale | Standard Deviation 1.2 |
| High Flow Oxygen | Adverse Events | Anxious | 0.4 units on a scale | Standard Deviation 1.78 |
| High Flow Oxygen | Adverse Events | Difficulty talking | -0.1 units on a scale | Standard Deviation 0.57 |
| High Flow Air | Adverse Events | Suffocating | -0.09 units on a scale | Standard Deviation 0.54 |
| High Flow Air | Adverse Events | Nasal Prongs Uncomfortable | 0.18 units on a scale | Standard Deviation 0.87 |
| High Flow Air | Adverse Events | Dry Nose | -0.45 units on a scale | Standard Deviation 1.21 |
| High Flow Air | Adverse Events | Difficulty talking | 0.09 units on a scale | Standard Deviation 0.3 |
| High Flow Air | Adverse Events | Anxious | -0.55 units on a scale | Standard Deviation 1.29 |
| High Flow Air | Adverse Events | Moisture in nose | 0.73 units on a scale | Standard Deviation 1.56 |
| High Flow Air | Adverse Events | Eye Irritation | 0 units on a scale | Standard Deviation 0 |
| High Flow Air | Adverse Events | Dry eyes | 0 units on a scale | Standard Deviation 0 |
| Low Flow Oxygen | Adverse Events | Anxious | 0.17 units on a scale | Standard Deviation 0.72 |
| Low Flow Oxygen | Adverse Events | Eye Irritation | 0.33 units on a scale | Standard Deviation 1.15 |
| Low Flow Oxygen | Adverse Events | Moisture in nose | 0 units on a scale | Standard Deviation 1.13 |
| Low Flow Oxygen | Adverse Events | Nasal Prongs Uncomfortable | -0.17 units on a scale | Standard Deviation 0.94 |
| Low Flow Oxygen | Adverse Events | Suffocating | 0.08 units on a scale | Standard Deviation 0.29 |
| Low Flow Oxygen | Adverse Events | Difficulty talking | 0 units on a scale | Standard Deviation 0 |
| Low Flow Oxygen | Adverse Events | Dry eyes | 0.17 units on a scale | Standard Deviation 0.94 |
| Low Flow Oxygen | Adverse Events | Dry Nose | -.033 units on a scale | Standard Deviation 0.89 |
| Low Flow Air | Adverse Events | Eye Irritation | 0 units on a scale | Standard Deviation 0 |
| Low Flow Air | Adverse Events | Moisture in nose | 1.5 units on a scale | Standard Deviation 2.8 |
| Low Flow Air | Adverse Events | Dry Nose | 0.3 units on a scale | Standard Deviation 0.67 |
| Low Flow Air | Adverse Events | Dry eyes | 0 units on a scale | Standard Deviation 0 |
| Low Flow Air | Adverse Events | Nasal Prongs Uncomfortable | 0.3 units on a scale | Standard Deviation 0.67 |
| Low Flow Air | Adverse Events | Difficulty talking | 0 units on a scale | Standard Deviation 0 |
| Low Flow Air | Adverse Events | Anxious | 0.5 units on a scale | Standard Deviation 1.58 |
| Low Flow Air | Adverse Events | Suffocating | 0.4 units on a scale | Standard Deviation 0.7 |
Secondary
Exercise Endurance
The Exercise endurance was measured as a mean duration of constant work in minutes during third test. It was measured as pairwise comparison of mean difference of exercise duration (taking 'low flow air' as a reference). This linear mixed model was constructed based on the following: Time at third test = Study Arm + Minutes at Second test. Detail output from the mixed models
Time frame: End of third exercise test, approximately up to 12 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Flow Oxygen | Exercise Endurance | 10.50 minutes |
| High Flow Air | Exercise Endurance | 8.18 minutes |
| Low Flow Oxygen | Exercise Endurance | 7.58 minutes |
| Low Flow Air | Exercise Endurance | 7.36 minutes |
Secondary
Modified Borg Scale Leg Discomfort
Leg discomfort was measured using the Modified Borg Scale Leg discomfort that ranges from 0 (no discomfort) to 10 (worst possible discomfort) during the constant work exercise of third test. Leg discomfort was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Leg Discomfort at third test = Minutes + Study Arm + Study Arm\*Minutes + Total work rate + Slope of Leg Discomfort and Minutes at Second test + Minutes at Second test.
Time frame: Third exercise test, approximately up to 12 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Flow Oxygen | Modified Borg Scale Leg Discomfort | 0.59 Units on a scale per minute |
| High Flow Air | Modified Borg Scale Leg Discomfort | 0.91 Units on a scale per minute |
| Low Flow Oxygen | Modified Borg Scale Leg Discomfort | 0.65 Units on a scale per minute |
| Low Flow Air | Modified Borg Scale Leg Discomfort | 0.81 Units on a scale per minute |
Secondary
Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test)
Dyspnea unpleasantness was measured using the Modified Borg Scale Dyspnea Intensity that ranges from 0 (no shortness of breath) to 10 (worst possible shortness of breath). Dyspnea intensity was measured every minute. The number of minutes varied by patient, per test. It was measured as pairwise difference of slope (taking 'low flow air' arm as a reference). This linear mixed model was constructed based on the following: Dyspnea Unpleasantness at third test = Minutes + Study Arm + Study Arm\*Minutes + Total work rate + Slope of Dyspnea Unpleasantness and Minutes at Second test + Minutes at second test.
Time frame: Third exercise test, approximately up to 12 minutes
Population: The data is provided for 44 participants who completed the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Flow Oxygen | Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | 0.55 Units on a scale per minute |
| High Flow Air | Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | 0.78 Units on a scale per minute |
| Low Flow Oxygen | Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | 0.59 Units on a scale per minute |
| Low Flow Air | Slope of Modified Borg Scale Dyspnea Unpleasantness Over Time During Constant Work Exercise Per Minute (Third Test) | 0.69 Units on a scale per minute |