Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic obstructive pulmonary disease, sleeping oxygen saturation, sleep quality
Brief summary
The aim of this study was to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD.
Detailed description
Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD. In a randomized, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension \>60 mmHg while awake), we compared the effects of 6 months' treatment with the two devices on sleeping SaO2 and sleep quality.
Interventions
DRUGtiotropium
Comparison of the effect of tiotropium delivered by the Respimat Soft Mist Inhaler versus the HandiHaler on sleeping oxygen saturation and sleep quality in patients with COPD.
DEVICEHandihaler
Inhalation via the HandiHaler once daily
DEVICERespimat
Inhalation via the Respimat once daily
Sponsors
University of Crete
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients aged \>=40 years old * current or ex-smokers with a smoking history of at least 10 pack-years * mild to moderate stable COPD (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Stage I and II according to the 2010 GOLD guidelines (a post-bronchodilator forced expiratory volume in the first second (FEV1) ≥80% of predicted for stage I and 50% ≤ FEV1 \< 80% of predicted for stage II, with a post-bronchodilator FEV1/forced vital capacity (FVC) ratio \<0.70 at screening) * waking arterial oxygen tension (PaO2) ≥60 mmHg
Exclusion criteria
* refusal to participate * respiratory tract infection within 4 weeks prior to screening * COPD exacerbations requiring treatment with antibiotics and/or oral corticosteroids and/or hospitalization within 6 weeks prior to screening * concomitant pulmonary diseases other than COPD * asthma * evidence of sleep apnea on baseline sleep studies * obesity hypoventilation syndrome * respiratory failure * congestive heart failure * a history of life-threatening arrhythmias * cardiomyopathy * long-QT syndrome or QTc \>450 ms at screening * diabetes * long-term oxygen therapy * symptomatic prostatic hyperplasia * bladder-neck obstruction * moderate/severe renal impairment * urinary retention * narrow-angle glaucoma * family or personal history of mental illness * drug or alcohol abuse * severe cognitive impairment * concurrent oncological diseases * history of narcolepsy or restless legs syndrome * known history of alpha-1 antitrypsin deficiency * participation in the active phase of a supervised pulmonary rehabilitation program * hypersensitivity to any of the test ingredients * history of adverse reactions to inhaled anticholinergics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleeping Oxygen Saturation | 6 months after treatment initiation | Mean sleeping oxygen saturation (%) |
| Sleep Quality | 6 months after treatment initiation | Sleep quality, meaning the architecture of sleep (amount of the different sleep stages across the sleep episode),consists of sleep efficiency (%) (total sleep time - TST divided by the total time in bed and multiplied by 100), REM (%TST) (rapid eye movement sleep divided by TST and multiplied by 100) and NREM (%TST) (non-rapid eye movement sleep divided by TST and multiplied by 100). NORMAL RANGES Sleep efficiency: Normal is approximately 85 to 90% or higher. NREM (%TST): 75-80% REM (%TST) normally occupies about 20-25% of sleep time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleepiness | 6 months after treatment initiation | Sleepiness - Epworth Sleepiness Scale (ESS) score (range 0-24, higher values indicate worse outcome, \>10 indicates sleepiness, \>16 excessive sleepiness) |
| Hospitalization Rate | 6 months after treatment initiation | Number of patients needed hospitalization |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Handihaler Tiotropium was delivered by the HandiHaler® device, a single-dose dry powder inhaler
tiotropium: Comparison of the effect of tiotropium delivered by the Respimat Soft Mist Inhaler versus the HandiHaler on sleeping oxygen saturation and sleep quality in patients with COPD.
Handihaler: Inhalation via the HandiHaler once daily | 93 |
| Respimat Tiotropium was delivered via the Respimat® Soft Mist Inhaler,
tiotropium: Comparison of the effect of tiotropium delivered by the Respimat Soft Mist Inhaler versus the HandiHaler on sleeping oxygen saturation and sleep quality in patients with COPD.
Respimat: Inhalation via the Respimat once daily | 95 |
| Total | 188 |
Baseline characteristics
| Characteristic | Handihaler | Respimat | Total |
|---|---|---|---|
| Age, Continuous | 53.7 Years STANDARD_DEVIATION 11.3 | 54.9 Years STANDARD_DEVIATION 11.8 | 54.3 Years STANDARD_DEVIATION 11.5 |
| Region of Enrollment Greece | 93 participants | 95 participants | 188 participants |
| Sex: Female, Male Female | 30 Participants | 25 Participants | 55 Participants |
| Sex: Female, Male Male | 63 Participants | 70 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 93 | 0 / 95 |
| serious Total, serious adverse events | 0 / 93 | 0 / 95 |
Outcome results
Primary
Sleeping Oxygen Saturation
Mean sleeping oxygen saturation (%)
Time frame: 6 months after treatment initiation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Handihaler | Sleeping Oxygen Saturation | 94.4 percentage of Oxygen Saturation | Standard Deviation 2.4 |
| Respimat | Sleeping Oxygen Saturation | 94.4 percentage of Oxygen Saturation | Standard Deviation 2.2 |
p-value: 0.88t-test, 1 sided
Primary
Sleep Quality
Sleep quality, meaning the architecture of sleep (amount of the different sleep stages across the sleep episode),consists of sleep efficiency (%) (total sleep time - TST divided by the total time in bed and multiplied by 100), REM (%TST) (rapid eye movement sleep divided by TST and multiplied by 100) and NREM (%TST) (non-rapid eye movement sleep divided by TST and multiplied by 100). NORMAL RANGES Sleep efficiency: Normal is approximately 85 to 90% or higher. NREM (%TST): 75-80% REM (%TST) normally occupies about 20-25% of sleep time.
Time frame: 6 months after treatment initiation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Handihaler | Sleep Quality | sleep efficiency (%) | 73.2 percentage of time | Standard Deviation 11.8 |
| Handihaler | Sleep Quality | NREM (%TST) | 87.3 percentage of time | Standard Deviation 4.9 |
| Handihaler | Sleep Quality | REM (%TST) | 12.7 percentage of time | Standard Deviation 4.9 |
| Respimat | Sleep Quality | REM (%TST) | 14.7 percentage of time | Standard Deviation 5.2 |
| Respimat | Sleep Quality | sleep efficiency (%) | 79.1 percentage of time | Standard Deviation 13.4 |
| Respimat | Sleep Quality | NREM (%TST) | 85.3 percentage of time | Standard Deviation 5.2 |
Secondary
Hospitalization Rate
Number of patients needed hospitalization
Time frame: 6 months after treatment initiation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Handihaler | Hospitalization Rate | 0 participants |
| Respimat | Hospitalization Rate | 0 participants |
Secondary
Sleepiness
Sleepiness - Epworth Sleepiness Scale (ESS) score (range 0-24, higher values indicate worse outcome, \>10 indicates sleepiness, \>16 excessive sleepiness)
Time frame: 6 months after treatment initiation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Handihaler | Sleepiness | 6.5 units on a scale | Standard Deviation 5.9 |
| Respimat | Sleepiness | 6.1 units on a scale | Standard Deviation 5.8 |