Emphysema, Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Emphysema, Phosphodiesterase inhibitors, Sildenafil, Exercise testing, Quality of life
Brief summary
The purpose of this study is to determine if sildenafil improves the exercise capacity and lung function of patients with chronic obstructive pulmonary disease.
Detailed description
Patients with chronic obstructive pulmonary disease (COPD) suffer from impaired exercise capacity and quality-of-life, largely related to shortness of breath. Many of the therapies currently available for COPD are aimed at improving these factors. Exercise capacity is limited in part by high blood pressure in the blood vessels in the lungs. Sildenafil, also known as Viagra, is an FDA-approved therapy for male erectile dysfunction. One of its effects is to relax (or open) the lung vessels, thereby lowering the blood pressure in the lungs. We hypothesize that sildenafil will result in an improvement in exercise capacity, quality-of-life, and shortness of breath. Enrolled subjects will receive sildenafil or placebo for 4 weeks followed by exercise tests, breathing tests, and administration of quality-of-life questionnaires. Subjects will then receive placebo or sildenafil (whichever one they did not receive for the first 4 weeks) for another 4 weeks, followed by the same testing.
Interventions
DRUGsildenafil citrate
sildenafil citrate 25 mg by mouth thrice daily (po tid)
DRUGPlacebo
25 mg po tid
Sponsors
Pfizer
Kawut, Steven, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of chronic obstructive pulmonary disease (COPD) or emphysema * FEV1/FVC ratio \< 70% * FEV1 \< 80% * Stable medication regimen
Exclusion criteria
* COPD exacerbation or hospitalization in the past 3 months * Heart disease * Contraindication to sildenafil * Unrelated lung disease * Inability to walk or pedal on a stationary bike * Pregnancy or breast-feeding * Pulmonary hypertension at rest
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minute Walk Distance | Period 1 and Period 3 ( within 8 weeks) | The distance a subject walked within 6 minutes was measured and documented. |
| VO2 Peak (Oxygen Consumption at Peak Exercise) | Period 1 and Period 3 ( within 8 weeks) | Oxygen consumption at peak exercise was measured at scheduled timepoints during treatment periods 1 and 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT) | Period 1 and Period 3 ( within 8 weeks) | Participants were asked to scale the breathlessness felt at the end of 6MWT from 0 to 10, with 0 being the least discomfort and 10 being the most discomfort in breathing. |
| Diffusing Capacity of Carbon Monoxide (DLCO) | Period 1 and Period 3 ( within 8 weeks) | Carbon Monoxide Diffusing Capacity was measured on the same days as the pulmonary function tests. |
| Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG) | Period 1 and Period 3 ( within 8 weeks) | Partial pressure of carbon dioxide in ABG performed breathing room air at rest. |
| Pulmonary Function FVC (Forced Vital Capacity) | Period 1 (4 weeks) | Data to calculate results for FVC was based on Period 1. |
| A-a Gradient (Alveolar-arterial Gradient) | Period 1 and Period 3 ( within 8 weeks) | A-a gradient was measured with ABG breathing room air at rest. |
| Oxygen Pulse | Period 1 and Period 3 ( within 8 weeks) | Oxygen pulse during Cardiopulmonary exercise test at peak exercise. |
| O2 Saturation at Peak Exercise | Period 1 and Period 3 ( within 8 weeks) | O2 Saturation at Peak Exercise measured during the Cardiopulmonary exercise test. |
| Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG) | Period 1 and Period 3 ( within 8 weeks) | Partial Pressure of Oxygen in ABG breathing room air at rest. |
| Forced Expiratory Volume in the First Second (FEV1 ) | Period 1 ( 4 weeks) | The volume of air exhaled in the first second. Data to calculate results for FEV1 was based on Period 1 only. |
Countries
United States
Participant flow
Recruitment details
The recruitment period began in February 2005 and ended by November 2008.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Participants All enrolled and randomized participants who were administered 25 mg Sildenafil and 25mg placebo at 2 different time periods. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: ( TREATMENT: 4 Weeks) | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 1 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
6 Minute Walk Distance
The distance a subject walked within 6 minutes was measured and documented.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | 6 Minute Walk Distance | 458.2 meters |
| Placebo | 6 Minute Walk Distance | 466.1 meters |
Primary
VO2 Peak (Oxygen Consumption at Peak Exercise)
Oxygen consumption at peak exercise was measured at scheduled timepoints during treatment periods 1 and 3.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | VO2 Peak (Oxygen Consumption at Peak Exercise) | 13.7 ml/kg/min |
| Placebo | VO2 Peak (Oxygen Consumption at Peak Exercise) | 13.8 ml/kg/min |
Secondary
A-a Gradient (Alveolar-arterial Gradient)
A-a gradient was measured with ABG breathing room air at rest.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | A-a Gradient (Alveolar-arterial Gradient) | 25 mm Hg |
| Placebo | A-a Gradient (Alveolar-arterial Gradient) | 23 mm Hg |
Secondary
Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT)
Participants were asked to scale the breathlessness felt at the end of 6MWT from 0 to 10, with 0 being the least discomfort and 10 being the most discomfort in breathing.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT) | 3.9 Scores on a scale |
| Placebo | Borg Dyspnea(Scale That Measures Breathlessness) Score at Finish of 6 Minute Walk Test (6MWT) | 3.8 Scores on a scale |
Secondary
Diffusing Capacity of Carbon Monoxide (DLCO)
Carbon Monoxide Diffusing Capacity was measured on the same days as the pulmonary function tests.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Diffusing Capacity of Carbon Monoxide (DLCO) | 11 ml/min/torr |
| Placebo | Diffusing Capacity of Carbon Monoxide (DLCO) | 11 ml/min/torr |
Secondary
Forced Expiratory Volume in the First Second (FEV1 )
The volume of air exhaled in the first second. Data to calculate results for FEV1 was based on Period 1 only.
Time frame: Period 1 ( 4 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Forced Expiratory Volume in the First Second (FEV1 ) | 1.1 liters |
| Placebo | Forced Expiratory Volume in the First Second (FEV1 ) | 1.1 liters |
Secondary
O2 Saturation at Peak Exercise
O2 Saturation at Peak Exercise measured during the Cardiopulmonary exercise test.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | O2 Saturation at Peak Exercise | 95 percentage of oxygen saturation |
| Placebo | O2 Saturation at Peak Exercise | 96 percentage of oxygen saturation |
Secondary
Oxygen Pulse
Oxygen pulse during Cardiopulmonary exercise test at peak exercise.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Oxygen Pulse | 8.7 ml/beat |
| Placebo | Oxygen Pulse | 9.5 ml/beat |
Secondary
Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG)
Partial pressure of carbon dioxide in ABG performed breathing room air at rest.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG) | 42 mm Hg |
| Placebo | Partial Pressure of Carbon Dioxide (PCO2) in Arterial Blood Gas (ABG) | 40 mm Hg |
Secondary
Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG)
Partial Pressure of Oxygen in ABG breathing room air at rest.
Time frame: Period 1 and Period 3 ( within 8 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG) | 73 mm Hg |
| Placebo | Partial Pressure of Oxygen (PO2) in Arterial Blood Gas (ABG) | 77 mm Hg |
Secondary
Pulmonary Function FVC (Forced Vital Capacity)
Data to calculate results for FVC was based on Period 1.
Time frame: Period 1 (4 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sildenafil | Pulmonary Function FVC (Forced Vital Capacity) | 2.8 liters |
| Placebo | Pulmonary Function FVC (Forced Vital Capacity) | 2.8 liters |