COPD, COPD Exacerbation, COPD Exacerbation Acute, Pollution Related Respiratory Disorder, Pollution; Exposure
Conditions
Keywords
Biomass Associated COPD, Low-dose Theophylline
Brief summary
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, and over 90% of COPD-related deaths occurring in low- and middle-income countries (LMICs). Household air pollution (HAP) - from burning solid fuels such as wood, dung, agricultural crop waste, and coal for energy - is the primary risk factor for COPD in these settings. Biomass-related COPD has a distinct histopathology, phenotype and inflammatory profile when compared to tobacco mediated COPD. Despite the high global burden of biomass-related disease, little is known about the effectiveness of pharmacotherapies for biomass-related COPD; to date, no clinical trials have focused specifically on treatment of biomass-related COPD. This study proposes to assess the health impact of biomass-related COPD and test the effectiveness of low dose theophylline compared to standard therapy among adults with biomass-related COPD in Uganda with the aim to assess whether low-dose theophylline improves respiratory symptoms, decreases the inflammatory profile of serum biomarkers and whether administration attenuates the effect of HAP on lung function. The study additionally aims to assess whether low-dose theophylline is a cost-effective intervention based on the incremental cost-effectiveness ratio and a range of willingness to pay thresholds.
Interventions
DRUGTheophylline ER
200 mg extended release (ER) low-dose theophylline taken orally daily
DRUGPlacebo oral tablet
Manufactured methylcellulose placebo tablet taken orally daily
OTHERStandard of Care Treatment
Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 40 years 2. Full-time resident of study area 3. Post-bronchodilator FEV1/FVC \< the lower limit of normal of the Global Lung Initiative Mixed Ethnic reference population 4. Grade B-D COPD 5. Daily biomass exposure
Exclusion criteria
1. Plans to move within one year 2. Uncontrolled hypertension 3. Pregnancy (assessed by urine pregnancy test among women of childbearing age/menstrual history) 4. Current use of chronic respiratory medications (Long acting Beta 2 Antagonists (LABA), Long-acting muscarinic antagonist (LAMA), inhaled corticosteroid (ICS)) 5. History of post-treatment pulmonary tuberculosis 6. ≥10 pack year tobacco smoking history 7. Known intolerance or contraindication to theophylline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in St. George Respiratory Questionnaire (SGRQ) Scores | Baseline, 1 year | The SGRQ comprises of 50 items and consists of two parts. The first part pertains to symptoms and the second pertains to functional status as well as social and psychological impact of disease. Overall scores ranges between 0 and 100 with higher scores indicating more limitations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Forced Expiratory Volume in One Second (FEV1) | Baseline, 1 year | FEV1 measures how much air a person can exhale during a forced breath. The amount of air exhaled during the first second measured in liters. |
| Change in Forced Vital Capacity (FVC) | Baseline, 1 year | FVC measures how much air a person can exhale at the end of a forced breath measured in liters. |
| Change in St. George Respiratory Questionnaire (SGRQ) Scores | Baseline, 6 months | The SGRQ comprises of 50 items and consists of two parts. The first part pertains to symptoms and the second pertains to functional status as well as social and psychological impact of disease. Overall scores ranges between 0 and 100 with higher scores indicating more limitations. |
Countries
Uganda
Participant flow
Pre-assignment details
There is a discrepancy between the protocol section enrollment number vs the participants that started in the participant flow due to one participant decided not to proceed in the study after they consented and were enrolled but left the study just prior to randomization and therefore did not proceed in the study.
Participants by arm
| Arm | Count |
|---|---|
| Low-dose Theophylline Group Participant in this group will receive low-dose theophylline in addition to standard care, per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment, over a one year period.
Theophylline ER: 200 mg extended release (ER) low-dose theophylline taken orally daily
Standard of Care Treatment: Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment | 50 |
| Placebo Group Participant in this group will receive a placebo in addition to standard care, per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment.
Placebo oral tablet: Manufactured methylcellulose placebo tablet taken orally daily
Standard of Care Treatment: Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment | 49 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 4 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | Low-dose Theophylline Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 19 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 30 Participants | 61 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 49 Participants | 99 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Uganda | 50 participants | 49 participants | 99 participants |
| Sex: Female, Male Female | 30 Participants | 25 Participants | 55 Participants |
| Sex: Female, Male Male | 20 Participants | 24 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 50 | 4 / 49 |
| other Total, other adverse events | 26 / 50 | 19 / 49 |
| serious Total, serious adverse events | 5 / 50 | 3 / 49 |
Outcome results
Primary
Change in St. George Respiratory Questionnaire (SGRQ) Scores
The SGRQ comprises of 50 items and consists of two parts. The first part pertains to symptoms and the second pertains to functional status as well as social and psychological impact of disease. Overall scores ranges between 0 and 100 with higher scores indicating more limitations.
Time frame: Baseline, 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in St. George Respiratory Questionnaire (SGRQ) Scores | 39.02 score on a scale | Standard Deviation 21 |
| Placebo Group | Change in St. George Respiratory Questionnaire (SGRQ) Scores | 45.06 score on a scale | Standard Deviation 16.87 |
Secondary
Change in Forced Expiratory Volume in One Second (FEV1)
FEV1 measures how much air a person can exhale during a forced breath. The amount of air exhaled during the first second measured in liters.
Time frame: Baseline, 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in Forced Expiratory Volume in One Second (FEV1) | 1.40 Liters | Standard Deviation 0.51 |
| Placebo Group | Change in Forced Expiratory Volume in One Second (FEV1) | 1.45 Liters | Standard Deviation 0.58 |
Secondary
Change in Forced Expiratory Volume in One Second (FEV1)
FEV1 measures how much air a person can exhale during a forced breath. The amount of air exhaled during the first second measured in liters.
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in Forced Expiratory Volume in One Second (FEV1) | 1.40 Liters | Standard Deviation 0.51 |
| Placebo Group | Change in Forced Expiratory Volume in One Second (FEV1) | 1.40 Liters | Standard Deviation 0.62 |
Secondary
Change in Forced Vital Capacity (FVC)
FVC measures how much air a person can exhale at the end of a forced breath measured in liters.
Time frame: Baseline, 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in Forced Vital Capacity (FVC) | 2.47 Liters | Standard Deviation 0.68 |
| Placebo Group | Change in Forced Vital Capacity (FVC) | 2.58 Liters | Standard Deviation 0.81 |
Secondary
Change in Forced Vital Capacity (FVC)
FVC measures how much air a person can exhale at the end of a forced breath measured in liters.
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in Forced Vital Capacity (FVC) | 2.51 Liters | Standard Deviation 0.68 |
| Placebo Group | Change in Forced Vital Capacity (FVC) | 2.52 Liters | Standard Deviation 0.84 |
Secondary
Change in St. George Respiratory Questionnaire (SGRQ) Scores
The SGRQ comprises of 50 items and consists of two parts. The first part pertains to symptoms and the second pertains to functional status as well as social and psychological impact of disease. Overall scores ranges between 0 and 100 with higher scores indicating more limitations.
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-dose Theophylline Group | Change in St. George Respiratory Questionnaire (SGRQ) Scores | 37.86 score on a scale | Standard Deviation 21.37 |
| Placebo Group | Change in St. George Respiratory Questionnaire (SGRQ) Scores | 44.45 score on a scale | Standard Deviation 19.48 |