Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD

University of Miami

Status and phase: Completed; Phase 3

Conditions: Pollution; Exposure; COPD Exacerbation Acute; COPD; Pollution Related Respiratory Disorder; COPD Exacerbation

Treatments: Drug: Placebo oral tablet; Drug: Theophylline ER; Other: Standard of Care Treatment

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03984188

1K23HL146946-01 (U.S. NIH Grant/Contract)

IRB00209008 (Other Identifier)

20201523

Details and patient eligibility

About

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.

Enrollment: 100 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

Low-dose Theophylline Group

Experimental group

Description:

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.

Treatment:

Other: Standard of Care Treatment

Drug: Theophylline ER

Placebo Group

Placebo Comparator group

Description:

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.

Treatment:

Other: Standard of Care Treatment

Drug: Placebo oral tablet