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

NCT ID: NCT03984188

Last Updated: 2024-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-23
• Study Completion Date: 2023-12-15

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Theophylline ER

Intervention Type: DRUG

200 mg extended release (ER) low-dose theophylline taken orally daily

Standard of Care Treatment

Intervention Type: OTHER

Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Manufactured methylcellulose placebo tablet taken orally daily

Standard of Care Treatment

Intervention Type: OTHER

Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment

Interventions

Theophylline ER

200 mg extended release (ER) low-dose theophylline taken orally daily

Intervention Type: DRUG

Placebo oral tablet

Manufactured methylcellulose placebo tablet taken orally daily

Intervention Type: DRUG

Standard of Care Treatment

Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment

Intervention Type: OTHER

Other Intervention Names

Low-dose Theophylline

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Trishul Siddharthan

Assistant Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Trishul Siddharthan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

Makerere Lung Institute

Kampala, , Uganda

Nakaseke Hospital

Nakaseke, , Uganda

Countries

Uganda

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: DERIVED

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1K23HL146946-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00209008

Identifier Type: OTHER

Identifier Source: secondary_id

20201523

Identifier Type: -

Identifier Source: org_study_id