Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial

Trishul Siddharthan, Suzanne L Pollard, Peter Jackson, Nicole M Robertson, Adaeze C Wosu, Nihaal Rahman, Roma Padalkar, Isaac Sekitoleko, Esther Namazzi, Patricia Alupo, John R Hurst, Robert Kalyesubula, David Dowdy, Robert Wise, Peter J Barnes, William Checkley, Bruce Kirenga, Trishul Siddharthan, Suzanne L Pollard, Peter Jackson, Nicole M Robertson, Adaeze C Wosu, Nihaal Rahman, Roma Padalkar, Isaac Sekitoleko, Esther Namazzi, Patricia Alupo, John R Hurst, Robert Kalyesubula, David Dowdy, Robert Wise, Peter J Barnes, William Checkley, Bruce Kirenga

Abstract

Background: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting.

Methods: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D.

Trial registration: ClinicalTrials.gov NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD).

Keywords: Biomass; COPD; Theophylline.

Conflict of interest statement

The authors declare they have no competing interests.

Figures

Fig. 1
Fig. 1
Recruitment diagram
Fig. 2
Fig. 2
Schedule of enrollment, interventions and assessments
Fig. 3
Fig. 3
Schedule of enrollment, interventions, and assessments for participants

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