Trials (Mar 2021)

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

DOI
https://doi.org/10.1186/s13063-021-05163-2
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 9

Abstract

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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)

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