TY - JOUR
T1 - Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD)
T2 - study protocol for a randomized controlled trial
AU - Siddharthan, Trishul
AU - Pollard, Suzanne L.
AU - Jackson, Peter
AU - Robertson, Nicole M.
AU - Wosu, Adaeze C.
AU - Rahman, Nihaal
AU - Padalkar, Roma
AU - Sekitoleko, Isaac
AU - Namazzi, Esther
AU - Alupo, Patricia
AU - Hurst, John R.
AU - Kalyesubula, Robert
AU - Dowdy, David
AU - Wise, Robert
AU - Barnes, Peter J.
AU - Checkley, William
AU - Kirenga, Bruce
N1 - Funding Information:
This study is funded by the National Institutes of Health (NHLBI/NIH). Peer review of the original grant application contributed to the final study design. A representative of the funder may attend DSMB meetings, though the funder otherwise has no role in the conduct or analyses of the study.
Funding Information:
This study was funded by a Mentored Career Development Award through the National Heart, Lung and Blood Institute of the National Institutes of Health (K23 HL146946/HL/NHLBI). The funding agency has no role in the design of the study and collection, analysis and interpretation of data, and in writing the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Biomass
KW - COPD
KW - Theophylline
UR - http://www.scopus.com/inward/record.url?scp=85102687832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102687832&partnerID=8YFLogxK
U2 - 10.1186/s13063-021-05163-2
DO - 10.1186/s13063-021-05163-2
M3 - Article
C2 - 33726828
AN - SCOPUS:85102687832
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 213
ER -