Division of Pulmonary and Critical Care, University of Miami, School of Medicine, Johns Hopkins University, 1951 NW 7th Ave, Suite 2308, Miami, FL, 33136, USA.
Center for Global Non-Communicable Diseases, Johns Hopkins University, Baltimore, USA.
Trials. 2021 Mar 16;22(1):213. doi: 10.1186/s13063-021-05163-2.
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.
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 FEV/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.
ClinicalTrials.gov NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD).
COPD 是全球主要的死亡原因，其大部分发病率和死亡率发生在低收入和中等收入国家（LMIC）。虽然在高收入国家，吸烟是 COPD 的最重要危险因素，但在 LMIC 中，生物燃料烟雾燃烧引起的室内空气污染是 COPD 的主要危险因素。尽管生物燃料相关 COPD 的负担很重，但很少有研究评估这种情况下的药物治疗效果。目前，推荐的 COPD 吸入器疗法在大多数资源有限的环境中既不可用也无法负担。低剂量茶碱是一种口服、每日一次的疗法，长期以来在高收入国家（HIC）使用，在没有吸入性类固醇和/或支气管扩张剂的情况下，已被提议用于治疗 LMIC 的 COPD。低剂量茶碱用于管理与生物燃料相关的 COPD（LODOT-BCOPD）试验研究了低剂量茶碱在管理低收入环境中与生物燃料相关的 COPD 中的临床疗效和成本效益。
LODOT-BCOPD 是一项随机、双盲、安慰剂对照试验，旨在测试低剂量茶碱在改善乌干达中部 110 名中重度 COPD 患者的呼吸症状方面的疗效。纳入标准如下：（1）年龄 40 至 80 岁，（2）为研究地区的全职居民，（3）每日接触生物燃料，（4）支气管扩张剂后 FEV/FVC 低于全球肺倡议混合种族参考人群的第 5 百分位，以及（5）GOLD 分级 B-D COPD。参与者将被随机分配接受每日一次低剂量茶碱（200mg ER，Unicontin-E）或安慰剂治疗 52 周。所有参与者将接受 COPD 自我管理教育和沙丁胺醇急救吸入器。我们将使用圣乔治呼吸问卷（SGRQ）测量健康状况，并在基线和每 6 个月使用 EuroQol-5D（EQ-5D）测量生活质量。此外，我们将在基线、1 个月和 6 个月时评估家庭空气污染水平、血清炎症生物标志物（纤维蛋白原、hs-CRP）和茶碱水平。主要结局是 12 个月时 SGRQ 评分的变化。最后，我们将通过计算 EQ-5D 的质量调整生命年（QALYs）来评估干预措施的成本效益。
ClinicalTrials.gov NCT03984188。于 2019 年 6 月 12 日注册 试验缩写：低剂量茶碱用于管理与生物燃料相关的 COPD（LODOT-BCOPD）。
