Treating acute exacerbations of COPD with Chinese herbal medicine to aid antibiotic use reduction (Excalibur): a randomised double-blind, placebo-controlled feasibility trial

Abstract

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine “Shufeng Jiedu” (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD.Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care.Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis.Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from “rescue packs” before seeing their GP, and workforce challenges in primary care.Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients’ “rescue packs” and delegating recruitment to a central trials team.Clinical Trial Registration: Identifier, ISRCTN26614726

Editorial: Clinical phytopharmacology

“…However, progress has slowed down since the COVID-19 pandemic, as many trials were postponed. The increased use of remote consultations also made recruitment more difficult for trials which require face-to-face clinical assessment ( Willcox et al, 2023 ). This might explain why this special Research Topic had relatively few submissions.…”

“…However, a feasibility trial can be very useful to determine the acceptability of the herbal preparation in patient groups who are not accustomed to taking it, and the feasibility of delivering it in different ways. For example, what would conventional medical doctors in the United Kingdom feel about giving a herbal medicine, and how many of their patients would accept this instead of, or as well as, conventional treatment ( Flower et al, 2019 ; Soilemezi et al, 2020 ; Willcox et al, 2021a ; Willcox et al, 2023 )? The feasibility trial also helps to identify important challenges in recruiting patients, follow-up, collecting and prioritising outcome measures, which can greatly improve the development of a definitive trial protocol ( Willcox et al, 2021a ; Willcox et al, 2023 ).…”

“…For example, what would conventional medical doctors in the United Kingdom feel about giving a herbal medicine, and how many of their patients would accept this instead of, or as well as, conventional treatment ( Flower et al, 2019 ; Soilemezi et al, 2020 ; Willcox et al, 2021a ; Willcox et al, 2023 )? The feasibility trial also helps to identify important challenges in recruiting patients, follow-up, collecting and prioritising outcome measures, which can greatly improve the development of a definitive trial protocol ( Willcox et al, 2021a ; Willcox et al, 2023 ). However, moving from a feasibility trial to a definitive trial has also been challenging in recent years.…”