Pelargonium sidoides root extract for the treatment of acute cough due to lower respiratory tract infection in adults: a feasibility double-blind, placebo-controlled randomised trial

Abstract

Background Pelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or “Kaloba®”, is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries. Study design Feasibility double-blind randomised placebo-controlled clinical trial. Methods We aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2–4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial. Results Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex. Conclusions It was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition. Trial registration HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884.

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

“…Although there have been many trials of herbal medicine for AECOPD in China, this is the first in the UK, where the population is much less accustomed to using herbal remedies. Nevertheless, our findings confirm results of previous research in acute bronchitis and other acute respiratory infections, which showed that most patients and clinicians are willing to try herbal alternatives to antibiotics ( Soilemezi et al, 2020 ; Willcox et al, 2020 ; Willcox et al, 2021 ).…”

Common cold

“…A wide range of herbal medicines and plant based chemicals such as iota-carrageenan and menthol are recommended for prevention and treatment of the common cold. Echinacea and Pelargonium are two of the most popular herbal treatments and they have support for efficacy from clinical trials on common cold ( 78 – 81 ) although the clinical relevance of the efficacy has been reported as questionable ( 82 ). Iota-carrageenan has been studied several clinical trials on common cold and there are claims that it is an effective anti-viral medicine ( 83 , 84 ).…”

Editorial: Clinical phytopharmacology

“…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.…”

“…Close collaboration with the herbal manufacturer is essential for this ( Flower et al, 2019 ). Nevertheless, many patients do not know what taste to expect, so inert colouring and flavouring can be enough to mimic a “herbal” preparation and produce effective blinding for both patients and researchers ( Willcox et al, 2021a ). Apart from the herbal medicine being tested, the groups should receive identical treatment and outcomes should be measured in the same way, using valid and reliable measures.…”