Clinical Research

In the UK, Wilcox et al (2021) undertook a feasibility double blind randomised placebo-controlled trial in primary care for the treatment of acute bronchitis, the HATRIC trial. The primary purpose of the trial was to assess the feasibility of conducting a RCT of Pelargonium treatment in general practices (primary care). From 20 GP practices, 134 patients were randomised to receive Pelargonium or placebo after consultation with the doctor or practice nurse. It was a cluster randomised trial so practices gave out all liquid or all tablet preparations. Participants were provided with and asked to complete a study diary for four weeks. GPs were allowed to prescribe antibiotics as per their practice policy; no antibiotics, immediate antibiotics or delayed antibiotic prescription. Quality of life was assessed using the EQ-5D-5L questionnaire. A nested qualitative study of 29 patients and 11 healthcare professionals was also undertaken.

Although the trial was not powered to detect differences in outcomes of symptoms between the groups, the authors did report faster recovery in the treatment groups compared to placebo. Key outcome measures were obtained for 80% of participants. The recruitment rate was faster than predicted. The authors concluded that progression to a phase III trial was feasible. A significant improvement in the study design was suggested to start the herbal medicine sooner when symptoms first appear; using pharmacies for this could be an option.

A nested qualitative study (HATRIC-Q) was undertaken alongside, the results of which have been published by Soilemezi et al (2020). The views of 29 patients and 11 healthcare professionals on the use of herbal medicines were explored. There was concern among the patient group that herbal medicines are not effective or as quick to relieve symptoms as antibiotics but there was a willingness to try them if their GP recommended them. There was divided opinion regarding side-effects, some patients perceiving them as natural with fewer side effects but others were concerned about potential side effects.

Clinicians expressed a need for evidence, clinical guidelines and training and that herbal medicines were not in their area of expertise.

A multicentre observational post-marketing surveillance study was reported by Haidvogl and Heger (2007). From 158 centres, a total of 742 children aged 0 to 12 years with acute bronchitis or acute exacerbations of chronic bronchitis were enrolled. Just over half (51.8%) too no further medication; of those that did it was mainly antitussive agents and expectorants, rhinilogical or broncholytic agents. The BSS dropped from 6.0 (±3.0) points at baseline to 2.7 (±2.5) at one week and to 1.4 (±2.1) at the end of the study. Complete or partial remission was achieved in 90.2% of children.

Tolerability was rated (bay physician, parents and patients) as good or very good in 94.9% of cases. There were 13 adverse events reported described as mild to moderate; eight of which a causal relation with the test medication could not be excluded. Subsequent treatment with antibiotics was required for two patients

Most of the trials of Pelargonium to treat the common cold have been included in the systematic reviews summarised elsewhere on this website.

When new studies are published they will appear here.

Bachert et al (2009) reported their RCT of the treatment of rhinosinusitis using Pelargonium vs placebo. Sinus involvement was confirmed with occipitomental radiographs. The infection was presumed to be bacterial in origin. A total of 103 patients (51 treatment, 52 placebo) were treated and analysed in the intention to treat analysis (ITT). The primary outcome was reduction in sinusitis severity score (SSS) at day seven. There was a 5.5 point reduction in the SSS for those treated with Pelargonium compared to 2.5 points with placebo (p<0.0001). Radiographically there was significant improvement of the maxillary sinuses in the treatment group with clear but not significant tendencies in the ethmoid and frontal sinuses.

Perić et al (2020) undertook a non-inferiority open label randomised trial comparing Pelargonium with Amoxicillin for acute bacterial rhinosinusitis. There were 50 patients randomised, 25 in each group. Total symptom score (TSS), individual symptoms scores, total endoscopic score and individual endoscopic signs before and after treatment were the outcome measures. Additionally, endoscopic aspirates for microbiological cultures were obtained.

There was higher absolute improvement for TSS, nasal obstruction, facial pain, impaired sense of smell, TES, mucosal oedema, and mucopurulent secretion in the Pelargonium compared to the amoxicillin group. From day 7 of treatment TSS was significantly improved in the Pelargonium group compared the the antibiotic group (p<0.001). Also, fewer bacteria grew on culture in the Pelargonium group compared to the amoxicillin group.

The same group also published an observational study (Perić et al, 2020) that examined the levels of 13 inflammatory chemokines in the nasal secretions of patients with acute post-viral rhinosinusitis before and after treatment with Pelargonium compared to normal controls. After Pelargonium treatment there was an increase in production of some chemokines including ones which are chemoattractive for monocytes, macrophages, T-cells and natural killer cells. Conversely, there was a reduction in neutrophil chemokines. The authors suggest that this leads to lower production of neutrophil proteases which results in better protection and stabilisation of the respiratory epithelium.

Martin et al (2020) tested the hypothesis that the prescription of phytopharmaceuticals to treat respiratory tract infections was associated with lower antibiotic use. A case-control methodology was used; 117,182 patients who received a phytopharmaceutical were matched with the same number of controls. The diagnoses included nasopharyngitis, sinusitis, pharyngitis, bronchitis and acute upper respiratory infections of multiple and unspecified sites. Numerous phytochemicals were prescribed including thyme and primrose root extracts, extract of dry gentian root, primrose flower, sorrel, elderflower and verbena, dry ivy leaf extract, cineole and Pelargonium sidoides root extract. Pelargonium was significantly associated with reduced antibiotic prescribing by general practitioners (Odds ratio 0.49, 95% CI 0.43  - 0.57) and paediatricians (OR 0.57 [0.38 - 0.84]) despite being one of the least often prescribed phytopharmaceuticals. It was also associated with few days of sick leave.

Having just finished his residency, Dr Robert Centor was looking for which clinical findings could stratify the probability that an adult with a sore throat had a group A Streptococcal infection. On a cohort of 234 patients, a predictive model was developed narrowing down from 14 potential predictors to just four. A score of 4 had a 56% probability of being Strep A positive culture.

The four variables are:

1. Exudate or swelling of the tonsils
2. Tender and/or swollen anterior cervical lymph nodes
3. Temperature above 38 degrees centigrade
4. Absence of a cough

Each positive criteria scores one point up to a maximum of four. The probabilities of a culture positive for Group A Strep in the study by Centor et al (1981) were as follows

Guidelines recommend when there is a likelihood of group A Strep infection in patients with a Centor score of 3 or 4 that doctors should consider a rapid antigen test. If group A Strep infection is confirmed then antibiotics may be indicated. Sore throat test and treat services are not currently routine in the UK but pharmacy-based feasibility studies have reported promising results and reduce pressures for other primary care providers.

Bereznoy et al (2003) reported their randomised double-blind placebo controlled trial of Pelargonium for the treatment of tonsillopharyngitis. One hundred and forty four patients aged 6 -10 years with non-group A beta haemolytic streptococcus tonisllopharyngitis were randomised to either Pelargonium or placebo. The primary outcome was decrease in the Tonsillopharyngitis Severity Score (TSS) from day ) to day 4. In the Pelargonium treatment group the decrease in TSS at day 4 was 7.1 ± 2.1 points compared to 2.5 ± 3.6 points for the placebo which was significant (p<0.00001). Unsurprisingly, there were significant differences between the two groups in the secondary outcomes including rapid recovery, individual symptoms (headache, sore throat, fever and sore throat) and ability to undertake activity. No adverse events were attributed to the investigational medication but adverse events related to the infection did cause more drop outs in the placebo group because of lack of efficacy.

In a trial conducted before the Covid-19 pandemic Keck et al (2021) reported that Pelargonium treatment was favourable in patients with common cold symptoms over a third of whom were human coronavirus positive nucleic acid positive (HCoV-HKU1, HCoV-OC43, HCoV-NL63 & HCoV-229E).

Emanuel et al (2023) reported the in vitro and in vivo (in hamsters) effects of Pelargonium root extract against SARS-CoV-2 and some of its variants.

There are no current clinical trails in humans reported but literature reviews and in silico simulations suggest Pelargonium could possibly work against SARS-CoV-2.