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Three Part Question

For [patients with suspected or proven influenza], do [products containing Echinacea Purpurea extract] reduce their [clinical symptoms or duration of illness] compared to [placebo or Oseltamivir]?

Clinical Scenario

You are working in an Emergency Department during the Influenza season. You see a patient who has presented with typical symptoms of influenza. Their point of care influenza test is positive, but they don’t have ‘high risk’ clinical features making Oseltamivir (Tamiflu) an appropriate option. You wonder whether, for [patients with suspected or proven influenza], whether [products containing Echinacea Purpurea extract] might reduce the [clinical symptoms or duration of illness] compared to [placebo or Oseltamivir].

Search Strategy

Search of Medline Ultimate on 30/12/02023
Using ‘Echinacea’ AND ‘influenza’ as search terms limited to the abstracts

Search Outcome

The search returned 32 articles, of which one directly answered the clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Rauš K et al 20/04/2015 Czech Republic	472 patients with symptoms of influenza for <48 hours randomised to 5 days of oseltamivir followed by 5 days of placebo or 10 days of Echinaforce Hotdrink. Double blind and fully placebo controlled. Patients were recruited whilst there were high circulating influenza levels in the population. A small number of children were included. Pregnant patients, smokers, and those with an extensive range of medical diagnoses were excluded Non-inferiority was demonstrated for Echinaforce for symptomatic recovery at 1, 5 and 10 days 41 patients had virologically confirmed influenza. Non inferiority of Echinaforce demonstrated for these patients. The proportion of these patients who were symptom free at 10 days was 95% in the Echinaforce group and 76% in the Oseltamivir group, which was noted to be statistically significant Fewer side effects and complications of influenza were reported with Echinaforce Patients recruited in Primary Care might not reflect the patient population in our EDs The Echinaforce preparation also includes some elderberry extract, which isn’t included in many Echinachea preparations available in the UK	Multicentre, randomised, double blind, placebo controlled trial comparing 5 days of oseltamivir followed by 5 days of placebo capsules, plus placebo drink, or 10 days of Echinaforce Hotdrink and placebo capsules	Non-inferiority	demonstrated for Echinaforce for symptomatic recovery at 1, 5 and 10 days	Patients recruited in Primary Care might not reflect the patient population in our EDs The Echinaforce preparation also includes some elderberry extract, which isn’t included in many Echinachea preparations available in the UK
			41 patients had virologically confirmed influenza. Non inferiority of Echinaforce	demonstrated for these patients. The proportion of these patients who were symptom free at 10 days was 95% in the Echinaforce group and 76% in the Oseltamivir group, which was noted to be statistically significant
			Side effects	Fewer side effects and complications of influenza were reported with Echinaforce

Comment(s)

The American Purple Coneflower, Echinacea Purpura, has been used by the indigenous peoples of North America to treat upper respiratory tract infections long before the introduction of European medicines [1]. The study by Raus and colleagues was the only trial of an Echinacea product for patients with suspected or confirmed influenza identified by this search. They recruited their patients from 29 General Practices around Prague in the Czech Republic. This was a non-inferiority trial comparing Echinaforce with Oseltamivir. Patients in this study were also allowed to take paracetamol and dextromethorphan. The authors reported that the blinding was effective, with most patients having no idea which arm they were in. The study wasn’t designed to test whether Echinaforce was superior to Oseltamivir, but results showed that patients treated with Echinaforce had fewer side effects and more patients with confirmed influenza had recovered by day 10. It would be helpful to know whether the patients in the two groups with confirmed influenza were similar at baseline before concluding it was probably a causal relationship. This study used Oseltamivir as being the best standard treatment for patients with influenza. However, it excluded most ‘higher risk’ patients for whom NICE recommends Oseltamivir [2]. A Cochrane review of Oseltamivir reported that Oseltamivir does have a modest effect in unselected adults, reducing the duration of the illness by 16.8 hours, but it can cause nausea and vomiting [3]. The authors of the Cochrane review noted that, in the studies they reviewed, Oseltamivir had a smaller number needed to harm than the number needed to treat. Having an alternative treatment option with fewer side effects for ‘lower risk’ patients with influenza is an attractive one. Echinacea isn’t listed in the BNF but Echinacea products such as Echinaforce are available to buy over the counter in the UK.

Clinical Bottom Line

For selected low risk patients with suspected or confirmed influenza presenting within 48 hours of symptom onset, recommending Echinaforce in addition to standard supportive treatment may reduce the duration of illness and appears to be safe.

References

1. Rauš K, Pleschka S, Klein P et al. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial Curr Ther Res Clin Exp 2015; 77: 66-72. doi: 10.1016/j.curtheres.2015.04.001.
2. Hudson JB. Applications of the phytomedicine Echinacea purpurea (Purple Coneflower) in infectious diseases. J Biomed Biotechnol. 2012;2012:769896. doi: 10.1155/2012/769896.
3. NICE https://www.nice.org.uk/guidance/ta168/resources/oseltamivir-zanamivir-and-amantadine-for-the-treatment-of-influenza-pdf-376420573 (accessed 30/12/2023) [Online]
4. Jefferson T, Jones MA, Doshi P et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD008965. DOI: 10.1002/14651858.CD0