Thursday, 24 September 2015

Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

Volume 77, December 2015, Pages 66–72

Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

Under a Creative Commons license
  Open Access



Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu.


This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza.


Following informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea-based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (2-sided) and using a CI approach in the per-protocol sample.


Recovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487–0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink.


Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self-care. Clinical trial identifier: Eudra-CT: 2010-021571-88. (Curr Ther Res Clin Exp. 2015; 77:66–72)

Key words

  • Complications;
  • echinacea;
  • influenza;
  • noninferiority;
  • oseltamivir;
  • recovery


Influenza presents a potential threat to human beings with seasonal epidemics and occasional severe pandemics, following reassortment of viral antigens. The World Health Organization estimates a total of 25 to 50 million cases each year resulting in 150,000 hospitalizations and 30,000 to 40,000 deaths in the United States alone, due to epidemic influenza. During pandemics the mortality and morbidity may be much higher, putting enormous pressure on basic health service provisions.[1] and [2]
Influenza illness is characterized by involvement of the lower respiratory tract (cough) accompanied with systemic complaints, including headache, myalgia, and fever.[3] and [4] Acute onset of cough and fever are good clinical predictors, associated with positive tests for influenza virus in 79% to 88% of patients during acute epidemics. Results depend to a large extent on detection and sampling methods as well as the severity of epidemic.[5] and [6] Influenza viruses replicate predominantly in the airway epithelia, but also in various other host organs and tissues leading to airway congestion, inflammation, and necrosis.7 Complications are frequent and severe complications include encephalitis, myelitis, myocarditis, intravascular coagulation, and septic shock.[8] and [9] Patients with underlying respiratory or cardiovascular disorders, children, older adults, and immunocompromised individuals display higher rates of severe illness and mortality.10 Overall, acute respiratory tract infections severely influence morbidity and mortality during the winter and influenza plays a central role in this context.[11] and [12]
Neuraminidase inhibitors are recommended for the early treatment of influenza by the Centers for Disease Control and Prevention, the German Gesellschaft für Virologie, and the UK National Institute for Health and Care Excellence (NICE). The neuraminidase inhibitors oseltamivir and zanamivir have been demonstrated to reduce the duration and intensity of illness, but early intervention appears critical.[13] and [14] Success of therapy depends on the sensitivity of causative viruses to these drugs. During the 2008–2009 winter season most seasonal H1N1 influenza subtypes had developed reduced sensitivity to oseltamivir. In subsequent years this resistant virus type was again replaced by more sensitive strains like H1N1pdm2009 or H3N2.15 Neuraminidase inhibitors are associated with adverse effects, including nausea, vomiting, psychiatric effects, and renal events. Safety issues, the importance of early administration, availability, and the potential emergence of resistance compromise the broad applicability of neuraminidase inhibitors as recently highlighted by Jefferson et al.16
Antiviral activities are found in plants, including echinacea. A hydroethanolic extract prepared from freshly harvested Echinacea purpurea has demonstrated strong activity against a series of influenza viruses (eg, H1N1, H3N2, H5N1, H7N7, and H1N1pdm2009). [17] and [18] The extract exhibited no potential to induce resistance and inactivated oseltamivir-resistant H5N1 influenza viruses. In addition to the direct inhibition of influenza viruses, anti-inflammatory activities and modulation of the immune system may contribute to echinacea’s pharmacologic spectrum. [19] and [20]
We tested efficacy and safety of a newly developed preparation of Echinacea purpurea called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil Switzerland) for the treatment of acute influenza symptoms compared with the neuraminidase inhibitor oseltamivir. [13] and [14] Patients with clinically diagnosed influenza were recruited as early as possible after symptom onset. The inclusion criteria were matched with those for which the comparator had demonstrated superior over placebo treatment in previous trials. The inclusion period corresponded with the circulation period of influenza viruses in the community. Nasal swab virus testing further enhanced diagnostic specificity.