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
Abstract
Background
Echinacea
has antiviral activity against influenza viruses in vitro and has
traditionally been used for treatment of colds and flu.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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
Introduction
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.
