Bruce Barrett, MD, PhD Monica Vohmann, MD Carlo Calabrese, ND, MPH Madison, Wisconsin, and Seattle, Washington Submitted, revised, February 25, 1999. From the Department of Family Medicine, University of Wisconsin-Madison (B.B., M.V.) and Bastyr University, Seattle (C.C.). Requests for reprints should be addressed to Bruce Barrett, MD, PhD, Department of Family Medicine, University of Wisconsin-Madison, 777 S Mills, Madison, WI 53715. E-mail: bbarrett@fammed.wisc.edu.
References
Also recently published, and perhaps most convincing in its reported benefit, was the study by Hoheisel and coworkers66 in 1997. This was a double-blind randomized placebo-controlled single-center clinical trial among adult factory workers in Sweden. The 120 participants were recruited at the first sign of URI, but before a full cold had developed. Participants were randomly given either placebo or active drug, and were followed up until symptoms had resolved. The active drug used was Echinagard, also called Echinacin, a commercial preparation made of juice from the above-ground parts of E purpurea. Participants were instructed to take 20 drops every 2 hours for the first day, and 3 times per day thereafter until symptoms resolved. The authors reported that 60% of the placebo groups, but only 40% of the Echinacea group, developed a “real cold.” Among those who had a “real cold,” the median time to resolution was 4 days in the Echinacea group and 8 days in the placebo group. Statistical significance was reached among all reported outcomes in an intention-to-treat analysis. The limitations of this study include: poorly defined inclusion and exclusion criteria, use of retrospectively defined criteria for progression from “first sign of a cold” to “real cold,”65 and lack of evidence of indistinguishability between Echinacea and placebo.
In their 1992 article, Bräunig and coworkers55 reported the results of a randomized double-blind trial of E purpurea root extract among 180 volunteers presenting with recent-onset influenza-like respiratory symptoms. There were 60 participants in each of the 3 groups: placebo, low-dose, and high-dose. The 2 treatment groups received twice daily doses of either 1 dropperful (about 4.5 mL) or 2 dropperfuls (about 9 mL) of juice extracted from E purpurea root. Primary end points were 8 symptoms (cough, sore throat, nasal symptoms, tearing, headache, fatigue, chills or sweats, and muscle aches) and 1 global indicator of severity, all rated on a 0 to 3 scale as either absent, mild, moderate, or severe, with measurements taken at time 0, after 3 to 4 days, and after 8 to 10 days. Although the low-dose regimen showed little improvement over placebo, the higher-dose group showed statistically significant improvement over placebo in several symptom scores, with positive trends in all measurements. Symptom scores in the treated group were 24% to 50% lower in the placebo group at 3 to 4 days, with the gap widening to 36% to 75% at 8 to 10 days. This study is singular in reporting a dose-dependency effect.
In their 1993 article, Bräunig and colleagues56 described the results of a randomized double-blind clinical trial of E pallida root extract among 160 volunteers presenting with influenza-like respiratory infection. The dose used was equivalent to approximately 900 mg per day of dried extract. Symptom assessment was similar to that described above, with a 4-point none-to-severe rating scale assessed at days 3 to 4 and 8 to 10. The median duration of illness in the Echinacea group was 9.8 days, a statistically significant (P <.001) improvement over placebo (13 days). Interestingly, a physician assessment attempted to classify infections as viral or bacterial. A subgroup analysis showed greater benefit among patients with viral infections. White blood counts and differentials were not clearly different between the placebo and verum groups or the viral and bacterial groups.
Dorn’s57 trial consisted of recruiting 100 participants within 2 days of URI onset, and treating with either placebo or Resistan, a commercial preparation made primarily from E angustifolia herb and root, but also containing extracts from Eupatorium perfoliatum, Baptisia, and Arnica. Dosage was 30 cc for the first and second days, followed by 15 cc on the third through sixth days. Outcomes scored on a 0- to 3-point scale (none, mild, moderate, severe) included 7 self-reported symptoms and several physician-documented signs. These were assessed twice, at days 2 to 4 and 6 to 8. Three symptoms (sore throat, nasal drainage, and cough), and 1 sign (pharyngeal erythema), were reported as significantly superior to placebo (P <.01).
Vorberg and Schneider63 reported a treatment trial in 1989 of Resistan among 100 participants suffering from URI. Patients were enrolled in the first 2 days of URI symptoms and randomly treated with either Resistan or an identical placebo. Symptom scores at days 3 and 8 were significantly improved (P < .01) in the treatment group when compared with placebo, with some benefit found in all assessed symptoms. An approximately 20% benefit at day 3 widened to an average 50% reduction at day 8. The authors concluded that there was a clear severity and duration benefit to Echinacea when compared with placebo.
