Reviewed: Jund R, Mondigler M, Steindl H, Stammer H, Stierna P, Bachert C; on behalf of the ARhiSi II study group. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis. Rhinology. December 2012;50(4):417-426.
Acute rhinosinusitis (ARS) refers to the inflammation of the nose and sinuses resulting in symptoms such as nasal discharge, facial pressure and pain, fever, and congestion that persist for less than 10 days. The majority of ARS infections are viral in nature, and botanical supplements may help in alleviating viral ARS. The herbal product Sinupret® extract (referred to in the reviewed paper by its code name, BNO 1016, produced by Bionorica SE; Neumarkt, Germany) contains as active pharmaceutical ingredient a dry extract of a fixed combination of five herbs: gentian (Gentiana lutea, Gentianaceae) root, primula (Primula officinalis, Primulaceae) flower, sorrel (Rumex acetosa, Polygonaceae) herb, European elder (Sambucus nigra, Caprifoliaceae) flower, and verbena (Verbena officinalis, Verbenaceae) herb in a ratio of 1:3:3:3:3. (According to the manufacturer, the composition of herbal raw materials for the production of Sinupret extract is the same as previous Sinupret formulations, which contain a mixture of dried, powdered herbs; a novel process of extracting the active ingredients was employed for Sinupret extract.)
Pharmacological studies have shown Sinupret extract has antiviral, antibacterial, and anti-inflammatory activities. A phase IIb/III clinical trial indicated that the most effective dosage schedule is 160 mg three times daily (tid).1 This randomized, double-blind, placebo-controlled study investigated whether or not 160 mg Sinupret extract tid for 15 days was a safe and efficacious treatment for viral ARS.
The study took place in Germany and enrolled men and women aged 18 to 75 years with a clinical diagnosis of viral ARS defined as sudden onset of at least three of the five main ARS symptoms (i.e., nasal discharge, postnasal drip, congestion, headache, facial pain or pressure) ≤ (equal to or less than) three days prior to enrollment, confirmed by ultrasonography. Included patients had an investigator-evaluated major symptom score (MSS) between eight and 12 (inclusive), with nasal congestion and facial pain or pressure scores between one and two. Exclusion criteria were the use of antibiotics or corticosteroids four weeks before the study or the use of cold medications or immunomodulating drugs seven days before the study. Pregnant or lactating women and people with severe liver, kidney, somatopathic (pertaining to an illness of the body or organ), neurological, and/or psychiatric diseases were excluded as well.
Participants were assigned randomly to take orally either 160 mg tid of the Sinupret extract or placebo for 15 days. Patients recorded the severity of each of the five symptoms, intake of the study medication, and concomitant treatments using diary cards. At the screening visit (day 0) patients were evaluated for eligibility. They returned to the site on days three, seven, 10, and 14 (endpoint), and a follow-up visit took place four weeks (day 28) after the first visit — or earlier if symptoms resolved prematurely. At clinical visits, investigator-evaluated MSS and response to treatment were determined, along with quality of life (as measured by the Sino-Nasal Outcome Test-20 German Adapted Version questionnaire), adverse effects, and treatment compliance (measured by the number of remaining tablets). The sinus ultrasound was repeated at the endpoint and follow-up visit.
The primary endpoint was the investigator-evaluated MSS at end of treatment, and the secondary outcomes included the mean patient-assessed MSS and quality-of-life score, percent of responders, percent of patients dismissed from the study due to antibiotic therapy, percent of patients with ARS detectable by ultrasound at end of treatment, and tolerability. Adverse effects and patient vital signs were recorded at each visit.
A total of 386 patients were allocated randomly, and the intention-to-treat (ITT) total was 380 (n=190 for each group). Over the course of the study, 11 patients were lost to follow-up, 14 dropped out due to lack of efficacy, and 11 needed antibiotics. A total of 86 had relevant protocol deviations. This resulted in a per-protocol total of 300 (n=147 in the treatment group and n=153 in the placebo group). Compliance was 100% in both groups.
At end of treatment, the investigator-evaluated MSS of the Sinupret extract group was significantly less than that of the placebo group (P=0.0008, ITT); this was also true for the secondary outcome of patient-assessed MSS (P=0.0117). Both P values were well below the significance threshold of 0.05. A significantly greater percentage of the herb group (ITT) had an MSS of equal to or less than one as compared to the placebo group (48.4% vs. 35.8%, P=0.0063). Additionally, those with an MSS > 50% of their baseline score were significantly fewer in the herb group (P=0.0099). The number of responders was significantly greater in the herb group at day 10 (P=0.0032) and at day 14 (P=0.0106). Also, the herb group quality-of-life scores were improved by a significantly greater magnitude at all visits (P=0.0019).
Based upon ultrasound analyses, the number of patients with no indication of viral ARS was significantly greater in the Sinupret extract group as compared to the placebo group at the end of the study (P=0.0131). No serious adverse effects were reported. A total of 11.9% of the patients reported adverse side effects such as infections and respiratory or gastrointestinal problems; however, 96.4% of investigators and 94.8% of patients rated the tolerability (safety) of the herbal treatment as “very good” or “good.” The placebo was also rated as “very good” or “good” by 95.3% of investigators and 94.8% of patients.
In this study, the herbal combination product Sinupret extract was well tolerated and provided symptom relief of viral ARS two days earlier than placebo, a significantly greater reduction in MSS, and a significantly greater improvement in quality of life. The authors conclude, “160 mg BNO 1016 tid for two weeks is an efficacious and safe treatment option for the management of patients with acute viral rhinosinusitis; providing a faster and clinically relevant remission of symptoms and improved quality of life, compared with placebo.”
Strengths of this study include the relatively high number of patients and the rigorous study design and analysis. However, there was a pronounced placebo effect; improvements also were observed in the placebo group, but statistical comparisons of endpoint vs. baseline parameters were not reported.
—Amy C. Keller, PhD
- Bachert C, Mondigler M, Steindl H, Stammer H, Stierna P, Eskötter H, Jund R. Multicentre, randomised double-blind, placebo-controlled parallel-group dose-finding study of Herbal Medicine (dry extract) BNO-1016 in acute rhinosinusitis (ARhiSi-1). 84. Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery, Nuremberg, Germany; May 8-12, 2013.