Reviewed: Popovych V, Koshel I, Malofiichuk A, et al. A randomized, open-label, multicenter, comparative study of therapeutic efficacy, safety and tolerability of BNO 1030 extract, containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years. Am J Otolaryngol. March-April 2019;40(2):265-273. doi: 10.1016/j.amjoto.2018.10.012.
Symptoms of acute tonsillitis include sore throat with or without trouble swallowing, hyperemia (excessive blood flow in vessels at an organ site), enlargement of the tonsils with potential presence of plaque, enlargement of cervical lymph nodes, fever, and general weakness. Most cases (70%-95%) are caused by viral infections, which are treated symptomatically with acetaminophen or ibuprofen.
The standardized herbal combination product Imupret® (Bionorica SE; Neumarkt, Germany) has demonstrated antiviral, anti-inflammatory, and immunomodulatory properties. Imupret is an official medication (oral drops) sold in pharmacies in Germany, Estonia, Latvia, Lithuania, Poland, Ukraine, and 12 other countries (though not currently available in the United States) and is used to treat upper respiratory tract diseases and prevent complications and recurrences of respiratory viral infections.
Every 100 g of Imupret contains 29 g of the standardized aqueous-alcohol (59% ethanol v/v) extract BNO 1030 produced from 0.4 g marshmallow (Althaea officinalis, Malvaceae) root, 0.3 g chamomile (Matricaria recutita syn. M. chamomilla, Asteraceae) flowers, 0.5 g horsetail (Equisetum arvense, Equisetaceae) herb, 0.4 g walnut (Juglans regia, Juglandaceae) leaves, 0.4 g yarrow (Achillea millefolium, Asteraceae) herb, 0.2 g oak (Quercus spp., Fagaceae) bark, and 0.4 g dandelion (Taraxacum officinale, Asteraceae) herb.
The authors conducted a randomized, open-label, parallel-group study to assess the efficacy and safety of Imupret compared with standard therapy for treating the symptoms of acute non-bacterial tonsillitis. The study was conducted in six outpatient institutions in Ukraine from June 2017 to March 2018.
The study included male and female patients aged six to 18 years, who were undergoing outpatient therapy with a diagnosis of acute non-bacterial tonsillitis and were able to start treatment within 72 hours of symptom onset. Included patients had a score of −1 to 3 points on the McIsaac Scale (used for patients aged six to 14 years) or 0 to 2 points on the Centor Score (used for patients over 15 years old), which indicates a “high probability of viral tonsillitis.”
Excluded patients had a McIsaac Scale score > 3; a Centor Score > 2; indications for immediate commencement of systemic antibiotic therapy; suspected infectious mononucleosis; intolerability or individual hypersensitivity to any ingredient of the treatment; or used systemic antibacterial or antifungal agents, systemic glucocorticosteroids, or cytostatics within the two weeks before the start of the study. Patient withdrawal criteria were: withdrawal of written informed consent; loss of contact with a patient; intolerability of the study drug or the reference treatment; development of serious and/or unexpected adverse effects (AEs); considerable worsening of general condition; development of underlying disease complications; violation of protocol; and prescription of systemic antibiotic therapy.
Of the 238 patients, 118 (52 males and 66 females) received Imupret plus standard treatment and 120 (62 males and 58 females) received standard treatment only. Standard treatment included acetaminophen to reduce fever, benzydamine hydrochloride nasal spray (a nonsteroidal anti-inflammatory drug), a sparing diet, and elimination of chemical and environmental irritants. In the Imupret group, patients aged 12 years and older took 25 Imupret drops six times daily for 10 days, and patients aged six to 11 years took 15 drops six times daily for the first five days and 15 drops three times daily on days six to 10.
All patients were assessed at baseline, at 36 to 48 hours, on day 5 ± 1, and on day 10 ± 1. At each visit, a physician assessed the patient’s general condition using a 10-point visual analog scale (VAS) and the severity of six tonsillitis symptoms (rating each on a four-point scale): hyperemia of posterior pharyngeal wall, hyperemia of tonsils, swelling and plaque on tonsils, sore throat at rest, sore throat while swallowing, and throat irritation associated with cough. In addition, patients or their parent/guardian completed a daily diary assessing the severity of each symptom on a 10-point VAS. Secondary outcome measures were decrease in total symptom score, antipyretic use, and calculated therapeutic benefit in terms of illness duration.
There were no significant differences between groups at baseline. The mean age of the patients was 9.16 years. Four patients in the Imupret group and 10 in the control group had to withdraw from the study because they were prescribed antibiotics.
At days 5 and 10, the Imupret group had a significantly greater reduction in the severity of sore throat when swallowing and sore throat at rest (the “main tonsillitis manifestations”) compared to the control group (P < 0.05 for both). Based on the patient diary data, the improvement of these symptoms was significantly greater in the Imupret group from day 2 to day 10 compared to the control group (P < 0.05 for both). At day 5, the Imupret group reported greater improvement in throat irritation associated with cough compared with the control group (P < 0.05). However, no significant differences in the severity of this symptom were observed after day 5.
The physician assessments indicated significantly greater improvement of the general condition in the Imupret group compared with the control group at days 5 and 10 (P < 0.05 for both). The patient/parent/guardian assessments of general condition showed greater improvement from day 2 to day 10 in the Imupret group compared to placebo (P < 0.05). By day 10, 81.6% of patients in the Imupret group and 65.4% of patients in the control group were classified as treatment responders (P < 0.036). The authors defined a treatment response as a decrease in the total score of the main tonsillitis manifestations to 4 or lower. From day 4 until the end of the study, fewer patients in the Imupret group used antipyretics compared with the control group (P < 0.05). The “therapeutic benefit” of Imupret was 4.2 days. The authors calculated the therapeutic benefit by taking the average general condition score of the control group on day 10 (2.72) and comparing it to the day the treatment group reached that score (4.2 days earlier). Imupret was well-tolerated, and no AEs were reported.
In summary, the supplemental use of Imupret to treat acute non-bacterial tonsillitis in children was associated with improved clinical symptoms, improved general condition and quality of life, decreased use of antipyretics, and shortened illness duration. Although not statistically significant, a trend toward reduced prescription of antibiotics in the Imupret group was observed.
According to the authors, major limitations of the study were the lack of blinding and a placebo plus standard care treatment arm and the lack of controls for the use of other herbal medicinal products or treatments such as medicated lozenges.
The authors conclude “BNO 1030 (Imupret®) is a safe and effective product for treatment of acute non-bacterial tonsillitis in children aged 6–18 years, assuring therapeutic benefit when prescribed additionally to the standard symptomatic therapy.”