Efficacy and safety of a combination herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix for the prophylactic treatment of patients with respiratory tract diseases: a randomised, prospective, double-blind, placebo-controlled phase III trial.

OBJECTIVE

The aim of this ICH-GCP study was to investigate the efficacy and safety of a prophylactic administration of a combination herbal medicinal product (CHMP) in two dosages compared to placebo with respect to the incidence of new occurring infections of the respiratory tract (RTI). Clinical experience of prophylactic treatment of respiratory tract infections with the marketed CHMP containing horseradish root (Armoraciae rusticanae radix) and nasturtium (Tropaeoli majoris herba) has existed for decades.

METHODS

The study was performed as a phase III, multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group trial. All groups received two film coated tablets three times a day. Group 1 received the CHMP tablets 3 × 2 per day, group 2 the CHMP tablets 2 × 2 and placebo tablets 2 × 1 per day and group 3 received placebo tablets 3 × 2 per day. Maximum duration of treatment was 84 days. The primary efficacy criterion was the comparison of the incidences of new occurring RTIs between the treatment groups during the prophylactic treatment. In addition the character of occurring infections, number of sick days and severity of infections were compared. Further criteria were subjects' well being, the satisfaction of subjects with the respective treatments and severity and incidence of the observed adverse events (AE) and serious adverse events (SAE) during the study period.

TRIAL REGISTRATION

EudraCT No. 2010-023227-26.

RESULTS

From 371 subjects screened, a total of 351 subjects of both sexes from 18 to 75 years were randomly allocated to one of the three groups. In order to achieve scientifically and medically impeccable results it was necessary to address acute infections of the respiratory tract occurring during the normal incubation period. Early infections (≤day 7) were excluded from the data set in a sensitivity analysis. In the intention to treat (ITT) population excluding early infections ≤day 7 (n = 344) the infection rates were 13.3% for CHMP 3 × 2 (n = 113), 18.4% for CHMP 2 × 2 (n = 114) and 25.6% for placebo (n = 117). The statistical trend test showed significant results (p = 0.0171). For the per protocol (PP) population - also excluding infections ≤day 7 (n = 334) - infection rates were: CHMP 3 × 2 (n = 110) 12.7%, CHMP 2 × 2 (n = 113) 18.6% and placebo (n = 111) 24.3% (p = 0.0266). Secondary parameters of infections (infection diagnosis, intensity, duration) showed no relevant differences between the treatment groups. The study medication was well tolerated.

LIMITATIONS

This was the first clinical ICH-GCP study with the CHMP conducted in this indication and with a sufficient number of subjects. The study population comprised subjects from 18 to 75 years and covered different diagnoses of RTIs. The results show a benefit when using 3 × 2 film tablets of CHMP for prophylaxis of RTIs. However, no data are available on use of the CHMP in this indication in children, adolescents and the elderly (over 75 years).

CONCLUSION

This trial demonstrates the efficacy and safety of the combination herbal medicinal product as the treatment of first choice in the prophylactic treatment of episodes of respiratory tract infections. Clinical experience was confirmed in an ICH-GCP study.