Efficacy and Tolerability of Myrtol Standardized in Acute Bronchitis - A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol

Myrtol standardized (Gelomyrtol(R) forte) is a phytotherapeutic extract (di stillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limon ene and 1,8-cineole. Objective: This study describes and compares the efficacy, safety and toler ability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), ce furoxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 186 83-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched place bo in acute bronchitis. Patients: 676 male and female outpatients, aged greater than or equal to 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75 % of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study. Intervention: Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 16 3) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of tre atment (visits 2 and 3) and at 2 weeks after conclusion of the treatments ( visit 4). Criteria: Responder- and non-responder rates (primary), signs (abnormal aus cultation), symptoms (daily diary data on nightly cough, coughing fits duri ng the day, sputum consistence and general well-being; visit data on bronch ial hyperreactivity and absence/presence of associated symptoms), FEV1, ove rall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were e valuated for the intention-to-treat data-set (ITT) and the 'efficacy evalua ble' sample (EAP), i.e. excluding patients with missing values (incl. disco ntinued non-responders and drop-outs for other reasons) at the time of asse ssment. Results: The signs and symptoms of acute bronchitis regressed readily in al l treatment groups, but regression was slower and less complete in the pati ents treated with placebo. In patients treated with placebo, the acute bron chitis was considered to have deteriorated to such an extent that discontin uation was indicated ('non-responder') in 36 patients (ITT: 20.9 %, 95 % CI : 15.1 to 27.8 % and EAP: 21.3 %, CI: 15.4 to 28.3 %) after 1 week (visit 2 ) and in 19 further patients (ITT: 11.0 %, CI: 6.8 to 16.7 %; EAP: 14.8 %, CI: 9.2 to 22.2 %) after 1 further week (visit 3). In contrast, in the grou p of patients treated with myrtol stand. the non-re-spender rates at visits 2 and 3 were only 5.3 % (ITT, CI: 2.4 to 9.8 %; EAP: 5.4 %, CI: 2.5 to 10. 0 %) and 1.2 % (ITT, CI: 0.1 to 4.2 %; EAP: 1.3 %, CI: 0.2 to 4.7 %); the r esponder rates at visit 2 were statistically significantly higher (p < 0.00 1) for myrtol stand. (ITT: 92.9 %, CI: 88.0 to 96.3) compared to placebo (I TT: 77.3 %, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92 .4 %, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6 %, CI: 83.8 to 93.8 %). The superiority of the active treatments vs. placebo with little difference am ong the treatments was confirmed for all further criteria of evaluation. Th ere was no evidence of bronchoconstriction or relapse in any treatment grou p for the patients continuing treatment (i.e. for those who were not discon tinued because of non-response). The treatments were safe and comparably we ll tolerated. Conclusion: Compared to placebo, treatment with myrtol stand. was well tole rated but evidently superior in terms of efficacy, resulting in a more rapi d and more complete recovery; although well comparable with the other activ e treatments, myrtol stand. tended to be superior to cefuroxime and ambroxo l for several ancillary criteria. Myrtol stand. is a well-evidenced alterna tive to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.