[Rengalin, a New Efficacious and Safe Antitussive Agent. Results of a Randomized, Comparative, Multicenter Clinical Trial in Patients with Acute Respiratory Tract Infections].

Abstract

Unlabelled: Rengalin is a release-active combination antitussive drug based on antibodies to bradykinin, to histamine and morphine. It acts at various mechanisms of cough reflex by modifying endogenous target molecules and their interaction with receptors. The drug's efficacy, as demonstrated previously in experimental and clinical studies, is mediated by specific release-activity obtained as a result of the production process.

Methods: Efficacy and safety assessment of rengalin in the treatment of cough induced by acute upper respiratory tract infections (URIs) in comparison with a complex codeine-containing drug (codelac) was performed as part of a multicenter, randomized clinical trial involving 143 patients. All the participants presented with dry/non-productive cough caused by URIs (pharyngitis, laryngitis, tracheitis, tracheobronchitis, bronchitis). The duration of cough varied between 12 hours and 7 days. Rengalin was administered in 73 patients receiving 2 tablets 3 times daily for initial three days, and half reduced doses--for the subsequent four days; codelac was administered in 70 patients who were given 1 tablet 3 times daily for the entire treatment period (7 days). Primary efficacy endpoints were time to cough resolution and reduction in the severity of the cough (scored using a Cough Severity Scale). One patient in Rengalin group and three patients in Codelac group were withdrawn from the study. The article presents treatment outcomes obtained for 139 participants who completed the study in accordance with the protocol (Per Protokol-analysis). The data analysis was based on a non-inferiority (or comparability) statistical design for efficacy endpoints.

Results: The antitussive effect of rengalin was significantly comparable (p < 0.025) with that of codelac; the time to complete resolution of cough (both daytime and nocturnal) was 7.2 ± 1.0 days (versus 7.0 ± 1.1 in the group of codelac). Rengalin's efficacy was evidenced by a sufficiently reduced cough severity in the initial few days after treatment onset. As a result of the entire 7-day treatment, the severity score was reduced by 3.1 ± 09 (versus 3.1 ± 1.0 in the group of codelac; p < 0.05), totaling 0.2 ± 0.5 point in both groups at the end of the administration period. The frequent non-productive/dry cough was fully resolved in 76% of patients. All the participants in Rengalin group achieved either convalescent outcomes or significant improvement; none of the patients developed secondary bacterial complications. Positive changes in the patients' state over the week were finally confirmed by evaluating the total quality of life scores, including physical and mental component scores (SF-36 questionnaire), and total sleep quality scores, which were comparative between patients treated with rengalin and codelac (p < 0.025). At the end of the administration period, the effect of rengalin was rated by the physician investigators as 'pronounced'. The Clinical Global Impression Scale-Efficacy Indices (CGI-EI) in the groups of rengalin and codelac were comparable, equating a score of 3.7 ± 0.5 (p < 0.025). The safety outcomes of rengalin treatment were assessed across all 143 randomized patients. The drug's high safety profile was confirmed by the absence of adverse events that could be reliably related to the study treatment, and by monitoring of laboratory variables. Rengalin demonstrated good tolerability and favorable compatibility with other medications for URIs with concomitant pathology. The patients showed 100% treatment compliance.

Conclusions: Rengalin is a new efficacious and safe drug indicated for the treatment of URI-induced cough. The severity of daytime and nocturnal cough begins to decrease as soon as on the first day after rengalin administration, with severity reduction observed throughout the whole treatment period. At the completion of the 7-day administration, cough severity is reduced by almost 100% and its changes are comparable with the outcomes of treatment with codelac. By targeting various cough reflex mediators, rengalin enables achieving an antitussive effect in the early days after URI onset (in dry, irritative cough episodes), and a protussive effect at later points of treatment. Rengalin promotes resolution of URI-induced cough without development of secondary bacterial complications.