Randomized Trial Comparing Levodropropizine, Codeine, Hedera Helix, and Placebo for the Treatment of Acute Cough: A Chao Tos Study Protocol

Introduction:: Upper respiratory tract infections (URTIs) affect millions globally, with cough being one of the most bothersome symptoms. While various treatments exist, their comparative effectiveness remains unclear. This study aims to evaluate and compare three commonly used treatments for acute cough in adults with upper respiratory tract infections: Levodropropizine, Codeine (with Pseudoephedrine and chlorphenamine), and Hedera Helix extract. Methods:: We will conduct a double-blind, parallel-group randomized clinical trial with 136 adults aged 18-65 with acute upper respiratory tract infection and moderate to severe cough. Participants will be randomized to receive Levodropropizine, Codeine + Pseudoephedrine + Chlorphenamine, Hedera Helix Extract, or Placebo three times a day for 4 days. Outcomes:: The primary outcome will be cough severity at 48 hours, measured by a cough numerical rating scale. Secondary outcomes will include cough severity and duration at 4- and 10-day intervals. Discussion:: We will conduct a rigorous clinical trial addressing several methodological challenges of previous studies and conduct the first direct head-to-head comparison of three commonly used medications to treat acute cough in adults with URTIs. Conclusion:: This trial will provide high-quality evidence comparing the effectiveness of three widely used antitussive medications in primary care settings. The results would help establish evidencebased guidelines for treating acute cough in upper respiratory infections. Clinical Trial Registration Number:: ClinicalTrials.gov NCT06907355.