Efficacy and Safety of Suhuang Zhike Capsule for Post-infectious Cough: A Multicenter, Single-arm, Open-label Phase IV Study.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang Zhike Capsule is an approved traditional Chinese medicine by the State Drug Administration for the treatment of Cough Variant Asthma (CVA) and post-infectious cough (PIC). It has been used clinically for 18 years since receiving market approval. AIM OF THE STUDY: This Phase IV clinical trial aimed to evaluate the safety and efficacy of Suhuang Zhike Capsule in treating PIC, characterize its efficacy profile in routine clinical practice, and assess adverse reactions to support its rational clinical use. MATERIALS AND METHODS: This multicenter, prospective, open-label, single-arm study enrolled adult participants meeting the diagnostic criteria for PIC and the Traditional Chinese Medicine (TCM) syndrome criteria of "wind evil invading the lung and lung qi failing to disperse syndrome". Participants received Suhuang Zhike Capsule orally (three capsules three times daily) for 14 days. The primary outcome was the change in full-day cough symptom score (CSS) between baseline and Day 14. Cough severity was assessed twice daily. Secondary outcomes included the cough resolution rate, cough relief rate, as well as the time to cough relief and cough resolution. TCM symptoms related to PIC were also evaluated using a system score. A subgroup analysis compared the efficacy of Suhuang Zhike Capsule used as a monotherapy with its combination with other respiratory medications. A generalized linear regression analysis was performed, adjusting for age, sex, and other covariates to account for potential baseline confounders. In addition, a sensitivity analysis was performed using the per-protocol set (PPS). Safety was assessed by evaluating adverse events (AEs) and laboratory test results. RESULTS: A total of 542 patients were enrolled and administered the study medication, with a follow-up loss rate of 3.14%. Suhuang Zhike Capsule significantly reduced the full-day CSS and improved other clinical symptoms in patients with PIC. Both the cough resolution rate and the cough relief rate increased with treatment duration. The change in full-day CSS between baseline and Day 14 was -2.72 ± 1.46 points, and the cough resolution rate was 86.48%. Generalized linear regression analysis indicated that concomitant use of other respiratory medications was not significantly associated with a greater reduction in full-day CSS (β = 0.394, 95% CI: -0.014 to 0.802, P = 0.059). However, a longer pre-treatment duration of cough was significantly associated with a reduced therapeutic response (β = 3.066 per week, P = 0.048). Sensitivity analyses confirmed the robustness of the primary efficacy outcome. The median time to cough relief was 3 days, and the median time to cough resolution was 8 days. Suhuang Zhike Capsule also reduced TCM symptom scores for cough frequency, cough severity, throat itching, sputum production, and shortness of breath among patients with PIC. Regarding safety, no serious adverse events (SAEs) occurred. A total of 18 patients experienced 20 treatment-related AEs, corresponding to an incidence rate of 3.32%. CONCLUSIONS: In this real-world phase IV study, Suhuang Zhike Capsule demonstrated potential efficacy and a favorable safety profile in the treatment of PIC. These results provide supportive evidence for its clinical use, while acknowledging the limitations inherent to the single-arm study design.