Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context
Summary: Background: The antitussive potential of flupentixol-melitracen, an anti-anxiety and anti-depression compound, has been observed previously. We aimed to further evaluate its efficacy and safety in patients with refractory chronic cough (RCC) who were unresponsive to any other available tre...
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Elsevier
2025-08-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537025002998 |
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| author | Qiang Chen Mengru Zhang Li Zhang Alimire Aierken Ran Dong Xianghuai Xu Li Yu Kefang Lai Zhongmin Qiu |
| author_facet | Qiang Chen Mengru Zhang Li Zhang Alimire Aierken Ran Dong Xianghuai Xu Li Yu Kefang Lai Zhongmin Qiu |
| author_sort | Qiang Chen |
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| description | Summary: Background: The antitussive potential of flupentixol-melitracen, an anti-anxiety and anti-depression compound, has been observed previously. We aimed to further evaluate its efficacy and safety in patients with refractory chronic cough (RCC) who were unresponsive to any other available treatments. Methods: This randomised, double-blinded, placebo-controlled clinical trial was conducted at a single specialist cough clinic in Tongji Hspital, Shanghai, China. Adults aged 18–69 years with RCC and persistent cough despite at least two weeks of neuromodulator therapy were enrolled. Participants were randomly assigned (1:1) to receive either oral flupentixol-melitracen (flupentixol 0.5 mg + melitracen 10 mg), one tablet twice daily, or matching placebo, for two weeks, followed by a one week of off-treatment safety monitoring. Randomisation was computer-generated, with masking of participants, investigators, and outcome assessors. The co-primary endpoints were cough resolution rate (≥50% reduction in cough symptom score [CSS]) at visit four and placebo-adjusted change in CSS over time. The full analysis set (FAS) was used following the modified intention-to-treat (mITT) principle for demographic baseline analysis and efficacy analysis. The safety set (SS) was used for safety analysis and included all patients who took at least one dose of treatment and had post-dose safety records. The FAS and SS were equivalent in this study. The trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000035304. Findings: Between March 9th, 2021 and December 1st, 2023, 102 patients were enrolled and randomised. A total of 99 patients received at least one dose of treatment and were included in the primary and safety analyses (49 taking flupentixol-melitracen and 50 taking placebo). At visit four, flupentixol-melitracen arm reached significantly higher cough resolution rate (65.3% [32/49] vs 32.0% [16/50]; p = 0.0009). The adjusted mean reduction in CSS was 0.144 points greater in the flupentixol-melitracen group than in the placebo group over time (p = 0.0034). Treatment-emergent adverse events occurred in 51.0% (15/49) of patients in the flupentixol-melitracen group and 34.0% (17/50) in the placebo group. No serious adverse events or treatment-related deaths were reported. All adverse events were mild and resolved after discontinuation. Interpretation: Our findings suggest that short-term use of flupentixol-melitracen may be an effective and well-tolerated treatment for RCC. However, the findings should be interpreted with caution due to key limitations, including the absence of objective cough frequency measurement and limited generalisability beyond a single-centre population. These factors may influence the precision and applicability of the observed treatment effect. Further trials using objective endpoints and longer follow-up in broader populations are needed to confirm efficacy and safety. Funding: The Project of Science and Technology Commission of Shanghai Municipality. |
| format | Article |
| id | doaj-art-3bc3ce8ff2b642bb87e857eefc0ebf40 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-3bc3ce8ff2b642bb87e857eefc0ebf402025-08-20T03:39:05ZengElsevierEClinicalMedicine2589-53702025-08-018610336710.1016/j.eclinm.2025.103367Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in contextQiang Chen0Mengru Zhang1Li Zhang2Alimire Aierken3Ran Dong4Xianghuai Xu5Li Yu6Kefang Lai7Zhongmin Qiu8Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; Centre for Clinical Science, Respiratory Medicine, Hull York Medical School, University of Hull, Castle Hill Hospital, Castle Road, Cottingham, UKDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Corresponding author.Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; Corresponding author. Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.Summary: Background: The antitussive potential of flupentixol-melitracen, an anti-anxiety and anti-depression compound, has been observed previously. We aimed to further evaluate its efficacy and safety in patients with refractory chronic cough (RCC) who were unresponsive to any other available treatments. Methods: This randomised, double-blinded, placebo-controlled clinical trial was conducted at a single specialist cough clinic in Tongji Hspital, Shanghai, China. Adults aged 18–69 years with RCC and persistent cough despite at least two weeks of neuromodulator therapy were enrolled. Participants were randomly assigned (1:1) to receive either oral flupentixol-melitracen (flupentixol 0.5 mg + melitracen 10 mg), one tablet twice daily, or matching placebo, for two weeks, followed by a one week of off-treatment safety monitoring. Randomisation was computer-generated, with masking of participants, investigators, and outcome assessors. The co-primary endpoints were cough resolution rate (≥50% reduction in cough symptom score [CSS]) at visit four and placebo-adjusted change in CSS over time. The full analysis set (FAS) was used following the modified intention-to-treat (mITT) principle for demographic baseline analysis and efficacy analysis. The safety set (SS) was used for safety analysis and included all patients who took at least one dose of treatment and had post-dose safety records. The FAS and SS were equivalent in this study. The trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000035304. Findings: Between March 9th, 2021 and December 1st, 2023, 102 patients were enrolled and randomised. A total of 99 patients received at least one dose of treatment and were included in the primary and safety analyses (49 taking flupentixol-melitracen and 50 taking placebo). At visit four, flupentixol-melitracen arm reached significantly higher cough resolution rate (65.3% [32/49] vs 32.0% [16/50]; p = 0.0009). The adjusted mean reduction in CSS was 0.144 points greater in the flupentixol-melitracen group than in the placebo group over time (p = 0.0034). Treatment-emergent adverse events occurred in 51.0% (15/49) of patients in the flupentixol-melitracen group and 34.0% (17/50) in the placebo group. No serious adverse events or treatment-related deaths were reported. All adverse events were mild and resolved after discontinuation. Interpretation: Our findings suggest that short-term use of flupentixol-melitracen may be an effective and well-tolerated treatment for RCC. However, the findings should be interpreted with caution due to key limitations, including the absence of objective cough frequency measurement and limited generalisability beyond a single-centre population. These factors may influence the precision and applicability of the observed treatment effect. Further trials using objective endpoints and longer follow-up in broader populations are needed to confirm efficacy and safety. Funding: The Project of Science and Technology Commission of Shanghai Municipality.http://www.sciencedirect.com/science/article/pii/S2589537025002998AnxietyDepressionFlupentixol-melitracenPlaceboRefractory chronic cough |
| spellingShingle | Qiang Chen Mengru Zhang Li Zhang Alimire Aierken Ran Dong Xianghuai Xu Li Yu Kefang Lai Zhongmin Qiu Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context EClinicalMedicine Anxiety Depression Flupentixol-melitracen Placebo Refractory chronic cough |
| title | Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context |
| title_full | Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context |
| title_fullStr | Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context |
| title_full_unstemmed | Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context |
| title_short | Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trialResearch in context |
| title_sort | efficacy and safety of flupentixol melitracen in patients with refractory chronic cough a randomised double blinded placebo controlled clinical trialresearch in context |
| topic | Anxiety Depression Flupentixol-melitracen Placebo Refractory chronic cough |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025002998 |
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