A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough

Sagara, Hironori; Kikuchi, Masashi; Arano, Ichiro; Sato, Asako; Shirakawa, Masayoshi; Rosa, Carmen La; Muccino, David

doi:10.1016/j.alit.2022.05.006

Cited by 7 publications

(8 citation statements)

References 33 publications

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“…After removing duplicates (n=104) and reports deemed unsuitable after screening their titles and abstracts (n=84), 27 articles were considered eligible. After full-text reading, 22 studies were further excluded due to various reasons (gefapixant not used, n=1; patients with acute cough, n=1 [ 26 ]; conference abstract, n=18; no placebo group, n=1 [ 27 ]; patients with idiopathic pulmonary fibrosis, n=1 [ 17 ]). Finally, five studies focusing on seven trials published between 2015 and 2022 were included in the current meta-analysis [ 15 , 16 , 18 , 19 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials

Chuang

Chen

et al. 2023

Eur Respir Rev

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BackgroundThe efficacy and safety of gefapixant in adults with chronic cough remain unclear. Our objective was to assess the efficacy and safety of gefapixant using updated evidence.MethodsMEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched from inception through September 2022. Subgroup analysis based on dose of gefapixant (i.e.≤20, 45–50 and ≥100 mg twice daily for low, moderate and high doses, respectively) was performed to explore a potential dose-dependent effect.ResultsFive studies involving seven trials showed the efficacy of moderate- or high-dose gefapixant for reducing objective 24-h cough frequency (estimated relative reduction 30.9% and 58.5%, respectively) (i.e.primary outcome) and awake cough frequency (estimated relative reduction 47.3% and 62.8%, respectively). Night-time cough frequency was only reduced with high-dose gefapixant. Consistently, the use of moderate- or high-dose gefapixant significantly alleviated cough severity and improved cough-related quality of life, but increased the risk of all-cause adverse events (AEs), treatment-related AEs and ageusia/dysgeusia/hypogeusia. Subgroup analysis showed dose dependency in both efficacy and AEs with a cut-off dose being ≥45 mg twice daily.ConclusionsThis meta-analysis revealed dose-dependent efficacy and adverse effects of gefapixant against chronic cough. Further studies are required to investigate the feasibility of moderate-dose (i.e.45–50 mg twice daily) gefapixant in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials

Chuang

Chen

et al. 2023

Eur Respir Rev

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“…After screening 713 titles and abstracts and 100 full-text articles, we identified 11 RCTs; of these, 2 were unpublished and only reported results on the clinical trial registration (Figure 1). For the primary analysis, we included 9 published RCTs including 2980 patients; of these 9 trials, 4 had a crossover design and 5 had a parallel design . All trials, apart from 1 that addressed alternative doses of gefapixant, compared 1 or more doses with a placebo.…”

Section: Resultsmentioning

confidence: 99%

“…For the primary analysis, we included 9 published RCTs including 2980 patients; of these 9 trials, 4 had a crossover design and 5 had a parallel design . All trials, apart from 1 that addressed alternative doses of gefapixant, compared 1 or more doses with a placebo. Industry funded all trials.…”

Section: Resultsmentioning

confidence: 99%

“…Eight RCTs including 2651 patients reported cough-specific quality of life. 12, 19,[40][41][42][43] The dose-response model suggested that, compared with placebo, use of gefapixant (45 mg twice daily) resulted in a mean increase of 1 point (95% CI, 0.7-1.4) on the LCQ measuring cough-specific quality of life (risk difference for achieving at least the MID, 9.2% [95% CI, 5.6%-12.8%]; moderate certainty) (Figure 3 and Figure 4B; eTable 4 in Supplement 1).…”

Section: Cough-specific Quality Of Lifementioning

confidence: 99%

“…Nine RCTs including 2974 patients reported taste-related adverse events. 12, 19,[39][40][41][42][43] The dose-response model suggested that, compared with placebo, gefapixant (45 mg twice daily) caused a significant increase in taste-related adverse events (RR, 9.0 [95% CI, 6.5-12.6]; high certainty), whereas at 15 mg twice daily, gefapixant caused a smaller increase (RR, 2.5 [95% CI, 2.2-2.9]; high certainty) (Figure 3 and Figure 4C). To explore the impact of including 2 unpublished RCTs, 44,45 we included these trials in a sensitivity analysis, which found similar results (eTable 5 in Supplement 1).…”

Section: Taste-related Adverse Eventsmentioning

confidence: 99%

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Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Kum,

Patel,

Diab

et al. 2023

JAMA

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ImportanceGefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.ObjectiveTo evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.Data SourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.Study SelectionTwo reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.Data Extraction and SynthesisTwo reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).Main Outcomes and MeasuresCough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.ResultsNine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, −6.2 mm [95% CI, −4.1 to −8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).Conclusions and RelevanceCompared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.

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Laryngeal Vibrotactile Stimulation Is Feasible, Acceptable To People With Unexplained Chronic Cough

Misono,

Shen,

Sombrio

et al. 2024

The Laryngoscope

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ObjectivesUnexplained chronic cough (UCC) is common and has significant impacts on quality of life. Ongoing cough can sensitize the larynx, increasing the urge to cough and perpetuating the cycle of chronic cough. Vibrotactile stimulation (VTS) of the larynx is a noninvasive stimulation technique that can modulate laryngeal somatosensory and motor activity. Study objectives were to assess feasibility and acceptability of VTS use by people with UCC. Secondarily, changes in cough‐related quality of life measures were assessed.MethodsAdults with UCC recorded cough measures at baseline and after completing 2 weeks of daily VTS. Feasibility and acceptability were assessed through participant‐reported device use and structured feedback. Cough‐related quality of life measures were the Leicester Cough Questionnaire (LCQ) and the Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ).ResultsNineteen adults participated, with mean age 67 years and cough duration 130 months. Notably, 93% of planned VTS sessions were logged, 94% of participants found the device comfortable to wear, 89% found it easy to operate and 79% would recommend it to others. Pre‐post LCQ change achieved a minimal important difference (MID) (mean 1.3 [SD 2.4, p = 0.015]). NLHQ scores improved, but did not reach an MID.ConclusionsLaryngeal VTS use was feasible and acceptable for use by patients with UCC and was associated with a meaningful improvement in cough‐related quality of life. Future studies will include VTS dose refinement and the inclusion of a comparison arm to further assess the potential for laryngeal VTS as a novel treatment modality for UCC.Level of Evidence4 Laryngoscope, 2024

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A phase 3, randomized, double-blind, clinical study to evaluate the long-term safety and efficacy of gefapixant in Japanese adult participants with refractory or unexplained chronic cough

Cited by 7 publications

References 33 publications

Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials

Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials

Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Laryngeal Vibrotactile Stimulation Is Feasible, Acceptable To People With Unexplained Chronic Cough

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