ArticleERJ open research2021
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough.
Article in ERJ open research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- "Nebulized lidocaine for intractable cough in hospice care: a comprehensive review of efficacy, safety, and future perspectives".BMC palliative care · 2025Pooled it
- Transient receptor potential vanilloid channels in inflammatory bowel diseases: linking inflammation, angiogenesis, and oxidative stress.Inflammopharmacology · 2026Review
- Neuro-pulmonary mechanistic interplay underlying chronic cough.Breathe (Sheffield, England) · 2026Review
- Disease finds its identity with treatment in the real world: the use of gefapixant in chronic cough.ERJ open research · 2025Article
- Activation of Adenosine Triphosphate-Gated Purinergic 2 Receptor Channels by Transient Receptor Potential Vanilloid Subtype 4 in Cough Hypersensitivity.Biomolecules · 2025Article
- Combined clinical, structural and cellular studies discriminate pathogenic and benign TRPV4 variants.Brain : a journal of neurology · 2025Article
- Decoding the impact of the placebo response in clinical trials for chronic cough.ERJ open research · 2024Article
- Gain-of-function mutations of TRPV4 acting in endothelial cells drive blood-CNS barrier breakdown and motor neuron degeneration in mice.Science translational medicine · 2024Article
- Effect of TRPV4 Antagonist GSK2798745 on Chlorine Gas-Induced Acute Lung Injury in a Swine Model.International journal of molecular sciences · 2024Article
- The Therapeutic Landscape in Chronic Cough.Lung · 2024Review
- Review
- Review
- Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis.EClinicalMedicine · 2023Article
- TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.Nature communications · 2023Article
- Modulation of macrophages by biophysical cues in health and beyond.Discovery immunology · 2023Review
- Chronic cough-the limitation and advances in assessment techniques.Journal of thoracic disease · 2022Review
- TRP channels: a journey towards a molecular understanding of pain.Nature reviews. Neuroscience · 2022Review
- Objective cough frequency monitoring in real-world practice.ERJ open research · 2021Article
- Stretching the Function of Innate Immune Cells.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAirway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough.
methodsA two-period randomised, double blinded, placebo-controlled crossover study was designed with interim analyses for futility and sample size adjustment. Refractory chronic cough patients received either GSK2798745 or placebo once daily for 7 days with a washout between treatments. Pharmacokinetic samples were collected for analysis of GSK2798745 at end of study. The primary end-point was total cough counts assessed objectively during day-time hours (10 h) following 7 days of dosing.
resultsInterim analysis was performed after 12 participants completed both treatment periods. This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. At this point 17 participants had been enrolled (mean 61 years; 88% female), and 15 had completed the study. Final study results for posterior median cough counts showed a 34% (90% credible interval: -3%, +85%) numerical increase for GSK2798745 compared to placebo.
conclusionThere was no evidence of an anti-tussive effect of GSK2798745. The study design allowed the decision on lack of efficacy to be made with minimal participant exposure to the investigational drug.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.