Trial reportInternational journal of chronic obstructive pulmonary disease2018
The development of AZD7624 for prevention of exacerbations in COPD: a randomized controlled trial.
Trial report in International journal of chronic obstructive pulmonary disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell communication and signaling : CCS · 2023Pooled it
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Epithelial cells in chronic obstructive pulmonary disease exacerbations: Targets for lung repair.Pharmacological reviews · 2026Review
- Mitogen-activated protein kinase-guided drug discovery for post-viral and related types of lung disease.European respiratory review : an official journal of the European Respiratory Society · 2024Article
- Transcriptomic characterization of the human segmental endotoxin challenge model.Scientific reports · 2024Article
- CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder.Frontiers in pharmacology · 2024Article
- Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations.BMC pulmonary medicine · 2023Article
- Novel Anti-Inflammatory Approaches to COPD.International journal of chronic obstructive pulmonary disease · 2023Review
- The future of inhalation therapy in chronic obstructive pulmonary disease.Current research in pharmacology and drug discovery · 2022Review
- Safety and efficacy of p38 mitogen-activated protein kinase inhibitors (MAPKIs) in COPD.Frontiers in pharmacology · 2022Article
- Marine-Derived Compounds for the Potential Treatment of Glucocorticoid Resistance in Severe Asthma.Marine drugs · 2021Review
- Complexity of design in early phase respiratory clinical trials; evaluating impact of primary endpoints and sponsor size.Contemporary clinical trials communications · 2021Article
- Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19.Pharmacology & therapeutics · 2021Review
- Identification and treatment of T2-low asthma in the era of biologics.ERJ open research · 2021Review
- Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects.Pharmaceutics · 2021Review
- Leukocyte Function in COPD: Clinical Relevance and Potential for Drug Therapy.International journal of chronic obstructive pulmonary disease · 2021Review
- Why new biology must be uncovered to advance therapeutic strategies for chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2021Review
- Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway.PloS one · 2021Article
- Role of p38 Mitogen-Activated Protein Kinase in Asthma and COPD: Pathogenic Aspects and Potential Targeted Therapies.Drug design, development and therapy · 2021Review
- Of Mice and Monkeys: Neuroprotective Efficacy of the p38 Inhibitor BIRB 796 Depends on Model Duration in Experimental Glaucoma.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations. Objectives: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD. The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations. Methods: The p38 isoform most relevant to lung inflammation was assessed using an in situ proximity ligation assay in severe COPD patients and donor controls. Volunteers aged 18-55 years were randomized into the lipopolysaccharide (LPS) challenge study, which investigated the effect of a single dose of AZD7624 vs placebo on inflammatory biomarkers. The Proof of Principle study randomized patients aged 40-85 years with a diagnosis of COPD for >1 year to AZD7624 or placebo to assess the effect of p38 inhibition in decreasing the rate of exacerbations. Results: The p38 isoform most relevant to lung inflammation was p38α, and AZD7624 specifically inhibited p38α and p38β isoforms in human alveolar macrophages. Thirty volunteers were randomized in the LPS challenge study. AZD7624 reduced the increase from baseline in sputum neutrophils and TNF-α by 56.6% and 85.4%, respectively ( Conclusion: Although p38α is upregulated in the lungs of COPD patients, AZD7624, an isoform-specific inhaled p38 MAPK inhibitor, failed to show any benefit in patients with COPD.
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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.