Trial reportJCI insight2025
Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.
Trial report in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Targeting SLK protects against cerebral ischemia-reperfusion injury by regulating USP8-mediated HIF-1α stabilization and RhoA/ROCK activation.Cellular & molecular biology letters · 2026Article
- Interpretable machine learning models for predicting perioperative myocardial injury in non-cardiac surgery.European heart journal. Digital health · 2026Article
- GBP5 Aggravates Acute Lung Injury Via NLRP3 Inflammasome Activation While Inducing a HIF-1α-CD73-adenosine Feedback Loop.Inflammation · 2026Article
- Hypoxia inducible factors regulate pneumovirus replication by enhancing innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Modulation of Neutrophil Recruitment and Inflammatory Signaling in Acute Respiratory Distress Syndrome by Leukotriene Inhibitors Montelukast and Zileuton.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
Hypoxia-inducible factors (HIFs) promote lung protection and pathogen eradication during acute lung injury. We, therefore, tested the theory that pharmacologic stabilization of HIFs dampens lung injury during SARS-CoV-2 pneumonia. Initial studies in murine SARS-CoV-2 models showed improved outcomes after treatment with the FDA-approved HIF stabilizer vadadustat. Subsequent studies in genetic models implicated alveolus-expressed Hif1a in mediating lung protection. Therefore, we performed a randomized, double-blinded, multicenter phase II trial in patients admitted for SARS-CoV-2 infection and concomitant hypoxia (SpO2 ≤ 94%). Patients (n = 448) were randomized to oral vadadustat (900 mg/day) or placebo for up to 14 days. Safety events were similar between the 2 groups. Vadadustat treatment induced surrogate HIF target genes. The primary outcome of severe lung injury requiring high oxygen support on day 14 occurred in 43 patients in the vadadustat group and 53 patients in the placebo group (estimated probability, 13.3% vs. 16.9%). Among patients with baseline fraction of inspired oxygen of 80% or higher (n = 106), the estimated probability of the primary outcome was 12.1% (vadadustat) versus 79.1% (placebo), indicating an even greater benefit in patients with more severe baseline hypoxia. HIF1A is a likely therapeutic target during SARS-CoV-2-associated lung injury. Robust clinical trials of HIF stabilizers during pathogen-associated lung injury are warranted.
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What Socratic 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 Socratic graph.