Trial reporteLife2024
Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial.
Trial report in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04359654 (A Single-site, Randomised, Controlled, Parallel Design, Open-label Investigation of an Approved Nebulised Recombinant Human DNase Enzyme), which is not on this 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.
A Single-site, Randomised, Controlled, Parallel Design, Open-label Investigation of an Approved Nebulised Recombinant Human DNase Enzyme (Dornase Alfa) to Reduce Hyperinflammation in Hospitalised Participants With COVID-19
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Investigating the Role of Neutrophil Extracellular Traps as a Therapeutic Target in Traumatic Brain Injury: a Systematic Review and Meta-analysis.Molecular neurobiology · 2025Pooled it
- Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS.Scientific reports · 2025Trial
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Neutrophil extracellular traps offer a new therapeutic target for elephant endotheliotropic herpes virus-hemorrhagic disease (EEHV-HD).Communications biology · 2026Article
- Intersecting Roles of Estrogens and Neutrophils in Modulating Innate Immunity in Cancer.Biomolecules · 2026Review
- Targeting neutrophil extracellular traps (NETs): a promising immunotherapeutic approach for pulmonary diseases.Molecular biology reports · 2026Review
- Review
- The Neutrophil-NET Axis in Immune Checkpoint Inhibitor Resistance in Non-Small Cell Lung Cancer: Roles, Biomarkers and Therapeutic Opportunities.Biomolecules · 2026Review
- The role of NETosis in breast cancer: mechanistic insights and biomarker potential.Breast cancer research : BCR · 2025Review
- Single-cell sequencing analysis and multiple machine learning methods identified immune-associated SERPINB1 and CPEB4 as novel biomarkers for COVID-19-induced ARDS.Die Naturwissenschaften · 2025Article
- A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease.International journal of molecular sciences · 2025Review
- Kinetics of DNases after hematopoietic stem cell transplant.Blood vessels, thrombosis & hemostasis · 2025Article
- A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs.Cells · 2025Article
- The Efficacy of Dornase Alpha (Polmozyme) in Resolving Persistent Atelectasis in Pediatric Critical Care.Cureus · 2025Article
- Unveiling the inflammatory messengers after intracerebral hemorrhage: the crosstalk between peripheral NETs and microglia.Frontiers in immunology · 2025Review
- Reflections on Targeting Neutrophil Extracellular Traps in Deep Vein Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Neutrophils: a key component in ECMO-related acute organ injury.Frontiers in immunology · 2024Review
- Occurrence of COVID-19 in cystic fibrosis patients: a review.Frontiers in microbiology · 2024Review
- Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia.Immunity · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
Abstract
Background: Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Methods: Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. Results: We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01-2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, p=0.004). Conclusions: Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. Funding: LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). Clinical trial number: NCT04359654.
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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.