ReviewCritical care (London, England)2020
Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.
Review in Critical care (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 63 papers.
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.
Can Nebulised HepArin Reduce morTality and Time to Extubation in Patients With COVID-19 Requiring Mechanical Ventilation Meta-Trial (CHARTER-MT): Protocol for an Investigator-initiated International Meta-trial of Randomised Studies
INHALEd Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 Meta-trial
INHALEd Unfractionated HEParin for the Treatment of Hospitalized Patients With COVID-19 Pneumonia
INHALEd Nebulised Unfractionated HEParin for the Treatment of Hospitalised Patients With COVID-19 (INHALE-HEP) Australia
A Randomised, Placebo-controlled Trial to Investigate the Efficacy of Intranasal Heparin Treatment to Reduce Transmission of SARS-CoV-2 Infection and COVID 19 Disease Among Household Contacts of SARS-CoV-2+ Adults and Children
Who cites it
63 citing papers in PubMed, 109 citations in OpenAlex.
- Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospitalised patients with COVID-19 pneumonia: a randomized controlled clinical trial.BMC pulmonary medicine · 2025Trial
- Review
- LPAR1 Promotes Activation of Pathways Alveolar Hypercoagulation and Fibrinolytic Inhibition in ARDS via NF-κB Signaling Pathway.FASEB bioAdvances · 2025Article
- Efficacy of inhaled nebulised unfractionated heparin to prevent intubation or death in hospitalised patients with COVID-19: an investigator-initiated international meta-trial of randomised clinical studies.EClinicalMedicine · 2025Article
- COVID-19 and anticoagulation: evidence from a meta-analysis of randomized controlled trials.Journal of thoracic disease · 2025Article
- Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study.Intensive care medicine experimental · 2025Article
- Physiology and pathophysiology of mucus and mucolytic use in critically ill patients.Critical care (London, England) · 2025Review
- Acute aortic dissection-induced acute respiratory distress syndrome: pathogenesis and clinical implications.Frontiers in cardiovascular medicine · 2025Review
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis.Journal of intensive care · 2024Article
- Anticoagulant therapy in COVID-19: A narrative review.Clinical and translational science · 2023Review
- Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2023Article
- Biopharmaceutical Assessment of Mesh Aerosolised Plasminogen, a Step towards ARDS Treatment.Pharmaceutics · 2023Article
- Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Nebulized Heparin to Reduce COVID-19-induced Acute Lung Injury: A Prospective Observational Study.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2023Article
- Crosstalk between Inflammation and Hemorrhage/Coagulation Disorders in Primary Blast Lung Injury.Biomolecules · 2023Review
- Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics.Carbohydrate polymers · 2023Review
- Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19.Pathology, research and practice · 2023Review
- Treatment of respiratory viral infections through inhalation therapeutics: Challenges and opportunities.Pulmonary pharmacology & therapeutics · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
Indexed as
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.