Covid19Phase 2/3CHARTER-MTNCT04545541
Nebulised Heparin in Patients With Severe COVID-19
A Phase 2/3 study testing Nebulised unfractionated heparin (UFH) in people with Covid19 and Respiratory Failure, run by Australian National University at 1 site in United States.
Trial summary
The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospective collaborative individual patient data analysis of randomised controlled trials and early phase studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Respiratory Failure
- What is being tested?
- Nebulised unfractionated heparin (UFH)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2020to 9 Apr 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Currently in an intensive care unit (ICU) or scheduled for transfer to the ICU. During the pandemic, critically ill inpatients might be cared for outside of the walls of the usual physical environment of ICU. For this reason, ICU is defined as an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided.
- Endotracheal tube in place
- Intubated yesterday or today
- PaO2 to FIO2 ratio less than or equal to 300 while intubated
- Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least one lung quadrant on chest X-ray or CT
- The acute opacities on chest X-ray or CT are most likely due to COVID-19
- There is a PCR positive sample for SARS-CoV-2 within the past 21 days or there are results pending or further testing is planned. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient.
Who cannot join
- Enrolled in another clinical trial that is unapproved for co-enrolment
- Heparin allergy or heparin-induced thrombocytopaenia (HIT)
- APTT > 120 seconds and this is not due to anticoagulant therapy
- Platelet count < 20 x 109 per L
- Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
- Uncontrolled bleeding
Show all 16Show fewer
- Pregnant or might be pregnant. Females aged 18-49 years are excluded unless there is documented menopause or hysterectomy or a pregnancy test was performed and is negative.
- Receiving or about to commence extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)
- Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
- Acute brain injury that may result in long-term disability
- Usually receives home oxygen
- Dependent on others for personal care due to physical or cognitive decline
- Death is imminent or inevitable within 24 hours
- The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
- Clinician objection
- Refusal of participant (person responsible) consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Frederick Health Hospital
Frederick, Maryland, 21701
About this study
Official title: 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
The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospective collaborative individual patient data analysis of randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries, including Australia, Ireland, the USA, and the UK.
Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care (open label studies) or placebo (blinded placebo controlled studies) for up to 10 days while mechanically ventilated. All trials will collect a minimum core dataset. The primary outcome for the meta-trial is ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Individual studies may have additional outcomes.
- Conditions
- Covid19, Respiratory Failure
- Being tested
- Nebulised unfractionated heparin (UFH)
- Keywords
- COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nebulised unfractionated heparin (UFH)Drug
Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Nebulised heparin | Experimental | Participants assigned to "nebulised UFH" will receive nebulised UFH in addition to the standard care required as determined by the treating team. Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days. Receives: Drug: Nebulised unfractionated heparin (UFH) |
| Control group | No intervention | Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin (Australia, Ireland). Participants assigned to "placebo" will receive Nebulised 0.9% Sodium Chloride (5 mL) administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days (USA). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alive and Ventilator Free Score
Validated hierarchical composite endpoint, based on mortality and ventilator free days, which is less prone to favour a treatment with discordant effects on survival and days free of ventilation.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2020
- Study start1 Nov 2020
- Primary completion30 Apr 2024
- Study completion9 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australian National University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frank van Haren, Australian National University
- Investigators
- Frank MP van Haren, MD, PhD, Study chair, Australian National University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04545541
- Sponsor's protocol ID
- CHARTER meta-trial
- Acronym
- CHARTER-MT
- Status last verified
- Jan 2025
- First submitted
- 5 Sep 2020
- Last updated
- 5 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The CHARTER-MT Collaborative Research Group's executive committee, with representatives from each individual country/trial, is responsible for the meta-trial's study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Investigators from individual trials have ownership of their trial data. A memorandum of understanding and data sharing agreement between investigators will facilitate and govern the pooling and meta-analysing of de-identified individual patient data from individual trials, as well as outline authorship.
Publications
van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.
PubMed 32698853
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04545541
- Acronym / sponsor ID
- CHARTER-MT / CHARTER meta-trial
- Conditions
- Covid19, Respiratory Failure
- Keywords
- COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Australian National UniversityUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 9 Apr 2025 (actual)
- First posted
- 11 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospective collaborative individual patient data analysis of randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries, including Australia, Ireland, the USA, and the UK.
Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care (open label studies) or placebo (blinded placebo controlled studies) for up to 10 days while mechanically ventilated. All trials will collect a minimum core dataset. The primary outcome for the meta-trial is ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Individual studies may have additional outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nebulised heparin | Experimental | Drug: Nebulised unfractionated heparin (UFH)Participants assigned to "nebulised UFH" will receive nebulised UFH in addition to the standard care required as determined by the treating team. Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days. |
| Control group | No intervention | –Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin (Australia, Ireland). Participants assigned to "placebo" will receive Nebulised 0.9% Sodium Chloride (5 mL) administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days (USA). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 years or older
- Currently in an intensive care unit (ICU) or scheduled for transfer to the ICU. During the pandemic, critically ill inpatients might be cared for outside of the walls of the usual physical environment of ICU. For this reason, ICU is defined as an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided.
- Endotracheal tube in place
- Intubated yesterday or today
- PaO2 to FIO2 ratio less than or equal to 300 while intubated
Key exclusion criteria (16 listed)
- Enrolled in another clinical trial that is unapproved for co-enrolment
- Heparin allergy or heparin-induced thrombocytopaenia (HIT)
- APTT > 120 seconds and this is not due to anticoagulant therapy
- Platelet count < 20 x 109 per L
- Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nebulised unfractionated heparin (UFH)Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days. | Drug | Nebulised heparin |
Primary outcome
Alive and Ventilator Free Score
Time frame: Day 28
Validated hierarchical composite endpoint, based on mortality and ventilator free days, which is less prone to favour a treatment with discordant effects on survival and days free of ventilation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2025.
- Background: PubMed 32698853van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.
- Individual participant dataSharing planned: Yes. The CHARTER-MT Collaborative Research Group's executive committee, with representatives from each individual country/trial, is responsible for the meta-trial's study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Investigators from individual trials have ownership of their trial data. A memorandum of understanding and data sharing agreement between investigators will facilitate and govern the pooling and meta-analysing of de-identified individual patient data from individual trials, as well as outline authorship.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank MP van Haren, MD, PhD study chair
Australian National University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Nebulised unfractionated heparin (UFH) in people with Covid19 and Respiratory Failure, run by Australian National University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alive and Ventilator Free Score (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04545541, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2025.