Nebulized Heparin for Severe COVID-19

(CHARTER-MT Trial)

Overseen By Frank MP van Haren, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Australian National University

Disqualifiers: Heparin allergy, Pregnancy, ECMO, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 days

57 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug nebulised unfractionated heparin (UFH) for severe COVID-19?

Research suggests that nebulised UFH may help reduce lung damage and improve outcomes in COVID-19 patients by preventing blood clots in the lungs and reducing inflammation. In a study, patients receiving nebulised UFH showed lower mortality rates and improved clinical scores compared to those receiving standard care, especially when they received at least six doses of the drug. ^{1 2 3 4 5}

Is nebulized heparin safe for use in humans?

Nebulized unfractionated heparin (UFH) has been tested in patients with COVID-19 and was found to be well tolerated without causing significant adverse events. It has also been safely used in other inflammatory respiratory diseases, suggesting it is generally safe for human use. ^{1 2 3 4 5}

How does nebulized unfractionated heparin differ from other COVID-19 treatments?

Nebulized unfractionated heparin is unique because it is inhaled directly into the lungs, where it can help prevent blood clots and reduce inflammation, which are common issues in severe COVID-19 cases. It also has antiviral properties that may help inactivate the virus and prevent it from entering cells, making it different from other treatments that are typically administered systemically (throughout the body). ^{1 2 3 4 5}

Research Team

Frank MP van Haren, MD, PhD

Principal Investigator

Australian National University

Eligibility Criteria

This trial is for adults over 18 who are intubated in the ICU with severe COVID-19, showing lung opacities likely due to the virus. They must have been intubated recently and not be pregnant, allergic to heparin, or have certain bleeding disorders or other conditions that could interfere with treatment.

Inclusion Criteria

I am currently in the ICU or will be moved there soon.

You have a breathing tube in your throat.

I am 18 years old or older.

Exclusion Criteria

I have a brain injury that could cause long-term disability.

I am currently on or about to start ECMO or HFOV treatment.

My clinical team cannot set up the required nebulizer and ventilator with humidification for the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive nebulised heparin or standard care/placebo while mechanically ventilated

Up to 10 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for ventilator-free days and survival

28 days

Treatment Details

Interventions

• Nebulised unfractionated heparin (UFH)

Trial Overview The CHARTER-MT study tests if nebulised unfractionated heparin can help patients on mechanical ventilation recover faster from severe COVID-19. Patients will receive either heparin or standard care/placebo every six hours for up to ten days while ventilated.

Participant Groups

Group I: Nebulised heparin Experimental Treatment 1 Intervention

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.

Group II: Control group Active Control 1 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 Is Running the Clinical Trial?

Australian National University

Lead Sponsor

Trials

19

Recruited

10,000+

References

1. England pubmed.ncbi.nlm.nih.gov

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Can nebulised HepArin Reduce morTality and time to Extubation in patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT): Protocol and statistical analysis plan for an investigator-initiated international meta-trial of prospective randomised clinical studies. [2022]