CHARTER-Irl: Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury
Study Details
Study Description
Brief Summary
The investigators present a randomised open label phase Ib/IIa trial of nebulised unfractionated heparin to evaluate the effect of nebulised unfractionated heparin on the procoagulant response in ICU patients with SARS-CoV-2 requiring advanced respiratory support. As this is one of the first studies of nebulised heparin in COVID 19 lung disease the investigators will assess safety as a co-primary outcome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Standard Care Standard care |
|
| Experimental: Heparin Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days |
Drug: Nebulised heparin
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days
|
Outcome Measures
Primary Outcome Measures
- D-dimer profile [Up to day 10.]
Effect of nebulised heparin on d-dimer profile, assessed via d-dimer AUC and via a mixed effects model, with data collected on days 1, 3, 5 and 10.
- Frequenccy of Severe Adverse Outcomes [Up to day 60]
Safety of nebulised heparin delivered by aerogen solo nebuliser in patients with COVID-19 induced severe respiratory failure, as measured by the incidence of severe adverse events.
Secondary Outcome Measures
- Oxygenation Index [Up to day 10]
Determine the impact of nebulised heparin on oxygenation index
- Indices of Inflammation [Up to day 10]
Effect of nebulised heparin on indices of inflammation (Interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1), C-reactive protein, procalcitonin, Ferritin,) will be assessed (AUC on days 1, 3, 5 and 10)
- Ratios of Indices of Inflammation [Up to day 10]
Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.
- Indices of Coagulation [Up to day 10]
Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).
- Quasi-Static Lung Compliance [Up to day 10]
Determine the effect of nebulised heparin on Quasi-Static Lung Compliance (i.e. tidal volume/(Plateau pressure-PEEP) measured on days 1,3,5,10.
- Time to separation from advanced respiratory support [Up to day 28]
Time to separation from advanced respiratory support, where non survivors are treated as though not separated from advanced respiratory support.
- Number treated with neuromuscular blockers [Up to day 10]
Number treated with neuromuscular blockers instituted after enrolment
- Number treated with Prone positioning [Up to day 10]
Number treated with prone positioning instituted after enrolment
- Number treated with extra-corporeal membrane oxygenation [Up to day 10]
Number treated with extra-corporeal membrane oxygenation instituted after enrolment
- Number requiring Tracheostomy [Up to day 28]
Number tracheotomised
- Time to separation from invasive ventilation among survivors [Up to day 28]
Time to separation from invasive ventilation among survivors
- Discharge to ward [Up to day 28]
Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care
- Discharge to ward in survivors [Up to day 28]
Time to discharge from the ICU to day 28, among survivors
- Patient Survival [Up to day 60]
Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60
- Number of patients residing at home or in a community setting at day 60 [Up to day 60]
Number residing at home or in a community setting at day 60
- Number of surviving patients residing at home or in a community [Up to day 60]
Number residing at home or in a community setting at day 60, among survivors
- Ventilatory ratio [Up to day 10]
Effect of nebulised heparin on ventilatory ratio measured every 6 hours
- Number treated with awake prone positioning [Up to day 10]
Number of patients treated with awake prone positioning
Eligibility Criteria
Criteria
Inclusion Criteria:
To be eligible, a patient must satisfy all these inclusion criteria:
-
Confirmed or suspected COVID-19. Note, if 'suspected', results must be pending or testing intended
-
Ability to obtain informed consent/assent to participate in study
-
Age 18 years or older
-
Requiring high flow nasal oxygen or positive pressure ventilator support or invasive mechanical ventilation for a time period of no greater than 48 hours
-
D-dimers > 200 ng/ml
-
PaO2 to FIO2 ratio less than or equal to 300
-
Acute opacities on chest imaging affecting at least one lung quadrant. Note 'Acute opacities' do not include effusions, lobar/lung collapse or nodules
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Currently in a higher level of care area designated for inpatient care of patients where therapies including non-positive pressure ventilatory support can be provided.
Exclusion criteria
To be eligible, a patient must have none of these exclusion criteria:
-
Enrolled in another clinical trial that is unapproved for co-enrolment
-
Heparin allergy or heparin-induced thrombocytopaenia
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APTT > 100 seconds
-
Platelet count < 50 x 109 per L
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Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
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Uncontrolled bleeding
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Pregnant or suspected pregnancy (Urine or serum HCG will be recorded)
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Receiving or about to commence ECMO or HFOV
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Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
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Usually receives home oxygen
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Dependent on others for personal care due to physical or cognitive decline (pre-morbid status)
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Death is imminent or inevitable within 24 hours
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The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
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Clinician objection.
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The use or anticipated use of nebulised tobramycin during this clinical episode
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Any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here
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Relapse in clinical condition in patient that had fully weaned from advanced respiratory support
-
Any systemic anticoagulation other than prophylactic anticoagulation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Galway | Galway | Ireland |
Sponsors and Collaborators
- University College Hospital Galway
Investigators
- Principal Investigator: John Laffey, Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NUIG-2020-003