Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury (CHARTER-Irl)

University College Hospital Galway

Status and phase: Completed; Phase 2; Phase 1

Conditions: Ventilation Perfusion Mismatch; Covid19; ARDS, Human; Lung Injury, Acute

Treatments: Drug: Nebulised heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT04511923

NUIG-2020-003

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

To be eligible, a patient must satisfy all these inclusion criteria:

1. Confirmed or suspected COVID-19. Note, if 'suspected', results must be pending or testing intended
2. Ability to obtain informed consent/assent to participate in study
3. Age 18 years or older
4. Requiring high flow nasal oxygen or positive pressure ventilator support or invasive mechanical ventilation for a time period of no greater than 48 hours
5. D-dimers > 200 ng/ml
6. PaO2 to FIO2 ratio less than or equal to 300
7. Acute opacities on chest imaging affecting at least one lung quadrant. Note 'Acute opacities' do not include effusions, lobar/lung collapse or nodules
8. 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:

1. Enrolled in another clinical trial that is unapproved for co-enrolment
2. Heparin allergy or heparin-induced thrombocytopaenia
3. APTT > 100 seconds
4. Platelet count < 50 x 109 per L
5. Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
6. Uncontrolled bleeding
7. Pregnant or suspected pregnancy (Urine or serum HCG will be recorded)
8. Receiving or about to commence ECMO or HFOV
9. Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
10. Usually receives home oxygen
11. Dependent on others for personal care due to physical or cognitive decline (pre-morbid status)
12. Death is imminent or inevitable within 24 hours
13. The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
14. Clinician objection.
15. The use or anticipated use of nebulised tobramycin during this clinical episode
16. Any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here
17. Relapse in clinical condition in patient that had fully weaned from advanced respiratory support
18. Any systemic anticoagulation other than prophylactic anticoagulation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Standard Care

No Intervention group

Description:

Standard care

Heparin

Experimental group

Description:

Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days

Treatment:

Drug: Nebulised heparin