Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury

Covid19 Clinical Trial

— CHARTER-Irl  

Official title:

Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04511923
• Other study ID #: NUIG-2020-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 23, 2020
• Est. completion date: January 2022

Study information

• Verified date: February 2021
• Source: University College Hospital Galway
• Contact: John Laffey
• Phone: +353 91 544074
• Email: John.laffey[@]nuigalway.ie
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS, Human
• Covid19
• Lung Injury
• Lung Injury, Acute
• Respiratory Distress Syndrome, Adult
• Ventilation Perfusion Mismatch
• Wounds and Injuries

Intervention

Drug:
• Nebulised heparin
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days

Locations

Country	Name	City	State
Ireland	University Hospital Galway	Galway

Sponsors (1)

Lead Sponsor	Collaborator
University College Hospital Galway

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	D-dimer profile	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.	Up to day 10.
Primary	Frequenccy of Severe Adverse Outcomes	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.	Up to day 60
Secondary	Oxygenation Index	Determine the impact of nebulised heparin on oxygenation index	Up to day 10
Secondary	Indices of Inflammation	Effect of nebulised heparin on indices of inflammation (Interleukin (IL)-1ß, 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)	Up to day 10
Secondary	Ratios of Indices of Inflammation	Effect of nebulised heparin on the ratios of IL-1ß/IL-10 and IL-6/IL-10 will also be assessed.	Up to day 10
Secondary	Indices of Coagulation	Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).	Up to day 10
Secondary	Quasi-Static Lung Compliance	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.	Up to day 10
Secondary	Time to separation from advanced respiratory support	Time to separation from advanced respiratory support, where non survivors are treated as though not separated from advanced respiratory support.	Up to day 28
Secondary	Number treated with neuromuscular blockers	Number treated with neuromuscular blockers instituted after enrolment	Up to day 10
Secondary	Number treated with Prone positioning	Number treated with prone positioning instituted after enrolment	Up to day 10
Secondary	Number treated with extra-corporeal membrane oxygenation	Number treated with extra-corporeal membrane oxygenation instituted after enrolment	Up to day 10
Secondary	Number requiring Tracheostomy	Number tracheotomised	Up to day 28
Secondary	Time to separation from invasive ventilation among survivors	Time to separation from invasive ventilation among survivors	Up to day 28
Secondary	Discharge to ward	Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care	Up to day 28
Secondary	Discharge to ward in survivors	Time to discharge from the ICU to day 28, among survivors	Up to day 28
Secondary	Patient Survival	Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60	Up to day 60
Secondary	Number of patients residing at home or in a community setting at day 60	Number residing at home or in a community setting at day 60	Up to day 60
Secondary	Number of surviving patients residing at home or in a community	Number residing at home or in a community setting at day 60, among survivors	Up to day 60
Secondary	Ventilatory ratio	Effect of nebulised heparin on ventilatory ratio measured every 6 hours	Up to day 10
Secondary	Number treated with awake prone positioning	Number of patients treated with awake prone positioning	Up to day 10