Clinical trial NCT04511923: Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury
Official title: Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
ARDS, Human
Lung Injury, Acute
Ventilation Perfusion Mismatch
Lead sponsor: University College Hospital Galway
Sponsor class: OTHER
First posted: 2020-08-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: D-dimer profile
timeFrame: Up to day 10.
measure: Frequenccy of Severe Adverse Outcomes
timeFrame: Up to day 60
Secondary outcomes:
measure: Oxygenation Index
timeFrame: Up to day 10
measure: Indices of Inflammation
timeFrame: Up to day 10
measure: Ratios of Indices of Inflammation
timeFrame: Up to day 10
measure: Indices of Coagulation
timeFrame: Up to day 10
measure: Quasi-Static Lung Compliance
timeFrame: Up to day 10
measure: Time to separation from advanced respiratory support
timeFrame: Up to day 28
measure: Number treated with neuromuscular blockers
timeFrame: Up to day 10
measure: Number treated with Prone positioning
timeFrame: Up to day 10
measure: Number treated with extra-corporeal membrane oxygenation
timeFrame: Up to day 10
measure: Number requiring Tracheostomy
timeFrame: Up to day 28
measure: Time to separation from invasive ventilation among survivors
timeFrame: Up to day 28
measure: Discharge to ward
timeFrame: Up to day 28
measure: Discharge to ward in survivors
timeFrame: Up to day 28
measure: Patient Survival
timeFrame: Up to day 60
measure: Number of patients residing at home or in a community setting at day 60
timeFrame: Up to day 60
measure: Number of surviving patients residing at home or in a community
timeFrame: Up to day 60
measure: Ventilatory ratio
timeFrame: Up to day 10
measure: Number treated with awake prone positioning
timeFrame: Up to day 10
Other outcomes:
Locations:
city: Galway
country: Ireland
facility: University Hospital Galway
Study officials:
affiliation: Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland
name: John Laffey
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sheehan JR, Calpin P, Kernan M, Kelly C, Casey S, Murphy D, Alvarez-Iglesias A, Giacomini C, Cody C, Curley G, McGeary S, Hanley C, McNicholas B, van Haren F, Laffey JG, Cosgrave D. The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial. Trials. 2022 Sep 14;23(1):774. doi: 10.1186/s13063-022-06518-z.