Back to resultsNebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury (CHARTER-Irl)
Primary Purpose
Covid19, ARDS, Human, Lung Injury, Acute
Status
Unknown status
Phase
Phase 1
Locations
Ireland
Study Type
Interventional
Intervention
Nebulised heparin
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility 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
- 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
- APTT > 100 seconds
- Platelet count < 50 x 109 per L
- Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
- Uncontrolled bleeding
- Pregnant or suspected pregnancy (Urine or serum HCG will be recorded)
- Receiving or about to commence ECMO or HFOV
- Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
- Usually receives home oxygen
- Dependent on others for personal care due to physical or cognitive decline (pre-morbid status)
- Death is imminent or inevitable within 24 hours
- The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
- Clinician objection.
- The use or anticipated use of nebulised tobramycin during this clinical episode
- Any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here
- Relapse in clinical condition in patient that had fully weaned from advanced respiratory support
- Any systemic anticoagulation other than prophylactic anticoagulation
Sites / Locations
- University Hospital GalwayRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Standard Care
Heparin
Arm Description
Standard care
Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Oxygenation Index
Determine the impact of nebulised heparin on oxygenation index
Indices of Inflammation
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
Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.
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).
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.
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.
Number treated with neuromuscular blockers
Number treated with neuromuscular blockers instituted after enrolment
Number treated with Prone positioning
Number treated with prone positioning instituted after enrolment
Number treated with extra-corporeal membrane oxygenation
Number treated with extra-corporeal membrane oxygenation instituted after enrolment
Number requiring Tracheostomy
Number tracheotomised
Time to separation from invasive ventilation among survivors
Time to separation from invasive ventilation among survivors
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
Discharge to ward in survivors
Time to discharge from the ICU to day 28, among survivors
Patient Survival
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
Number residing at home or in a community setting at day 60
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
Ventilatory ratio
Effect of nebulised heparin on ventilatory ratio measured every 6 hours
Number treated with awake prone positioning
Number of patients treated with awake prone positioning
Full Information
NCT ID
NCT04511923
First Posted
August 10, 2020
Last Updated
February 5, 2021
Sponsor
University College Hospital Galway
1. Study Identification
Unique Protocol Identification Number
NCT04511923
Brief Title
Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury
Acronym
CHARTER-Irl
Official Title
Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 23, 2020 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
January 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University College Hospital Galway
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, ARDS, Human, Lung Injury, Acute, Ventilation Perfusion Mismatch
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Care
Arm Type
No Intervention
Arm Description
Standard care
Arm Title
Heparin
Arm Type
Experimental
Arm Description
Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days
Intervention Type
Drug
Intervention Name(s)
Nebulised heparin
Intervention Description
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days
Primary Outcome Measure Information:
Title
D-dimer profile
Description
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.
Time Frame
Up to day 10.
Title
Frequenccy of Severe Adverse Outcomes
Description
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.
Time Frame
Up to day 60
Secondary Outcome Measure Information:
Title
Oxygenation Index
Description
Determine the impact of nebulised heparin on oxygenation index
Time Frame
Up to day 10
Title
Indices of Inflammation
Description
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)
Time Frame
Up to day 10
Title
Ratios of Indices of Inflammation
Description
Effect of nebulised heparin on the ratios of IL-1β/IL-10 and IL-6/IL-10 will also be assessed.
Time Frame
Up to day 10
Title
Indices of Coagulation
Description
Effect of nebulised heparin on other indices of coagulation (Fibrinogen; lactate dehydrogenase) will be assessed (AUC on days 1, 3, 5 and 10).
Time Frame
Up to day 10
Title
Quasi-Static Lung Compliance
Description
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 Frame
Up to day 10
Title
Time to separation from advanced respiratory support
Description
Time to separation from advanced respiratory support, where non survivors are treated as though not separated from advanced respiratory support.
Time Frame
Up to day 28
Title
Number treated with neuromuscular blockers
Description
Number treated with neuromuscular blockers instituted after enrolment
Time Frame
Up to day 10
Title
Number treated with Prone positioning
Description
Number treated with prone positioning instituted after enrolment
Time Frame
Up to day 10
Title
Number treated with extra-corporeal membrane oxygenation
Description
Number treated with extra-corporeal membrane oxygenation instituted after enrolment
Time Frame
Up to day 10
Title
Number requiring Tracheostomy
Description
Number tracheotomised
Time Frame
Up to day 28
Title
Time to separation from invasive ventilation among survivors
Description
Time to separation from invasive ventilation among survivors
Time Frame
Up to day 28
Title
Discharge to ward
Description
Time to separation from the ICU to day 28, where non-survivors to day 28 are treated as though not separated from invasive care
Time Frame
Up to day 28
Title
Discharge to ward in survivors
Description
Time to discharge from the ICU to day 28, among survivors
Time Frame
Up to day 28
Title
Patient Survival
Description
Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60
Time Frame
Up to day 60
Title
Number of patients residing at home or in a community setting at day 60
Description
Number residing at home or in a community setting at day 60
Time Frame
Up to day 60
Title
Number of surviving patients residing at home or in a community
Description
Number residing at home or in a community setting at day 60, among survivors
Time Frame
Up to day 60
Title
Ventilatory ratio
Description
Effect of nebulised heparin on ventilatory ratio measured every 6 hours
Time Frame
Up to day 10
Title
Number treated with awake prone positioning
Description
Number of patients treated with awake prone positioning
Time Frame
Up to day 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
APTT > 100 seconds
Platelet count < 50 x 109 per L
Pulmonary bleeding, which is frank bleeding in the trachea, bronchi or lungs with repeated haemoptysis or requiring repeated suctioning
Uncontrolled bleeding
Pregnant or suspected pregnancy (Urine or serum HCG will be recorded)
Receiving or about to commence ECMO or HFOV
Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
Usually receives home oxygen
Dependent on others for personal care due to physical or cognitive decline (pre-morbid status)
Death is imminent or inevitable within 24 hours
The clinical team would not be able to set up the study nebuliser and ventilator circuit as required including with active humidification
Clinician objection.
The use or anticipated use of nebulised tobramycin during this clinical episode
Any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here
Relapse in clinical condition in patient that had fully weaned from advanced respiratory support
Any systemic anticoagulation other than prophylactic anticoagulation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Laffey
Phone
+353 91 544074
Email
John.laffey@nuigalway.ie
First Name & Middle Initial & Last Name or Official Title & Degree
David Cosgrave
Phone
+35391544074
Email
davidw.cosgrave@hse.ie
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Laffey
Organizational Affiliation
Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Galway
City
Galway
Country
Ireland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Cosgrave, MDBChBAOFCAI
Email
davidw.cosgrave@hse.ie
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Investigator will consider requests to share anonymised data for the purposes of meta-analysis following discussion with the sponsor.
IPD Sharing Time Frame
Investigator will consider release of the above data once the study report has been completed.
IPD Sharing Access Criteria
To be confirmed, prior to enrollment of the first patient.
Citations:
PubMed Identifier
36104785
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.
Results Reference
derived
Learn more about this trial
Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury
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