Covid19Phase 1/2CHARTER-IrlNCT04511923
Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury
A Phase 1/2 study testing Nebulised heparin in people with Covid19 and ARDS, Human, run by University College Hospital Galway at 1 site in Ireland.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, ARDS, Human, Lung Injury, Acute
- What is being tested?
- Nebulised heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteIreland
- Study dates
- 23 Dec 2020to 28 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland
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.
- Being tested
- Nebulised heparin
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nebulised heparinDrug
Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Standard Care | No intervention | Standard care |
| Heparin | Experimental | Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days Receives: Drug: Nebulised heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to day 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.
Measured: Up to day 60
Secondary outcomes (18)
Oxygenation Index
Determine the impact of nebulised heparin on oxygenation index
Measured: Up to day 10
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)
Measured: Up to day 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.
Measured: Up to day 10
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).
Measured: Up to day 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.
Measured: Up to day 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.
Measured: Up to day 28
Number treated with neuromuscular blockers
Number treated with neuromuscular blockers instituted after enrolment
Measured: Up to day 10
Number treated with Prone positioning
Number treated with prone positioning instituted after enrolment
Measured: Up to day 10
Number treated with extra-corporeal membrane oxygenation
Number treated with extra-corporeal membrane oxygenation instituted after enrolment
Measured: Up to day 10
Number requiring Tracheostomy
Number tracheotomised
Measured: Up to day 28
Time to separation from invasive ventilation among survivors
Time to separation from invasive ventilation among survivors
Measured: Up to day 28
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
Measured: Up to day 28
Discharge to ward in survivors
Time to discharge from the ICU to day 28, among survivors
Measured: Up to day 28
Patient Survival
Survival to day 28; Survival to day 60; and Survival to hospital discharge, censored at day 60
Measured: Up to 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
Measured: Up to 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
Measured: Up to day 60
Ventilatory ratio
Effect of nebulised heparin on ventilatory ratio measured every 6 hours
Measured: Up to day 10
Number treated with awake prone positioning
Number of patients treated with awake prone positioning
Measured: Up to day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2020
- Study start23 Dec 2020
- Primary completion31 Dec 2021
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College Hospital Galway
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Laffey, University College Hospital Galway
- Investigators
- John Laffey, Principal investigator, Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04511923
- Sponsor's protocol ID
- NUIG-2020-003
- Acronym
- CHARTER-Irl
- Status last verified
- Jul 2024
- First submitted
- 10 Aug 2020
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Investigator will consider requests to share anonymised data for the purposes of meta-analysis following discussion with the sponsor.
Publications
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.
PubMed 36104785
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland
- ClinicalTrials.gov ID
- NCT04511923
- Acronym / sponsor ID
- CHARTER-Irl / NUIG-2020-003
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University College Hospital GalwayUniversity, hospital or other
- Study start
- 23 Dec 2020 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 13 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Care | No intervention | –Standard care |
| Heparin | Experimental | Drug: Nebulised heparinStandard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nebulised heparinNebulised unfractionated heparin 25000 units administered 6 hourly for 10 days | Drug | Heparin |
Primary outcome
D-dimer profile
Time frame: 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
Time frame: 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.
18 secondary outcomes
Oxygenation Index
Time frame: Up to day 10
Indices of Inflammation
Time frame: Up to day 10
Ratios of Indices of Inflammation
Time frame: Up to day 10
Indices of Coagulation
Time frame: Up to day 10
Quasi-Static Lung Compliance
Time frame: Up to day 10
Time to separation from advanced respiratory support
Time frame: Up to day 28
Number treated with neuromuscular blockers
Time frame: Up to day 10
Number treated with Prone positioning
Time frame: Up to day 10
Number treated with extra-corporeal membrane oxygenation
Time frame: Up to day 10
Number requiring Tracheostomy
Time frame: Up to day 28
Time to separation from invasive ventilation among survivors
Time frame: Up to day 28
Discharge to ward
Time frame: Up to day 28
Discharge to ward in survivors
Time frame: Up to day 28
Patient Survival
Time frame: Up to day 60
Number of patients residing at home or in a community setting at day 60
Time frame: Up to day 60
Number of surviving patients residing at home or in a community
Time frame: Up to day 60
Ventilatory ratio
Time frame: Up to day 10
Number treated with awake prone positioning
Time frame: Up to day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
- Derived from this study: PubMed 36104785Sheehan 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.
- Individual participant dataSharing planned: Yes. Investigator will consider requests to share anonymised data for the purposes of meta-analysis following discussion with the sponsor.
Related trials for Covid19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Laffey principal investigator
Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nebulised heparin in people with Covid19 and ARDS, Human, run by University College Hospital Galway at 1 site in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
D-dimer profile (time frame: Up to day 10.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04511923, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.