Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury

NCT04511923 | Completed Phase 1 DMC

• 1 other identifier: NUIG-2020-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (18)

• Oxygenation Index

  Up to day 10

• Indices of Inflammation

  Up to day 10

• Ratios of Indices of Inflammation

  Up to day 10

• Indices of Coagulation

  Up to day 10

• Quasi-Static Lung Compliance

  Up to day 10

Study Arms (2)

Standard Care

NO INTERVENTION

Standard care

Heparin

EXPERIMENTAL

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

Drug: Nebulised heparin

Interventions

Nebulised heparin DRUG

Nebulised unfractionated heparin 25000 units administered 6 hourly for 10 days

Heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University College Hospital Galway: lead

Study Sites (1)

University Hospital Galway

Galway, Ireland

Location

Related Publications (1)

• 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.

  PMID: 36104785 DERIVED

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Acute Lung Injury

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury

Study Officials

• John Laffey

  Professor of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Anaesthesia and Intensive Care Medicine, School of Medicine, NUI Galway; Consultant, Anaesthesia and ICM, Galway University Hospitals; Vice-Dean Research, College of Medicine, Nursing

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: August 13, 2020
• Study Start: December 23, 2020
• Primary Completion: December 31, 2021
• Study Completion: February 28, 2022
• Last Updated: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Investigator will consider release of the above data once the study report has been completed.
• Access Criteria: To be confirmed, prior to enrollment of the first patient.

Locations

IE (1)