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Nebulised Heparin in Patients With Severe COVID-19 (CHARTER-MT)

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ClinicalTrials.gov Identifier: NCT04545541
Recruitment Status : Recruiting
First Posted : September 11, 2020
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Frank van Haren, Australian National University

Brief Summary:

The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospective collaborative individual patient data analysis of randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries, including Australia, Ireland, the USA, and the UK.

Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2 infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant on chest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours or standard care (open label studies) or placebo (blinded placebo controlled studies) for up to 10 days while mechanically ventilated. All trials will collect a minimum core dataset. The primary outcome for the meta-trial is ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Individual studies may have additional outcomes.


Condition or disease Intervention/treatment Phase
Covid19 Respiratory Failure Drug: Nebulised unfractionated heparin (UFH) Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Can Nebulised HepArin Reduce morTality and Time to Extubation in Patients With COVID-19 Requiring Mechanical Ventilation Meta-Trial (CHARTER-MT): Protocol for an Investigator-initiated International Meta-trial of Randomised Studies
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Nebulised heparin
Participants assigned to "nebulised UFH" will receive nebulised UFH in addition to the standard care required as determined by the treating team. Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days.
Drug: Nebulised unfractionated heparin (UFH)
Nebulised UFH (25,000 Units in 5 mL) will be administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days.

No Intervention: Control group

Participants assigned to 'standard care' will receive the standard care required as determined by the treating team and will not be treated with nebulised heparin (Australia, Ireland).

Participants assigned to "placebo" will receive Nebulised 0.9% Sodium Chloride (5 mL) administered 6-hourly via an Aerogen Solo vibrating mesh nebuliser while patients receive invasive mechanical ventilation in ICU and for a maximum of 10 days (USA).




Primary Outcome Measures :
  1. Alive and Ventilator Free Score [ Time Frame: Day 28 ]
    Validated hierarchical composite endpoint, based on mortality and ventilator free days, which is less prone to favour a treatment with discordant effects on survival and days free of ventilation.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Currently in an intensive care unit (ICU) or scheduled for transfer to the ICU. During the pandemic, critically ill inpatients might be cared for outside of the walls of the usual physical environment of ICU. For this reason, ICU is defined as an area designated for inpatient care of the critically ill where therapies including invasive mechanical ventilation can be provided.
  • Endotracheal tube in place
  • Intubated yesterday or today
  • PaO2 to FIO2 ratio less than or equal to 300 while intubated
  • Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least one lung quadrant on chest X-ray or CT
  • The acute opacities on chest X-ray or CT are most likely due to COVID-19
  • There is a PCR positive sample for SARS-CoV-2 within the past 21 days or there are results pending or further testing is planned. The sample can be a nasal or pharyngeal swab, sputum, tracheal aspirate, bronchoalveolar lavage, or another sample from the patient.

Exclusion Criteria:

  • Enrolled in another clinical trial that is unapproved for co-enrolment
  • Heparin allergy or heparin-induced thrombocytopaenia (HIT)
  • APTT > 120 seconds and this is not due to anticoagulant therapy
  • Platelet count < 20 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 might be pregnant. Females aged 18-49 years are excluded unless there is documented menopause or hysterectomy or a pregnancy test was performed and is negative.
  • Receiving or about to commence extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)
  • Myopathy, spinal cord injury, or nerve injury or disease with a likely prolonged incapacity to breathe independently e.g. Guillain-Barre syndrome
  • Acute brain injury that may result in long-term disability
  • Usually receives home oxygen
  • Dependent on others for personal care due to physical or cognitive decline
  • 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
  • Refusal of participant (person responsible) consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04545541


Contacts
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Contact: Frank MP van Haren, MD, PhD +61467051809 fvanharen@me.com

Locations
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United States, Maryland
Frederick Health Hospital Recruiting
Frederick, Maryland, United States, 21701
Contact: Thomas Smoot, PharmD BCPS    240-566-3250    tsmoot@fmh.org   
Sponsors and Collaborators
Australian National University
Investigators
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Study Chair: Frank MP van Haren, MD, PhD Australian National University
Publications:
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Responsible Party: Frank van Haren, Associate Professor, Australian National University
ClinicalTrials.gov Identifier: NCT04545541    
Other Study ID Numbers: CHARTER meta-trial
First Posted: September 11, 2020    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The CHARTER-MT Collaborative Research Group's executive committee, with representatives from each individual country/trial, is responsible for the meta-trial's study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Investigators from individual trials have ownership of their trial data. A memorandum of understanding and data sharing agreement between investigators will facilitate and govern the pooling and meta-analysing of de-identified individual patient data from individual trials, as well as outline authorship.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Real-time

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Frank van Haren, Australian National University:
COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT
Additional relevant MeSH terms:
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COVID-19
Respiratory Insufficiency
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Heparin
Calcium heparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action