The Can nebulised HepArin Reduce morTality and time to Extubation in Patients withCOVID-19 Requiring mechanical ventilation Meta-Trial (CHARTER-MT) is a prospectivecollaborative individual patient data analysis of randomised controlled trials and earlyphase studies. Individual studies are being conducted in multiple countries, includingAustralia, Ireland, the USA, and the UK.Mechanically ventilated patients with confirmed or strongly suspected SARS-CoV-2infection, hypoxaemia and an acute pulmonary opacity in at least one lung quadrant onchest X-ray, will be randomised to nebulised heparin 25,000 Units every 6 hours orstandard care (open label studies) or placebo (blinded placebo controlled studies) for upto 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 haveadditional outcomes.
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.
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.
Frederick Health Hospital
Frederick, Maryland, United States
Frank MP van Haren, MD, PhD, Study Chair
Australian National University