NCT04545541.

Study name	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
Starting date	1 November 2020
Contact information	Frank MP van Haren, MD, PhD Frederick Health Hospital Frederick, Maryland, USA, 21701 +61467051809 | fvanharen@me.com
Methods	Prospective, multicentre, double‐blinded, 1:1, parallel‐assignment RCT
Participants	300 participants, ≥ 18 years, female and male Inclusion criteria: Age ≥ 18 years Currently in 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 previous or current day PaO2 to FIO2 ratio ≤ 300 while intubated Acute opacities not fully explained by effusions, lobar/lung collapse and nodules, affecting at least 1 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 HIT aPTT > 120 seconds and this is not due to anticoagulant therapy Platelet count < 20 x 109/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. Women 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 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 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 h 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
Interventions	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. Comparator: 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)
Outcomes	Primary Alive and ventilator‐free score (time frame: day 28)
Notes	NCT04545541 | No data provided