Clinical trial NCT04545541: Nebulised Heparin in Patients With Severe COVID-19
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Covid19
Respiratory Failure
Keywords: COVID19; ARDS; mortality; clinical trial; metaanalysis; PRCT
Lead sponsor: Australian National University
Sponsor class: OTHER
First posted: 2020-09-11
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Alive and Ventilator Free Score
timeFrame: Day 28
Secondary outcomes:
Other outcomes:
Locations:
city: Frederick
country: United States
facility: Frederick Health Hospital
state: Maryland
Study officials:
affiliation: Australian National University
name: Frank MP van Haren, MD, PhD
role: STUDY_CHAIR
References:
citation: van Haren FMP, Page C, Laffey JG, Artigas A, Camprubi-Rimblas M, Nunes Q, Smith R, Shute J, Carroll M, Tree J, Carroll M, Singh D, Wilkinson T, Dixon B. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Crit Care. 2020 Jul 22;24(1):454. doi: 10.1186/s13054-020-03148-2.