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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Alive and Ventilator Free Score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Nebulised unfractionated heparin (UFH) (Drug)
结局指标
主要结局
Alive and Ventilator Free Score
时间窗: 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.
次要结局
未报告次要终点
研究者
Frank van Haren
Associate Professor
Australian National University