Can Nebulised HepArin Reduce acuTE Lung Injury in Patients With SARS-CoV-2 Requiring Respiratory Support in Ireland
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Frequenccy of Severe Adverse Outcomes
研究概览
简要总结
The investigators present a randomised open label phase Ib/IIa trial of nebulised unfractionated heparin to evaluate the effect of nebulised unfractionated heparin on the procoagulant response in ICU patients with SARS-CoV-2 requiring advanced respiratory support. As this is one of the first studies of nebulised heparin in COVID 19 lung disease the investigators will assess safety as a co-primary outcome.
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
- None
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
- •To be eligible, a patient must satisfy all these inclusion criteria:
- •Confirmed or suspected COVID-
- •Note, if 'suspected', results must be pending or testing intended
- •Ability to obtain informed consent/assent to participate in study
- •Age 18 years or older
- •Requiring high flow nasal oxygen or positive pressure ventilator support or invasive mechanical ventilation for a time period of no greater than 48 hours
- •D-dimers > 200 ng/ml
- •PaO2 to FIO2 ratio less than or equal to 300
- •Acute opacities on chest imaging affecting at least one lung quadrant. Note 'Acute opacities' do not include effusions, lobar/lung collapse or nodules
- •Currently in a higher level of care area designated for inpatient care of patients where therapies including non-positive pressure ventilatory support can be provided.
- •Exclusion criteria
- •To be eligible, a patient must have none of these exclusion criteria:
- •Enrolled in another clinical trial that is unapproved for co-enrolment
- •Heparin allergy or heparin-induced thrombocytopaenia
- •APTT > 100 seconds
- •Platelet count < 50 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 suspected pregnancy (Urine or serum HCG will be recorded)
- •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
- •Usually receives home oxygen
- •Dependent on others for personal care due to physical or cognitive decline (pre-morbid status)
- •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.
- •The use or anticipated use of nebulised tobramycin during this clinical episode
- •Any other specific contraindication to anticoagulation including prophylactic anticoagulation not otherwise listed here
- •Relapse in clinical condition in patient that had fully weaned from advanced respiratory support
- •Any systemic anticoagulation other than prophylactic anticoagulation
排除标准
- 未提供
研究组 & 干预措施
Heparin
Standard care plus nebulised unfractionated heparin 25000 units every 6 hours for 10 days
干预措施: Nebulised heparin (Drug)
结局指标
主要结局
Frequenccy of Severe Adverse Outcomes
时间窗: Up to day 60
Safety of nebulised heparin delivered by aerogen solo nebuliser in patients with COVID-19 induced severe respiratory failure, as measured by the incidence of severe adverse events.
D-dimer profile
时间窗: Up to day 10.
Effect of nebulised heparin on d-dimer profile, assessed via d-dimer AUC and via a mixed effects model, with data collected on days 1, 3, 5 and 10.
次要结局
- Oxygenation Index(Up to day 10)
- Ratios of Indices of Inflammation(Up to day 10)
- Time to separation from advanced respiratory support(Up to day 28)
- Indices of Inflammation(Up to day 10)
- Number treated with Prone positioning(Up to day 10)
- Number treated with extra-corporeal membrane oxygenation(Up to day 10)
- Discharge to ward in survivors(Up to day 28)
- Patient Survival(Up to day 60)
- Number of surviving patients residing at home or in a community(Up to day 60)
- Number treated with awake prone positioning(Up to day 10)
- Indices of Coagulation(Up to day 10)
- Number treated with neuromuscular blockers(Up to day 10)
- Discharge to ward(Up to day 28)
- Number of patients residing at home or in a community setting at day 60(Up to day 60)
- Quasi-Static Lung Compliance(Up to day 10)
- Number requiring Tracheostomy(Up to day 28)
- Time to separation from invasive ventilation among survivors(Up to day 28)
- Ventilatory ratio(Up to day 10)
研究者
John Laffey
Professor, Anaesthesia and Intensive Care Medicine, School of Medicine, NUI Galway; Consultant, Anaesthesia and ICM, Galway University Hospitals; Vice-Dean Research, College of Medicine, Nursing
University College Hospital Galway