ASpirin as a Treatment for ARDS (STAR): a Phase 2 Randomised Control Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 49
- 主要终点
- Oxygenation index (OI)
研究概览
简要总结
Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through their inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. Blood cells called platelets have increasingly been recognized to play a key role in the development of ARDS. There is increasing information that aspirin, a drug which is widely used to treat heart disease, might be important in treating ARDS. We plan to test if aspirin will help in the treatment of ARDS. To do this we will divide patients suffering from ARDS into two groups, one of which will get aspirin and the other a harmless dummy (or placebo) tablet who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if aspirin is effective in patients with ARDS. This project will also provide new information about mechanisms in the development of ARDS leading, potentially, to other new treatments.
详细描述
The role of aspirin as a novel therapy for ARDS.
Aspirin inhibits cyclo-oxygenase enzymes, therefore preventing the formation of lipid mediators including thromboxane A2 (TxA2) and pro-inflammatory prostaglandins from arachidonic acid. TxA2 is required for platelet degranulation and aggregation. Production of pro-inflammatory prostaglandins from arachidonic acid is mediated by cyclo-oxygenase-2 (COX-2), an enzyme induced in inflammatory and endothelial cells by cytokines, growth factors and bacterial products including lipopolysaccharide (LPS). Prostaglandin E2 (PGE2) is a key downstream pro-inflammatory product of COX-2 activation. It can act in an auto and paracrine fashion on local inflammatory and parenchymal cells to increase intracellular cyclic adenosine mono-phosphate (cAMP), drive nuclear translocation of NFκB and thus the production of many pro-inflammatory cytokines, including TNFα and IL-8. Aspirin can also induce the production of a lipoxin (aspirin-triggered 15-epi-lipoxin A4, also known as ATL). Lipoxins are a group of anti-inflammatory eicosanoids derived from arachidonic acid which act via the lipoxin A4 receptor (LXA4R) on leucocytes to inhibit free-radical formation, and reduce activation of the proinflammatory transcription factors AP-1 and NFκB, all of which are implicated in the development of ARDS.
Hypothesis.
Treatment with aspirin is safe and improves important surrogate clinical outcomes in adult patients with ARDS.
Trial objectives.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients receiving invasive mechanical ventilation.
- •ARDS as defined by the Berlin definition.
- •Onset within 1 week of identified insult.
- •Within the same 24 hours
- •Hypoxic respiratory failure (PaO2/ FiO2 ratio ≤ 40kPa on PEEP ≥ 5 cmH20),
- •Bilateral infiltrates on chest X-ray consistent with pulmonary oedema not explained by another pulmonary pathology,
- •No evidence of heart failure or volume overload
排除标准
- •More than 72 hours from the onset of ARDS.
- •Age < 16 years.
- •Patient is known to be pregnant.
- •Participation in a clinical trial of an investigational medicinal product within 30 days.
- •Current treatment with aspirin or within the past 4 weeks.
- •Platelet count < 50 x 109/l.
- •Haemophilia or other haemorrhagic disorder or concurrent therapeutic anticoagulant therapy.
- •History of aspirin sensitive asthma or nasal polyps associated with asthma.
- •Active or history of recurrent peptic ulcer and/ or gastric/ intestinal haemorrhage or other kinds of bleeding such as cerebrovascular haemorrhage.
- •Traumatic brain injury.
- •Active gout.
- •Currently receiving methotrexate.
- •Severe chronic liver disease with Child-Pugh score >
- •Known hypersensitivity or previous adverse reaction to salicylic acid compounds or prostaglandin synthetase inhibitors.
- •Physician decision that aspirin is required for proven indication.
- •Contraindication to enteral drug administration, e.g. patients with mechanical bowel obstruction.
- •Treatment withdrawal imminent within 24 hours.
- •Consent declined.
研究组 & 干预措施
Aspirin 75mg
Aspirin 75mg enterally once daily for a maximum of 14 days
干预措施: Aspirin 75mg (Drug)
Placebo
Lactose powder placebo enterally once daily for a maximum of 14 days
干预措施: Lactose powder (Drug)
结局指标
主要结局
Oxygenation index (OI)
时间窗: Day 7
OI is a physiological index of the severity of ARDS and measures both impaired oxygenation and the amount of mechanical ventilation delivered.
次要结局
- Safety and tolerability as assessed by the occurrence of serious adverse events and suspected unexpected serious adverse reactions(Up to 28 days after completion of study drug)
- Sequential organ failure assessment (SOFA) score(Days 4, 7 and 14)
- Partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (P/F ratio)(Days 4, 7 and 14)
- Oxygenation index(Days 4 and 14)
- Respiratory compliance (Crs)(Days 4, 7 and 14)
研究者
Professor Danny McAuley
Professor and consultant of Intensive Care Medicine
Belfast Health and Social Care Trust