Phase II Study of Heme Arginate in Patients Planned for Cardiac Surgery
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Upregulation of Heme oxygenase-1 protein expression in circulating monocytes
研究概览
简要总结
A recent analysis of over 4500 cardiac surgical patients at the Royal Infirmary of Edinburgh has confirmed that acute kidney injury (AKI) is not only a relatively common post-operative complication but is associated with prolonged hospital stay, and increased risk of death. There is currently no specific therapy available except supportive care.
In laboratory studies, heme arginate (HA), a drug licensed for human use, has been shown to upregulate the anti-inflammatory enzyme hemeoxygenase-1 (HO-1) and protect aged mice from acute kidney injury.
This study will bring this research into the human arena. It will aim to evaluate the minimum effective dose of HA and verify its safety in this specific group of patients. This will be the next step in investigating if HA could be a potential protective treatment for reducing AKI in patients about to have cardiac surgery.
Patients who are due to have cardiac surgery and are aged 60 or above will be approached for inclusion in the study. If agreeable, they will be randomly assigned to receive either HA at a dose of 1mg/kg or 3mg/kg. There will be 10 patients in each group.
Blood tests will be taken just before the study drug is given, at 6 hours, 24 hours and 7 days post dose. These samples will be used to examine the effect of HA on HO-1 at different doses, and will verify drug safety. Any adverse effects of the drug will be evaluated, although HA has an excellent safety profile when used as it is currently licensed for acute porphyria. Urine samples will also be collected to assess inflammation and quantify urinary biomarkers of AKI. This will set the scene for a randomised clinical trial of HA in cardiac surgical patients at high risk of AKI.
详细描述
AKI is a common condition which carries significant morbidity and mortality and has no current treatment except supportive care.
Cardiac surgery remains the standard of care for the revascularisation of the most severe coronary artery disease despite improvements in percutaneous coronary intervention. The nature of such surgery confers an ischaemic renal insult and it follows on that AKI is a relatively common complication. However, the reported incidence of AKI post cardiac surgery varies widely depending on the diagnostic criteria used. A recent retrospective analysis of 4572 cardiac surgical patients at the Royal Infirmary of Edinburgh over a 5 year period showed that 12.4% developed AKI by AKIN criteria post operatively. This was associated with an increased risk of death and prolonged inpatient stay.
Pre-clinical studies in murine models of ischaemia reperfusion injury (IRI) have demonstrated that the anti-inflammatory enzyme HO-1 is of interest as a potential target for therapeutic intervention. Heme arginate (HA) is a drug licensed for human use, as a treatment for acute porphyria. HA upregulates HO-1, and ameliorates IRI when given before injury in murine models of IRI. In Phase I clinical trials, HA has been shown to upregulate HO-1 and is well tolerated.
This is a single-blinded randomised trial of Heme arginate (HA) in patients who are due to have cardiac surgery. The aim of the study is to investigate the efficacy of HA in HO-1 upregulation and its safety in this patient cohort. This will inform a further clinical trial of HA as a preventative treatment for AKI in patients undergoing cardiac surgery.
Methods
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Planned for elective cardiac surgical procedure:
- •Aortic valve replacement
排除标准
- •Inability to give informed consent Hypersensitivity to HA Enrolment in other clinical trials Renal replacement therapy Planned for elective cardiac surgical procedure other than CABG or AVR (including combined CABG and AVR) Less than 2 weeks until planned cardiac surgery at time of study drug administration Active infection
研究组 & 干预措施
Heme arginate 1mg/kg
This is the lower of the 2 doses of Heme arginate (HA). This will be given as a single dose of 1mg/kg on the first study visit.
This is given over 1 hour intravenously.
干预措施: Heme arginate (Drug)
Heme arginate 3mg/kg
This is the larger dose, Heme arginate 3mg/kg (up to a maximum dose of 250mg)
This will be given intravenously, as a single dose on the first study visit, over one hour.
干预措施: Heme arginate (Drug)
结局指标
主要结局
Upregulation of Heme oxygenase-1 protein expression in circulating monocytes
时间窗: within 3 months of study completion
次要结局
- Upregulation of heme oxygenase-1 messenger ribonucleic acid (mRNA) in circulating monocytes(within 3 months of completion)
- Urinary biomarkers of acute kidney injury(within 3 months of completion of study)
- Safety(at final study visit ie 7 days post dose (or at the resolution of any ongoing adverse event if this lasts longer than 7 days))
- Heme oxygenase-1 (HO-1) Genotype(within 3 months of study completion)