A Phase II, Randomised, Double-blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 170
- 试验地点
- 30
- 主要终点
- Clinical Improvement by Day 14
研究概览
简要总结
The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.
详细描述
The ARCADIA Trial will assess the safety and efficacy of AZD1656 in 150 patients with either Type 1 or Type 2 diabetes who have been hospitalised with COVID-19.
AZD1656 is a glucokinase (GK; hexokinase 4) activator which has been shown to reduce blood glucose for up to 4 months in humans. Diabetic patients admitted to hospital with COVID-19 often present with hyperglycaemia and are particularly vulnerable to progression to severe COVID-19. Treatment with AZD1656 (in addition to their usual care) may provide additional glucose control which could help improve clinical outcomes in both Type 1 and Type 2 diabetic populations.
In addition to its glucose lowering effect, AZD1656 may have additional benefits to COVID-19 patients via its effects on immune function. In many patients with severe COVID-19, an overreaction of the body's own immune system can cause severe problems including damage to the lungs and heart, which can lead to breathing problems necessitating intubation and ventilation. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017)). AZD1656 could enhance Treg migratory capacity and may prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19, leading to lower requirements for oxygen therapy and assisted ventilation, and reduced incidences of pneumonia and acute respiratory distress syndrome (ARDS).
Diabetic patients hospitalised with COVID-19 will be randomised to receive either AZD1656 tablets or placebo tablets on a 1:1 basis until they are discharged from hospital or until they require intubation/mechanical ventilation. The aim of the study is to determine whether AZD1656 improves clinical outcomes in diabetic patients hospitalised with COVID-19. The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement will be used as the standard methodology for measuring patient 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 (Participant, Investigator)
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
- •Male or Female.
- •Aged 18 and older.
- •Have either Type I or Type II Diabetes Mellitus.
- •Hospitalised with suspected or confirmed novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) infection at time of enrolment, categorised as stage 3, 4 or 5 on the WHO Ordinal Scale for Clinical Improvement.
- •Blood glucose level at or above 4 mmol/L.
- •Able to take oral (tablet) formulation of medication.
- •Patient is able to provide written informed consent prior to initiation of any study procedures.
排除标准
- •In the opinion of the clinical team, progression to intubation or mechanical ventilation is imminent and inevitable, within the next 24 hours, irrespective of the provision of treatments.
- •Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.
- •Treatment with immunomodulators or anti-rejection drugs within the last 3 months.
- •Pregnant or breast feeding.
- •Men, and women of child-bearing potential, unwilling to use highly effective contraception during their participation in the trial and for 2 weeks after study completion.
- •Anticipated transfer to another hospital which is not a study site within 72 hours.
- •Known sensitivity to any of the study medication/placebo excipients.
- •Prior dosing with AZD1656 on a previous clinical trial.
- •Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.
- •Any known non-COVID-19, non-diabetes related, serious condition which, in the opinion of the clinical team, makes the patient unsuitable for the trial.
- •Known history of drug or alcohol abuse within previous 12 months of screening.
- •Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.
- •Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C
- •Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product (IMP) containing small molecule treatment(s) within 30 days or 5 half-lives (whichever is longer) prior to enrolment into this study, or containing biological treatment(s) within 3 months prior to entry into this study.
研究组 & 干预措施
AZD1656 (plus Usual Hospital Care)
50mg film-coated tablets at a dose of 100mg BID
干预措施: AZD1656 (Drug)
Matched Placebo (plus Usual Hospital Care)
Matched placebo tablets
干预措施: Placebo (Other)
结局指标
主要结局
Clinical Improvement by Day 14
时间窗: Day 1 to Day 14
The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 14 versus baseline, comparing AZD1656 treatment with placebo. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient. Results are presented as number of responders. Patients who were assigned a WHO score of 1, 2 or 3 at Day 14 were considered a treatment responder. A patient who was discharged before Day 14 was also considered a responder. All other patients (WHO scores 4-8 at Day 14) were considered treatment failures.
次要结局
- Clinical Improvement at Day 7, 14 and 21(Day 1 to Day 21)
- Glycaemic Control(Day 1 to Day 21)
- Intubation/Mechanical Ventilation(Day 1 to Day 21)
- Occurrence of Adverse Events(Day 1 to Day 28)
- Duration of Hospitalisation(Day 1 to Day 21)
- Occurrence of Serious Adverse Events(Day 1 to Day 28)
- Mortality Rate(Day 1 to Day 28)