Prospective, Randomised, Double-blind Trial of Icatibant Compared to Placebo in Patients With Early Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Change in Oxygenation
研究概览
简要总结
There is excess accumulation of bradykinin during symptomatic SARS CoV-2 lung infection. Bradykinin causes oedema in the lung, with reduced oxygen. It also causes vasodilation, hypotension and cytokine release.
详细描述
In a normal reaction to a wound, such as after surgery, there is stimulation of pain nerves (called c-fibres), swelling and clotting. When people are hospitalized with COVID-19 they usually have a cough (lung c-fibre stimulation), swelling in the lung and clotting.
Bradykinin is a chemical that is released in response to inflammation. It causes C-fibre stimulation, dilation of vessels with oedema (swelling), lowered blood pressure and release of inflammatory cytokines. Normally the production of bradykinin is carefully balanced in the body. Some people have a tendency to release bradykinin. This results in spontaneous swelling - it is called hereditary episodic angioedema (HAE). There has been a treatment for HAE which has been in use since 2008. It is a medication called Icatibant. This blocks the effect of bradykinin at one of its receptors. It is given by injection under the skin. It has a short half life of approximately 1.5 hours.
The primary aim of the study is to see if treatment with Icatibant will improve blood oxygen levels. COVID-19 patients attending hospital with early symptom onset and low oxygen levels will screened for inclusion in the trial. Patients will be randomly allocated into one of two groups. One group will be given the study drug, Icatibant. The other group will be given a placebo injection containing saline water. Patients and research investigators will be blinded to treatment allocation.
Prior to receiving Icatibant/placebo, patients will have baseline measurements carried out. Blood pressure, Mean arterial pressure, heart rate, oxygen saturations and Fraction of inspired oxygen (FiO2) measurement will be carried out. Patients will undergo an arterial blood gas test. Part of the blood taken will be used for the measurement of interleukin-6 (IL-6) and part will be stored for future use. Patients will also have a retinal photograph of both eyes to assess the retinal vessel size. These measurements will be repeated 3 hours after receiving Icatibant/placebo.
A blood sample will also be taken from a group of control participants who do not have COVID-19 infection. The control blood samples will be analysed for IL-6 and part will also be stored for future use. The results will be compared to the baseline blood sample results taken from the COVID-19 positive trial patients.
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, Care Provider, Investigator)
盲法说明
Patients and investigators will be blinded to treatment allocation. An unblinded research nurse will administer the study medication.
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.
- •Documented evidence of COVID-19 and symptom onset of 7 days or less
- •Acute hypoxia which will be defined as either low resting saturations <94% or supplementary oxygen to maintain oxygen saturations at >94%
排除标准
- •Patients known to be pregnant or breastfeeding.
- •Patients with unstable ischaemic heart disease or acute stroke
- •Patients enrolled in other clinical trials of an investigational medicine within the previous 28 day period
- •Patients who refuse to have blood samples taken.
- •Known hypersensitivity to Icatibant
- •Patients who at time of consent are likely to require imminent non-invasive/ invasive ventilatory support or patients already established on continuous positive airway pressure (CPAP).
- •Patients with chronic heart or lung disease whose oxygen levels are reduced, but are unchanged from baseline
研究组 & 干预措施
Icatibant and Standard of care (SOC)
Icatibant will be given as a single, subcutaneous injection
干预措施: Icatibant (Drug)
0.9% Sodium Chloride and Standard of care (SOC)
Placebo will be given as a single, subcutaneous injection
干预措施: 0.9% Sodium Chloride Injection (Drug)
结局指标
主要结局
Change in Oxygenation
时间窗: Baseline and 3 hours after study drug administration
Alveolar-arterial gradient (Arterial blood gas sampling and FIO2 measurement)
次要结局
- Change in mean arterial pressure (MAP)(Baseline and 3 hours after study drug administration)
- Change in Blood pressure(Baseline and 3 hours after study drug administration)
- Change in heart rate(Baseline and 3 hours after study drug administration)