An Open Non-comparative Study of the Efficacy and Safety of Aprotinin in Patients Hospitalized With COVID-19
试验速览
- 阶段
- 不适用
- 发起方
- Aviron LLC
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Time to D-dimer normalization
研究概览
简要总结
The observational study will be carried out in two stages. At the first stage, the efficacy and safety of Aprotinin intravenous infusion as add-on therapy to the standard of care will be studied. At the second stage, two groups will be included: the first group will be the inhaled Aprotinin add-on therapy, the second group will be intravenous Aprotinin in combination with Favipiravir.
详细描述
Primary objective of the study is to evaluate the efficacy of Aprotinin as add-on therapy in patients hospitalized with COVID-19 using the following parameters:
- The time to elimination of SARS-CoV-2 virus until Day 10;
- The time to C-reactive protein (CRP) normalization until Day 10;
- The time to D-dimer normalization until Day 10.
Secondary objectives are to evaluate the following parameters of efficacy and safety of Aprotinin add-on therapy in patients hospitalized with COVID-19:
- The time to body temperature normalization (<37oC);
- Changes from baseline of the laboratory parameters during 14 days: hematology, CRP, coagulogram;
- Changes of lung injury on CT scan on Day 7 and Day 14 from baseline;
- Frequency of clinical status improvement by 2 scores in accordance with the WHO Ordinal scale of clinical improvement (WHO-OSCI) or discharge from the hospital before Day 14;
- Frequency of transfer to the Intensive Care Unit (ICU), frequency of the non-invasive ventilation, frequency of the invasive ventilation and mortality rate;
- Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) of various severity according to subjective complains, physical examination, vital signs, laboratory tests and ECG.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Signed Patient Information Sheet and Informed Consent Form for participation in the study;
- •Adult male or female ≥18 years of age;
- •Body mass < 90 kg;
- •Positive qualitative RNA SARS-CoV-2 PCR analysis at screening;
- •Score 4 on the WHO-OSCI (added at Stage 2);
- •Subjects with moderate-to-severe disease with the follow conditions and symptoms:
- •Pneumonia;
- •Fever > 38°C;
- •Blood serum CRP > 10 mg/L.
- •Agreement to use medically acceptable forms of birth control during the study (contraceptive with spermicide).
排除标准
- •Severe disease with one of the follow criteria:
- •Respiratory rate > 35 per minute that doesn't decrease after body temperature reducing to normal or subfebrile level;
- •Saturation ≤ 93% at rest;
- •Partial pressure of arterial oxygen (PaO2) < 60 mmHg;
- •Oxygenation index (РаО2/FiO2) ≤ 200 mmHg;
- •Partial pressure of arterial CO2 (PaCO2) > 60 mmHg;
- •Septic shock.
- •Chronic liver and kidney diseases in terminal stage;
- •Other organs failure requiring control and treatment in the ICU;
- •Subjects with HIV;
- •Using of Aprotinin during 6 months prior to screening; hypersensitivity to any of the drug components;
- •Participation in any other clinical trial or using of other study drugs during 28 days prior to screening;
- •Pregnant or lactating women or women planning pregnancy during the clinical study; women with child-bearing potential (including women non-sterilized surgically and in postmenopause for less than 2 years) not using medically acceptable forms of birth control;
- •Inability to read or write; unwillingness to understand and follow the Protocol procedures; non-compliance with the regimen of taking medications or performing procedures that, according to the Investigator, may affect the results of the study or the safety of the patient and prevent the patient from further participation in the study; any other comorbid medical or serious mental conditions that make patient ineligible for participation in the clinical study, limits the ability to obtain informed consent, or may affect patient's ability to participate in the study.
研究组 & 干预措施
Stage 1/Group 1
Intravenous Aprotinin in addition to standard care: 1 000 000 KIU IV daily during 3 days
干预措施: Aprotinin (Drug)
Stage 2/Group 2
Inhaled Aprotinin in addition to standard care: 625 KIU 4 times per day during 5 days
干预措施: Aprotinin (Drug)
Stage 2/Group 3
Intravenous Aprotinin in addition to standard care that includes Favipiravir: 1 000 000 KIU IV daily during 5 days
干预措施: Aprotinin (Drug)
结局指标
主要结局
Time to D-dimer normalization
时间窗: 10 days
Time to D-dimer \<243 ng/mL \[days\]
Time to elimination of SARS-CoV-2 virus
时间窗: 10 days
Time to two negative PCR tests with at least 24 hours interval \[days\]
Time to CRP normalization
时间窗: 10 days
Time to CRP \<10 mg/L \[days\]
次要结局
- Time to body temperature normalization(14 days)
- Change in absolute neutrophil count (ANC)(Baseline to Day 14)
- Change of D-dimer(Baseline to Day 14)
- Change in fibrinogen(Baseline to Day 14)
- Change of Quick's value(Baseline to Day 14)
- Change of international normalized ratio (INR)(Baseline to Day 14)
- Changes of lung injury on CT scan(Baseline to Day 14)
- Frequency of clinical status improvement by 2 scores in accordance with the WHO-OSCI or discharge from the hospital(14 days)
- Frequency of deterioration of the patients' status(14 days)
- Frequency of AEs and SAEs(14 days)
- Change in white blood cells (WBC)(Baseline to Day 14)
- Change of CRP(Baseline to Day 14)