A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Time course of body temperature (fever)
研究概览
简要总结
This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted.
详细描述
This is a small pilot study investigating whether there is any efficacy signal that warrants a larger Phase 2B trial, or any harm that suggests that such a trial should not be done. It is not expected to produce statistically significant results in the major endpoints. The investigators will examine all of the biologic, physiological, and clinical data to determine whether a Phase 2B trial is warranted.
Primary efficacy analysis will be carried only on patients receiving at least 4 doses of active drug. Safety analysis will be carried out on all patients receiving at least one dose of active drug.
It is planned to enroll more than or equal to 24 subjects with COVID-19. It is expected to have at least 12 evaluable patients in each group.
Experimental group: 0.4 mg/kg rhACE2 IV BID and standard of care Control group: standard of care
Intervention duration: up to 7 days of therapy
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Laboratory diagnosis:
- •Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR; OR,
- •The viral gene sequencing of the respiratory specimen is highly homologous to known novel coronavirus.
- •Axillary temperature >37.3℃
- •Respiratory variables (meets one of the following criteria):
- •Respiratory rate: RR ≥25 breaths/min
- •Oxygen saturation ≤93% at rest on room air
- •PaO2/FiO2 ≤300 mmHg（1 mmHg=0.133 KPa）
- •Pulmonary imaging showed that the lesions progressed more than 50% within 24-48 hours, and the patients were managed as severe
- •HBsAg negative, or HBV DNA ≤10^4 copy/ml if HBsAg positive; anti-HCV negative; HIV negative two weeks prior to signed Informed Consent Form (ICF)
- •Appropriate ethics approval and
排除标准
- •Age <18 years; Age >80 years
- •Pregnant or breast feeding woman or with positive pregnancy test result
- •P/F <100 mmHg
- •Moribund condition (death likely in days) or not expected to survive for >7 days
- •Refusal by attending MD
- •Not hemodynamically stable in the preceding 4 hours (MAP ≤65 mmHg, or SAP <90 mmHg, DAP <60 mmHg, vasoactive agents are required)
- •Patient on invasive mechanical ventilation or ECMO
- •Patient in other therapeutic clinical trial within 30 days before ICF
- •Receive any other ACE inhibitors (ACEI), angiotensin-receptor blockers (ARB) treatment within 7 days before ICF
- •Chronic immunosuppression: current autoimmune diseases or patients who received immunotherapy within 30 days before ICF
- •Hematologic malignancy (lymphoma, leukemia, multiple myeloma)
- •Other patient characteristics (not thought to be related to underlying COVID-19) that portend a very poor prognosis (e.g, severe liver failure, and ect)
- •Known allergy to study drug or its ingredients related to renin-angiotensin system (RAS), or frequent and/or severe allergic reactions with multiple medications
- •Other uncontrolled diseases, as judged by investigators
- •Body weight ≥85 kg
研究组 & 干预措施
rhACE2 group
0.4 mg/kg IV BID for 7 days (unblinded) + standard of care
干预措施: Recombinant human angiotensin-converting enzyme 2 (rhACE2) (Drug)
结局指标
主要结局
Time course of body temperature (fever)
时间窗: 14 days
Compare the time course of body temperature (fever) between two groups over time.
Viral load over time
时间窗: 14 days
Compare viral load between two groups over time.
次要结局
- Renin changes over time(14 days)
- Angiotensin-converting enzyme (ACE) changes over time(14 days)
- Interleukin 6 (IL-6) changes over time(14 days)
- Von willebrand factor (vWF) changes over time(14 days)
- Tumor necrosis factor-α (TNF-α) changes over time(14 days)
- Surfactant protein-D (SP-D) changes over time(14 days)
- Angiopoietin-2 changes over time(14 days)
- P/F ratio over time(14 days)
- Sequential organ failure assessment score(SOFA score) over time(14 days)
- Pulmonary Severity Index (PSI)(14 days)
- Angiotensin II (Ang II) changes over time(14 days)
- C-reactive protein levels over time(14 days)
- Image examination of chest over time(14 days)
- Proportion of subjects who progressed to critical illness or death(14 days)
- Time from first dose to conversion to normal or mild pneumonia(14 days)
- T-lymphocyte counts over time(14 days)
- Angiotensin 1-7 (Ang 1-7) changes over time(14 days)
- Angiotensin 1-5 (Ang 1-5) changes over time(14 days)
- Aldosterone changes over time(14 days)
- Interleukin 8 (IL-8) changes over time(14 days)
- Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time(14 days)
- Plasminogen activator inhibitor type-1 (PAI-1) changes over time(14 days)
- Angiotensin-converting enzyme 2 (ACE2) changes over time(14 days)
- Soluble receptor for advanced glycation end products (sRAGE) changes over time(14 days)
- Frequency of adverse events and severe adverse events(14 days)
研究者
Yimin LI
Director Physician
The First Affiliated Hospital of Guangzhou Medical University