Clinical Study to Evaluate the Possible Efficacy and Safety of Antibodies Combination (Casirivimab and Imdevimab) Versus Standard Antiviral Therapy (Remdesivir and Favipravir) as Antiviral Agent Against Corona Virus 2 Infection in Hospitalized COVID-19 Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 265
- 试验地点
- 1
- 主要终点
- 28-days Mortality Rate
研究概览
简要总结
Introduction:
Corona Virus induced disease - 2019 (COVID-19) pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now. With ending of 2021 year, various advances in pharmacotherapy against COVID-19 have emerged.
Regarding antiviral therapy, Casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19. Standard antiviral therapy against COVID-19 includes Remdesivir and Favipravir.
Aim of Study:
- To compare the efficacy of antibodies cocktail (casirivimab and imdevimab), Remdesivir and Favipravir in reducing 28-day mortality in hospitalized patients with moderate, severe or critical COVID19
- To compare safety of antibodies cocktail (casirivimab and imdevimab), Remdesivir and Favipravir by monitoring hypersensitivity and infusion related reactions or other significant adverse effects
Patients and Population:
265 COVID-19 Polymerase Chain Reaction (PCR) confirmed patients with indication for antiviral therapy is included in this study and will be divided into 3 groups (1:2:2):
- Group A: REGN3048-3051(Antibodies cocktail (casirivimab and imdevimab))
- group B: Remdesivir
- group C: Favipravir
Methods:
Study design is single blind non-Randomized Controlled Trial (non-RCT). The drugs of the study are owned by Mansoura University Hospital (MUH), and prescribed by chest diseases lectures of faculty of medicine-Mansoura University. The duration of study is about 6 months after ethical approval.
详细描述
I. INTRODUCTION
1.1. COVID-19 overview and classification
COVID-19 is an infectious viral disease caused by sever acute respiratory syndrome-corona virus 2 (SARS CoV-2) that has affected large number of people all over the world with high mortality rate. COVID-19 infection has been classified as:
- Mild Illness: Individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but who do not have shortness of breath, dyspnea, or abnormal chest imaging.
- Moderate Illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have an oxygen saturation (SpO2) ≥94% on room air at sea level.
- Severe Illness: Individuals who have Saturation pressure of oxygen (SpO2) <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%.
- Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunctions.
Covid-19 pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now. With ending of 2021 year, various advances in pharmacotherapy against COVID-19 have emerged.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age more than 12 years old.
- •weight not less than 40 kg.
- •Moderate, sever or critical COVID-19 disease as defined by WHO.
- •PCR- confirmed patients to be Positive before inclusion.
排除标准
- •history of hypersensitivity or infusion related reactions after administration of monoclonal antibodies.
- •prior use of standard antiviral therapy (remedsvir or favipravir).
- •Current use of controversial antiviral therapy (hydroxychloroquine, ivermectin, nitazoxanide, oseltemavir, acyclovir, ribavirine, lopinvir/rotinvir, sofosfbuvir, decltasevir, semipirvir, azithromycin).
- •patients expected to die within 48 hours.
研究组 & 干预措施
casirivimab and imdevimab
casirivimab and imdevimab, vials 1.2 gm (1200 mg of combined antibodies) diluted in 250 ml 0.9% sodium chloride solution as single I.V infusion over 30-60 minutes.
干预措施: Casirivimab and Imdevimab Drug Combination (Drug)
Remdesivir
Remdesivir, vials Day1 (loading dose): 200 mg (two 100mg vials) diluted in 500ml 0.9% sodium chloride solution infused I.V over 60 minutes Day 2-5 or Day 2-10 (maintenance dose): 100 mg (one 100mg vial) in 250 ml 0.9% sodium chloride solution infused I.V over 30 minutes
干预措施: Remdesivir (Drug)
Favipravir
Favipravir, tablets Day 1 (loading dose): 1600 mg (8 tablets) or 1800 mg (9 tablets) orally or in Ryle tube / 12 hours Day 2-5 or day 2-10 (maintenance dose): 600 mg (3 tablets) or 800 mg (4 tablets) orally or in Ryle tube / 12 hours
干预措施: Favipiravir (Drug)
结局指标
主要结局
28-days Mortality Rate
时间窗: 28 days
Dead or alive
Number of Participants With Positive or Negative Polymerase Chain Reaction (PCR) Test Results at End of Hospital Visit
时间窗: up to 60 days
positive or negative
Number of Participants With Infusion Related Reactions, Hypersensitivity Reactions and Any Serious Adverse Events
时间窗: up to 60 days
yes or no
次要结局
- Albumin at Day 3(day 3)
- Serum Creatinine (S.Cr) at Day 7(day 7)
- Serum Creatinine (S.Cr) at Day 14(day 14)
- Serum Creatinine (S.Cr) at Day 28(day 28)
- Time to Clinical Improvement (Defined as 2 Points Reduction in the WHO Disease Ordinal Progression Scale or Discharge, Whatever Happens First(up to 60 days)
- C-reactive Protein (CRP) at Day 14(day 14)
- Creatine Kinase (Ck) at Day 3(day 3)
- Creatine Kinase (Ck) at Day 7(day 7)
- Need for Invasive Mechanical Ventilation(up to 60 days)
- Oxygen Support Duration (Days)(up to 60 days)
- Duration of Hospitalization(up to 60 days)
- Sequential Organ Function Assessment (SOFA) Score on Day 3(Day 3)
- COVID-19 World Health Organization (WHO) Disease Progression Scale at Day 3(Day 3)
- Aspartate Aminotransferase (AST) at Day 3(day 3)
- Ferritin at Day 3(day 3)
- Lactate Dehydrogenase (LDH) at Day 3(day 3)
- D-dimer at Day 3(day 3)
- Alanine Aminotransferase (ALT) at Day 3(day 3)
- Bilirubin at Day 3(day 3)
- C-reactive Protein (CRP) at Day 7(day 7)
- C-reactive Protein (CRP) at Day 28(day 28)
- Sequential Organ Function Assessment (SOFA) Score on Day 7(day 7)
- C-reactive Protein (CRP) at Day 3(day 3)
- Duration of Intensive Care Unit (ICU) Stay(up to 60 days)
- Sequential Organ Function Assessment Score (SOFA) on Day 14(day 14)
- Sequential Organ Function Assessment Score (SOFA) on Day 28(day 28)
- COVID-19 World Health Organization (WHO) Disease Progression Scale at Day 14(day 14)
- COVID-19 World Health Organization (WHO) Disease Progression Scale at Day 28(day 28)
- Aspartate Aminotransferase (AST) at Day 7(day 7)
- Aspartate Aminotransferase (AST) at Day 14(day 14)
- Aspartate Aminotransferase (AST) at Day 28(day 28)
- COVID-19 World Health Organization (WHO) Disease Progression Scale at Day 7(day 7)
- Alanine Aminotransferase (ALT) at Day 7(day 7)
- Alanine Aminotransferase (ALT) at Day 14(day 14)
- Alanine Aminotransferase (ALT) at Day 28(day 28)
- Bilirubin at Day 7(day 7)
- Bilirubin at Day 14(day 14)
- Bilirubin at Day 28(day 28)
- Albumin at Day 7(day 7)
- Albumin at Day 14(day 14)
- Albumin at Day 28(day 28)
- Platelets at Day 3(day 3)
- Platelets at Day 7(day 7)
- Platelets at Day 14(day 14)
- Platelets at Day 28(day 28)
- Serum Creatinine (S.Cr) at Day 3(day 3)
- D-dimer at Day 7(day 7)
- D-dimer at Day 14(day 14)
- D-dimer at Day 28(day 28)
- Creatine Kinase (Ck) at Day 14(day 14)
- Creatine Kinase (Ck) at Day 28(day 28)
- Lactate Dehydrogenase (LDH) at Day 7(day 7)
- Lactate Dehydrogenase (LDH) at Day 14(day 14)
- Lactate Dehydrogenase (LDH) at Day 28(day 28)
- Ferritin at Day 7(day 7)
- Ferritin at Day 14(day 14)
- Ferritin at Day 28(day 28)
- Incidence of Acute Kidney Injury (AKI)(up to 60 days)
- Incidence of Acute Liver Damage (ALD)(up to 60 days)
- Day of Death(up to 60 days)
- Mortality at Discharge(up to 60 days)
研究者
Ahmed H Hassan, PharmD
Principal Investigator
Mansoura University Hospital