Reconvalescent Plasma / Camostat Mesylate Early in Sars-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 6
- 主要终点
- WHO ordinal Covid-19 scale up to day 28
研究概览
简要总结
This study is a 4-arm, multicenter, randomized, partly double- blind, controlled trial to evaluate the safety and efficacy of convalescent serum (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 and high risk for moderate/severe COVID-19. The working hypothesis to be tested in the RES-Q-HR study is that the early use of convalescent plasma (CP) or camostat mesylate (Foipan®) reduces the likelihood of disease progression to modified WHO stages 4b-8 in SARS-CoV-2 positive adult patients at high risk of moderate or severe COVID-19 progression. The primary endpoint of the study is the cumulative number of individuals who progressed to or beyond category 4b on the modified WHO (World Health Organization) COVID-19 ordinal scale within 28 days after randomization.
详细描述
The novel coronavirus designated SARS CoV-2, and the disease caused by this virus designated COVID-19. No treatment is available for early disease stages and non-hospitalized patients to date. This trial focusses on SARS-CoV-2 positive patients with pre-existing risk factors for a moderate or severe COVID-19 disease course. This study is a 4-arm, multicenter, randomized, partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent serum (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 and high risk for moderate/severe COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. Convalescent plasma (CP) represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q HR study is that the early use of convalescent plasma (CP) or camostat mesylate (Foipan®) reduces the likelihood of disease progression to modified WHO stages 4b-8 in SARS-CoV-2 positive adult patients at high risk of moderate or severe COVID-19 progression.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The camostat mesylate and its placebo group will be double blinded while the CP and its placebo will be open label.
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
- •Individuals (female, male, diverse) ≥ 18 years with SARS-CoV-2 infection, confirmed by PCR before study enrollment
- •SARS-CoV-2 positive PCR ≤ 3 days old (date of NP swab)
- •Presence of ≥ 1 SARS-CoV-2 typical symptom (fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration <= 3 days.
- •Ability to provide written informed consent
- •Presence of at least one of the following criteria:
- •Patients > 75 years
- •Patients > 65 years with at least one other risk factor (BMI >35 kg/m2, coronary artery disease, chronic kidney disease (CKD) with glomerular filtration rate (GFR) <60 ml/min but >= 30 ml/min, diabetes mellitus, active tumor disease)
- •Patients with a BMI >35 kg/m2 with at least one other risk factor (CAD, CKD with GFR <60 ml/min but >= 30 ml/min, diabetes mellitus, active tumor disease)
- •Patients with a BMI >40 kg/m2
- •Patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis
排除标准
- •Age <18 years
- •Unable to give informed consent
- •Pregnant women or breast-feeding mothers
- •Previous transfusion reaction or other contraindication to a plasma transfusion
- •Known hypersensitivity to camostat mesylate and/or severe pancreatitis
- •Volume stress due to CP administration would be intolerable
- •Known IgA deficiency
- •Life expectancy < 6 months
- •Duration SARS-CoV-2 typical symptoms > 3 days
- •SARS-CoV-2 PCR detection older than 3 days
- •SARS-CoV-2 associated clinical condition >= WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria).
- •Previously or currently hospitalized due to SARS-CoV-2
- •Previous antiviral therapy for SARS-CoV-2
- •alanine aminotransferase (ALT) or aspartate transferase (AST) > 5 times upper limit of normal (ULN) at screening
- •Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial)
- •Chronic kidney disease with GFR < 30 ml/min
- •Concurrent or planned anticancer treatment during trial period
- •Accommodation in an institution due to legal orders (§40(4) AMG).
- •Any psycho-social condition hampering compliance with the study protocol.
- •Evidence of current drug or alcohol abuse.
- •Use of other investigational treatment within 5 half-lives of enrollment is prohibited
- •Previous use of convalescent plasma for COVID-19
- •Concomitant proven influenza A infection
- •Patients with organ or bone marrow transplant in the three months prior to Screening Visit
研究组 & 干预措施
convalescent plasma (CP)
Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1
干预措施: Convalescent plasma (Biological)
Standard of Care
Standard of care allowed
干预措施: Standard of Care (SoC) (Other)
Camostat Mesilate
Tablets 600 mg per day in 3 doses over 7 days
干预措施: Camostat Mesilate (Drug)
Placebo camostat
Placebo Tablets in 3 doses over 7 days (blinded)
干预措施: Placebo for Camostat Mesilate (Drug)
结局指标
主要结局
WHO ordinal Covid-19 scale up to day 28
时间窗: up to and including day 28
The primary endpoint of the study is the number of individuals whose clinical status is on the COVID-19 modified WHO ordinal scale ≥ 4b up to and including day 28
次要结局
- Cumulative number WHO categories 4b-8(day 8, day 14, day 56 and day 90)
- Oxygen therapy(number of days with oxygen therapy up to day 90)
- Cumulative number WHO categories 3-4a(day 8, day 14, day 28, day 56 and day 90)
- Reinfection(up to day 90)
- patients with dexamethasone treatment(up to day 90)
- negative SARS-CoV-2-PCR test(until day of first negative test up to day 90)
- Not hospitalized(at day 90)
- All-cause mortality(at day 90)
- SAEs(up to day 90)
- chronic pulmonary disease as sequelae from COVID-19(at day 90)
- COVID-19 WHO status of patients at start of dexamethasone treatment(up to day 90)
- Number of ventilation days per participant up to day 90(up to day 90)
- Secondary sclerosing cholangitis (SSC)(at day 90)
- patients with remdesivir treatment(up to day 90)
- resolution of COVID-19 symptoms(until day of resolution up to day 90)
- COVID-19 pneumonia(up to day 90)
- hospital stay and intensive care(up to day 90)
- SARS-CoV-2 antibody IgG concentrations(on day 8, day 14, day 90)
- COVID-19 WHO status of patients at start of remdesivir treatment(up to day 90)
- Mortality(at day 28)
- Grade 3/4 AEs(up to day 90)
- Percentage of participants requiring mechanical ventilation(up to day 90)
- SARS-CoV-2 antibody IgA concentrations(on day 8, day 14, day 90)
- SARS-CoV-2 neutralizing antibody titers(on day 8, day 14, day 90)
- Plasma treatment screening failures(up to day 8 (End of treatment))