Corona Virus Infection, SARS-CoV-2 Infection, SARS-CoV-2 PCR Test Positive, SARS-CoV-2 Acute Respiratory Disease
Conditions
Keywords
SARS-CoV-2, Covid-19, camostat mesilate, reconvalescent plasma, TMPRSS2
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALConvalescent plasma
transfusion of convalescent plasma (CP) with neutralizing antibodies against anti-SARS-CoV-2 ((titer of at least 1:160)
Tablets over 7 days, daily dose of 600 mg split into 3 doses
DRUGPlacebo for Camostat Mesilate
Placebo Tablets over 7 days, split into 3 doses
OTHERStandard of Care (SoC)
Control Arm for convalescent plasma (CP)
Sponsors
The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG)
Heinrich-Heine University, Duesseldorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The camostat mesylate and its placebo group will be double blinded while the CP and its placebo will be open label.
Intervention model description
The study is a multicenter trial that will be conducted in approx. 10 - 15 centers in Germany. At each center, patients will be randomized into four groups: two treatment groups and two control groups. The randomization rate in this study is two to one (2:1) in favor to therapy, i.e. included patients have twice the chance to receive interventional therapy than placebo / SoC.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Individuals (female, male, diverse) ≥ 18 years with SARS-CoV-2 infection, confirmed by PCR before study enrollment 2. SARS-CoV-2 positive PCR ≤ 3 days old (date of NP swab) 3. 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. 4. Ability to provide written informed consent 5. 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
Exclusion criteria
1. Age \<18 years 2. Unable to give informed consent 3. Pregnant women or breast-feeding mothers 4. Previous transfusion reaction or other contraindication to a plasma transfusion 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis 6. Volume stress due to CP administration would be intolerable 7. Known IgA deficiency 8. Life expectancy \< 6 months 9. Duration SARS-CoV-2 typical symptoms \> 3 days 10. SARS-CoV-2 PCR detection older than 3 days 11. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WHO ordinal Covid-19 scale up to day 28 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative number WHO categories 3-4a | day 8, day 14, day 28, day 56 and day 90 | Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 3-4a |
| Not hospitalized | at day 90 | Cumulative number of participants not hospitalized at day 90 |
| All-cause mortality | at day 90 | All-cause mortality at day 90 |
| Reinfection | up to day 90 | Number of patient with SARS-CoV-2 reinfection up to day 90 |
| Secondary sclerosing cholangitis (SSC) | at day 90 | Number of patient with secondary sclerosis cholangitis at day 90 |
| chronic pulmonary disease as sequelae from COVID-19 | at day 90 | Number of patient with COVID-19 associated chronic pulmonary disease |
| patients with remdesivir treatment | up to day 90 | The proportion of patients with remdesivir therapy |
| COVID-19 WHO status of patients at start of remdesivir treatment | up to day 90 | The clinical status on the WHO COVID-19 ordinal scale of at the start of remdesivir treatment WHO ordinal scale ranges from 0 to 8; whereas 0 = no COVID-19 infection and 8 = death |
| patients with dexamethasone treatment | up to day 90 | The proportion of patients on dexamethasone therapy |
| COVID-19 WHO status of patients at start of dexamethasone treatment | up to day 90 | The clinical status on the WHO COVID-19 ordinal scale of at the start of dexamethasone treatment WHO ordinal scale ranges from 0 to 8; whereas 0 = no COVID-19 infection and 8 = death |
| resolution of COVID-19 symptoms | until day of resolution up to day 90 | Time to resolution of COVID-19 related symptoms (e.g. fever) |
| negative SARS-CoV-2-PCR test | until day of first negative test up to day 90 | Time to first negative SARS-CoV-2-PCR (polymerase chain reaction) |
| Cumulative number WHO categories 4b-8 | day 8, day 14, day 56 and day 90 | Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 4b-8 |
| COVID-19 pneumonia | up to day 90 | Frequency of occurrence of COVID-19 pneumonia |
| Percentage of participants requiring mechanical ventilation | up to day 90 | Percentage of participants in each group with need for mechanical ventilation |
| Number of ventilation days per participant up to day 90 | up to day 90 | Number of ventilation days per participant up to day 90 |
| hospital stay and intensive care | up to day 90 | Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days) |
| Mortality | at day 28 | All-cause mortality at day 28 |
| SAEs | up to day 90 | Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up |
| Grade 3/4 AEs | up to day 90 | Cumulative incidence of grade 3/4 Adverse Events (AE) per group |
| SARS-CoV-2 antibody IgA concentrations | on day 8, day 14, day 90 | SARS-CoV-2 antibody concentrations (IgA in g/l) in serum on day 8, day 14, day 90 |
| SARS-CoV-2 antibody IgG concentrations | on day 8, day 14, day 90 | SARS-CoV-2 antibody concentrations (IgG in g/l) in serum on day 8, day 14, day 90 |
| SARS-CoV-2 neutralizing antibody titers | on day 8, day 14, day 90 | SARS-CoV-2 neutralizing antibody titers in serum on day 8, day 14, day 90 |
| Plasma treatment screening failures | up to day 8 (End of treatment) | Number of screening failures due to the lack of a suitable plasma preparation |
| Oxygen therapy | number of days with oxygen therapy up to day 90 | Duration of oxygen therapy (in days) |
Countries
Germany
Outcome results
None listed