Back to resultsReconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals (RES-Q-HR)
Primary Purpose
Corona Virus Infection, SARS-CoV-2 Infection, SARS-CoV-2 PCR Test Positive
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Convalescent plasma
Camostat Mesilate
Placebo for Camostat Mesilate
Standard of Care (SoC)
Sponsored by
About this trial
This is an interventional treatment trial for Corona Virus Infection focused on measuring SARS-CoV-2, Covid-19, camostat mesilate, reconvalescent plasma, TMPRSS2
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg
- Klinik und Poliklinik für Innere Medizin II Klinikum rechts der Isar Technische Universität München
- Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV
- Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie
- Klinikum Dortmund
- Universitätsklinikum Essen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Other
Experimental
Placebo Comparator
Arm Label
convalescent plasma (CP)
Standard of Care
Camostat Mesilate
Placebo camostat
Arm Description
Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1
Standard of care allowed
Tablets 600 mg per day in 3 doses over 7 days
Placebo Tablets in 3 doses over 7 days (blinded)
Outcomes
Primary Outcome Measures
WHO ordinal Covid-19 scale up to 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 Outcome Measures
Cumulative number WHO categories 4b-8
Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 4b-8
Cumulative number WHO categories 3-4a
Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 3-4a
Not hospitalized
Cumulative number of participants not hospitalized at day 90
All-cause mortality
All-cause mortality at day 90
Reinfection
Number of patient with SARS-CoV-2 reinfection up to day 90
Secondary sclerosing cholangitis (SSC)
Number of patient with secondary sclerosis cholangitis at day 90
chronic pulmonary disease as sequelae from COVID-19
Number of patient with COVID-19 associated chronic pulmonary disease
patients with remdesivir treatment
The proportion of patients with remdesivir therapy
COVID-19 WHO status of patients at start of remdesivir treatment
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
The proportion of patients on dexamethasone therapy
COVID-19 WHO status of patients at start of dexamethasone treatment
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
Time to resolution of COVID-19 related symptoms (e.g. fever)
negative SARS-CoV-2-PCR test
Time to first negative SARS-CoV-2-PCR (polymerase chain reaction)
Oxygen therapy
Duration of oxygen therapy (in days)
COVID-19 pneumonia
Frequency of occurrence of COVID-19 pneumonia
Percentage of participants requiring mechanical ventilation
Percentage of participants in each group with need for mechanical ventilation
Number of ventilation days per participant up to day 90
Number of ventilation days per participant up to day 90
hospital stay and intensive care
Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days)
Mortality
All-cause mortality at day 28
SAEs
Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up
Grade 3/4 AEs
Cumulative incidence of grade 3/4 Adverse Events (AE) per group
SARS-CoV-2 antibody IgA concentrations
SARS-CoV-2 antibody concentrations (IgA in g/l) in serum on day 8, day 14, day 90
SARS-CoV-2 antibody IgG concentrations
SARS-CoV-2 antibody concentrations (IgG in g/l) in serum on day 8, day 14, day 90
SARS-CoV-2 neutralizing antibody titers
SARS-CoV-2 neutralizing antibody titers in serum on day 8, day 14, day 90
Plasma treatment screening failures
Number of screening failures due to the lack of a suitable plasma preparation
Full Information
NCT ID
NCT04681430
First Posted
December 17, 2020
Last Updated
February 9, 2022
Sponsor
Heinrich-Heine University, Duesseldorf
Collaborators
The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG)
1. Study Identification
Unique Protocol Identification Number
NCT04681430
Brief Title
Reconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
Acronym
RES-Q-HR
Official Title
Reconvalescent Plasma / Camostat Mesylate Early in Sars-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
January 8, 2021 (Actual)
Primary Completion Date
October 29, 2021 (Actual)
Study Completion Date
October 29, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heinrich-Heine University, Duesseldorf
Collaborators
The Federal Ministry of Health, Germany (Bundesministerium für Gesundheit, BMG)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, SARS-CoV-2 Infection, SARS-CoV-2 PCR Test Positive, SARS-CoV-2 Acute Respiratory Disease
Keywords
SARS-CoV-2, Covid-19, camostat mesilate, reconvalescent plasma, TMPRSS2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The camostat mesylate and its placebo group will be double blinded while the CP and its placebo will be open label.
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
convalescent plasma (CP)
Arm Type
Experimental
Arm Description
Administration of 2 units of CP (neutralizing anti-SARS-CoV-2 antibody titer of at least 1:160) on day 1
Arm Title
Standard of Care
Arm Type
Other
Arm Description
Standard of care allowed
Arm Title
Camostat Mesilate
Arm Type
Experimental
Arm Description
Tablets 600 mg per day in 3 doses over 7 days
Arm Title
Placebo camostat
Arm Type
Placebo Comparator
Arm Description
Placebo Tablets in 3 doses over 7 days (blinded)
Intervention Type
Biological
Intervention Name(s)
Convalescent plasma
Intervention Description
transfusion of convalescent plasma (CP) with neutralizing antibodies against anti-SARS-CoV-2 ((titer of at least 1:160)
Intervention Type
Drug
Intervention Name(s)
Camostat Mesilate
Intervention Description
Tablets over 7 days, daily dose of 600 mg split into 3 doses
Intervention Type
Drug
Intervention Name(s)
Placebo for Camostat Mesilate
Intervention Description
Placebo Tablets over 7 days, split into 3 doses
Intervention Type
Other
Intervention Name(s)
Standard of Care (SoC)
Intervention Description
Control Arm for convalescent plasma (CP)
Primary Outcome Measure Information:
Title
WHO ordinal Covid-19 scale up to day 28
Description
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
Time Frame
up to and including day 28
Secondary Outcome Measure Information:
Title
Cumulative number WHO categories 4b-8
Description
Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 4b-8
Time Frame
day 8, day 14, day 56 and day 90
Title
Cumulative number WHO categories 3-4a
Description
Cumulative number of persons in the respective treatment arms versus SoC/placebo in WHO categories 3-4a
Time Frame
day 8, day 14, day 28, day 56 and day 90
Title
Not hospitalized
Description
Cumulative number of participants not hospitalized at day 90
Time Frame
at day 90
Title
All-cause mortality
Description
All-cause mortality at day 90
Time Frame
at day 90
Title
Reinfection
Description
Number of patient with SARS-CoV-2 reinfection up to day 90
Time Frame
up to day 90
Title
Secondary sclerosing cholangitis (SSC)
Description
Number of patient with secondary sclerosis cholangitis at day 90
Time Frame
at day 90
Title
chronic pulmonary disease as sequelae from COVID-19
Description
Number of patient with COVID-19 associated chronic pulmonary disease
Time Frame
at day 90
Title
patients with remdesivir treatment
Description
The proportion of patients with remdesivir therapy
Time Frame
up to day 90
Title
COVID-19 WHO status of patients at start of remdesivir treatment
Description
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
Time Frame
up to day 90
Title
patients with dexamethasone treatment
Description
The proportion of patients on dexamethasone therapy
Time Frame
up to day 90
Title
COVID-19 WHO status of patients at start of dexamethasone treatment
Description
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
Time Frame
up to day 90
Title
resolution of COVID-19 symptoms
Description
Time to resolution of COVID-19 related symptoms (e.g. fever)
Time Frame
until day of resolution up to day 90
Title
negative SARS-CoV-2-PCR test
Description
Time to first negative SARS-CoV-2-PCR (polymerase chain reaction)
Time Frame
until day of first negative test up to day 90
Title
Oxygen therapy
Description
Duration of oxygen therapy (in days)
Time Frame
number of days with oxygen therapy up to day 90
Title
COVID-19 pneumonia
Description
Frequency of occurrence of COVID-19 pneumonia
Time Frame
up to day 90
Title
Percentage of participants requiring mechanical ventilation
Description
Percentage of participants in each group with need for mechanical ventilation
Time Frame
up to day 90
Title
Number of ventilation days per participant up to day 90
Description
Number of ventilation days per participant up to day 90
Time Frame
up to day 90
Title
hospital stay and intensive care
Description
Duration of hospital stay (in days), duration in intensive care/intermediate care (IMC) (in days)
Time Frame
up to day 90
Title
Mortality
Description
All-cause mortality at day 28
Time Frame
at day 28
Title
SAEs
Description
Cumulative incidence of Serious Adverse Events (SAE) per group within 90 days follow up
Time Frame
up to day 90
Title
Grade 3/4 AEs
Description
Cumulative incidence of grade 3/4 Adverse Events (AE) per group
Time Frame
up to day 90
Title
SARS-CoV-2 antibody IgA concentrations
Description
SARS-CoV-2 antibody concentrations (IgA in g/l) in serum on day 8, day 14, day 90
Time Frame
on day 8, day 14, day 90
Title
SARS-CoV-2 antibody IgG concentrations
Description
SARS-CoV-2 antibody concentrations (IgG in g/l) in serum on day 8, day 14, day 90
Time Frame
on day 8, day 14, day 90
Title
SARS-CoV-2 neutralizing antibody titers
Description
SARS-CoV-2 neutralizing antibody titers in serum on day 8, day 14, day 90
Time Frame
on day 8, day 14, day 90
Title
Plasma treatment screening failures
Description
Number of screening failures due to the lack of a suitable plasma preparation
Time Frame
up to day 8 (End of treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Verena Keitel-Anselmino, Prof.Dr.med.
Organizational Affiliation
Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abteilung Infektiologie Klinik für Innere Medizin II Department Innere Medizin Universitätsklinikum Freiburg
City
Freiburg im Breisgau
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Klinik und Poliklinik für Innere Medizin II Klinikum rechts der Isar Technische Universität München
City
München
State/Province
Bavaria
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitätsklinikum Frankfurt Medizinische Klinik 2: Hämatologie, Onkologie, Hämostaseologie, Rheumatologie, Infektiologie/HIV
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf Klinik für Hepatologie und Infektiologie
City
Duesseldorf
State/Province
North Rhine Westphalia
ZIP/Postal Code
40225
Country
Germany
Facility Name
Klinikum Dortmund
City
Dortmund
State/Province
North Rhine-Westphalia
ZIP/Postal Code
44137
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
45147
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34001215
Citation
Keitel V, Jensen B, Feldt T, Fischer JC, Bode JG, Matuschek C, Bolke E, Budach W, Plettenberg C, Scheckenbach K, Kindgen-Milles D, Timm J, Muller L, Kolbe H, Stohr A, Calles C, Hippe A, Verde P, Spinner CD, Schneider J, Wolf T, Kern WV, Nattermann J, Zoufaly A, Ohmann C, Luedde T; RES-Q-HR Trial Team. Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial. Trials. 2021 May 17;22(1):343. doi: 10.1186/s13063-021-05181-0.
Results Reference
derived
Learn more about this trial
Reconvalescent Plasma/Camostat Mesylate Early in SARS-CoV-2 Q-PCR (COVID-19) Positive High-risk Individuals
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