Covid19
Conditions
Brief summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Camostat mesylate, compared to placebo in adult patients with ambulatory COVID-19 disease, presenting with risk factors of severe COVID-19. Camostat mesylate is a serine protease TMPRSS2 (Transmembrane Serine Protease 2) inhibitor which has been successfully and safely used to treat pancreatitis-associated pain and post-operative reflux oesophagitis in Japan. More recently, it has been shown to inhibit SARS-CoV-2 viral entry and reduce infection of human primary pneumocytes and lung cell lines. Camostat mesylate or placebo will be administered to consenting adult patients with virologically confirmed COVID-19, not requiring initial hospitalization. All patients will receive standard of care along with randomized treatments. Outcomes of included patients will be compared between the 2 groups.
Interventions
Camostat mesylate, oral administration 600mg/day (2 x 100mg tablets every 8 hours) for 14 days
DRUGPlacebo
Placebo tablets, oral administration 2 tablets every 8 hours for 14 days
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years old * Patients with an increased risk of severe COVID-19 belonging to one or more of the following groups : * Age ≥ 50 years * Body Mass Index ≥ 30 kg/m² * Diabetes * Hypertension * Chronic renal failure (eGFR \<60 mL/min) * Chronic heart disease * Asthma/Chronic Obstructive Pumonary Disease/Cystic fibrosis * Chronic liver disease * Chronic neurological disease * Solid organ transplant * Bone marrow transplant * Sickle cell anemia/ Major thalassemias * Active or currently treated or \<1 year diagnosed cancer * Active or currently treated or \<1 year diagnosed malignant blood disease * Immunosuppressive treatment observed for more than 1 month * Laboratory confirmed SARS-CoV2 infection with mild COVID-19, fulfilling all the following criteria: * Positive SARS-CoV-2 RT-PCR nasal swab samples AND * Clinical symptoms and signs consistent with SARS-CoV2 infection including but not limited to, fever, upper respiratory tract infection signs, digestive signs, muscle pain, anosmia, dysgueusia…(1) * Informed consent to participate to the trial * Patients must be able and willing to comply with study visits and procedures
Exclusion criteria
* Initial need for hospitalization for COVID-19 management * Pregnancy and breastfeeding * Participation to another interventional drug trial * Subject protected by law under guardianship or curatorship * Absence of health insurance * Known hypersensitivity to camostat mesylate * Known person sharing the same household already included in the study * Participation to another COVID-19 ambulatory interventional study * Patients having completed a full SARS-CoV2 vaccine immunization procedure less than 4 weeks prior to COVID-19 diagnosis (last vaccine injection performed less than 4 weeks prior to COVID-19 diagnosis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization for COVID-19 deterioration or death without hospitalization | Day 21 | Proportion of patients hospitalized for COVID-19 deterioration or who died without hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Day 21 | Number of patients with at least one adverse event |
| Serious adverse events | Day 21 | Number of patients with at least one serious adverse event |
| Investigational medication discontinuation | Day 21 | Number of patients who discontinued the investigational medication |
| Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee | Day 21 | Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization |
| Clinical improvement using the Word Health Organization (WHO) COVID-19 scale | Day 7, 14, 21 | WHO clinical scale: Uninfected - No clinical or virological evidence of infection: 0; Ambulatory - No limitation of activities: 1; Ambulatory - limitation of activities: 2; Hospitalized - no oxygen therapy: 3; Hospitalized - oxygen by mask or nasal prongs: 4; Hospitalized; oxygen by non invasive ventilation or High flow: 5; Intubation and Mechanical ventilation: 6; Mechanical ventilation + additional organ support (pressors, Renal replacement therapy, ECMO):7; Dead: 8 |
| Need for intensive care | Day 21 | Proportion of patients admitted to an intensive care unit |
| Duration of hospitalization | Day 21 | Number of days alive without hospitalization up to day 21 |
| Need for invasive mechanical ventilation for severe COVID-19 | Day 21 | Proportion of patients with initiation of invasive mechanical ventilation |
| Need for oxygen therapy for COVID-19 | Day 21 | Proportion of patients with initiation of oxygen therapy |
| Overall survival | Day 90 | Proportion of patients alive at day 90 |
| SARS-CoV-2 virological assessment | Day 7, 14, 21 | By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia) |
| SARS-CoV-2 serological assessment | Day 7, 14, 21 and 90 | SARS-CoV2 antibodies quantification in blood |
| Peripheral blood lymphocyte phenotyping | Day 1, 14, 90 | Peripheral blood lymphocyte phenotyping with telomere length measurement |
| Acute kidney failure | Day 21 | Acute kidney failure defined as at least serum creatinine increase of 0.3mg/dl or 1.5-1.9 times baseline and/or oliguria \< 0.5ml/kg/h |
| Renal function | Day 7, 14 and 21 | estimated glomerular filtration rate |
| Concentration of urea in blood | Day 7, 14 and 21 | Uricemia in mmol/L or mg/dL |
| Concentration of potassium in blood | Day 7, 14 and 21 | Kaliemia in mmol/L |
| Liver function | Day 7, 14 and 21 | Liver transaminases dosage on blood sample |
| Liver function (2) | Day 7, 14 and 21 | Gamma-glutamyl transferase (gamma-GT) dosage on blood sample |
| Duration of symptoms | Day 21 | Number of days alive without symptoms at day 21 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Biobanking for biomarker assessment | Day 1, 7, 14, 21, 90 | Biobanking of blood samples for predictive biomarker assessment |
Countries
France
Outcome results
None listed