Covid19
Conditions
Brief summary
unicenter, randomized, open-label clinical trial on the efficacy of tocilizumab in modifying the inflammatory parameters of patients with COVID-19.
Detailed description
National, unicenter, randomized, open-label, controlled phase II clinical trial with a drug marketed and administered under conditions of use other than those approved. The study is designed to evaluate the effect of adding Tocilizumab to standard or standard of care for patients infected with COVID-19 and diagnosed with mild-moderate pneumonia. 78 patients are expected to be included in the study in a single center in Spain. The study includes a selection and randomization period, and a 28-day follow-up period (or until death, or premature withdrawal, whichever is earlier). Once the patients complete the study, they will continue with their usual follow-up.
Interventions
DRUGTocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
Tocilizumab 20 MG/ML Intravenous (one dose)
DRUGTocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)
Tocilizumab 20 MG/ML Intravenous ( two doses)
Sponsors
Hospital Universitario Ramon y Cajal
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients eligible to be included in the study will be randomized in a 1: 1: 1 ratio to receive: * TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment * TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment * Usual / standard care treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients over 18 years of age who have given their informed consent. This will be collected verbally and will be recorded in the medical record by the investigating doctor. 2. The patient is diagnosed with mild-moderate SARS-CoV-2 pneumonia confirmed microbiologically ≤7 days before randomization, and presents: to. Basal oxygen saturation\> 90% b. CURB-65 ≤1 c. PaO2 / FiO2≥300 or SatO2 / FiO2≥315 3. The patient is hospitalized or meets hospital admission criteria. 4. The patient is not expected to enter the ICU or die in the next 24 hours.
Exclusion criteria
1. Participants in another simultaneous clinical trial. 2. Use of other immunomodulators. 3. Coinfection with the hepatitis B virus (detectable AgSup-HBV). 4. Pregnancy (or planning to become pregnant during the course of the study), or lactation period. 5. Presence of laboratory abnormalities of grade ≥ 4.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3. | Day1 and Day3. | Average increase in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PaO2/FiO2 | Day3, Day7 and Day28 | Proportion of patients with PaO2 / FiO2 \<300 (or SatO2 / FiO2 ≤315) at some point in the evolution. |
| cause mortality to 28 days after started treatment | Day3, Day7 and Day28 | cause mortality to 28 days after started treatment |
| Length of hospital stay | Day3, Day7 and Day28 | Length of hospital stay |
| patients requiring Intensive Care Unit admission | Day3, Day7 and Day28 | Percentage of patients requiring Intensive Care Unit admission |
| evolution of inflammatory parameters IL12 | Day0, Day3 and Day7 | IL-12 levels at Day 7 |
| evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma | Day0, Day3 and Day7 | IL-10, IL-1, IL-6, IL-17 and IFN-gamma levels on days Day 0, Day1, Day 3 and Day 7 |
| evolution of inflammatory parameters Procalcitonin (PCT), | Day0, Day3 and Day7 | Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7 * 7 |
| evolution of inflammatory parameters C-reactive protein (PCR), | Day0, Day3 and Day7 | C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7 * 7 |
| evolution of inflammatory parameters D-dimer | Day0, Day3 and Day7 | D-dimer levels on days Day0, Day1, Day3 and Day 7 * 7 |
| Progression of pneumonia | Day3, Day7 and Day28 | Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28 |
| pharmacokinetics of tocilizumab Cmin | Day0, Day1 Day3 and Day7 | Cmin,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. |
| pharmacokinetics of tocilizumab Cmax | days Day0, Day1 Day3 and Day7 | Cmax,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. |
| pharmacokinetics of tocilizumab Cmedia | days Day0, Day1 Day3 and Day7 | Cmedia,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. |
| pharmacokinetics of tocilizumab Tmax | days Day0, Day1 Day3 and Day7 | Tmax,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. |
| pharmacokinetics of tocilizumab AUC | days Day0, Day1 Day3 and Day7 | AUC,on Day0, Day1, Day3 and Day7. On day 0 (D0), blood samples will be collected 12 hours after the infusion of each dose of tocilizumab in both experimental treatment groups. |
| Adverse event | days Day0, Day3, Day7 and Day28 | Serious and non-serious adverse events. |
| Adverse event to cause the treatment interruption. | days Day0, Day3, Day7 and Day28 | Adverse events to cause the treatment interruption. |
| Adverse event Abnormalities in laboratory | days Day0, Day3, Day7 and Day28 | Abnormalities in laboratory findings unrelated to COVID-19 disease. |
| evolution of inflammatory parameters and ferritin | Day0, Day3 and Day7 | ferritin levels on days Day0, Day1, Day3 and Day 7 * 7 |
Countries
Spain
Outcome results
None listed