Back to resultsEfficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19 (COVITOZ-01) (COVITOZ-01)
Primary Purpose
Covid19
Status
Terminated
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- 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.
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
- The patient is hospitalized or meets hospital admission criteria.
- The patient is not expected to enter the ICU or die in the next 24 hours.
Exclusion Criteria:
- Participants in another simultaneous clinical trial.
- Use of other immunomodulators.
- Coinfection with the hepatitis B virus (detectable AgSup-HBV).
- Pregnancy (or planning to become pregnant during the course of the study), or lactation period.
- Presence of laboratory abnormalities of grade ≥ 4.
Sites / Locations
- Hospital Universitario Ramón y Cajal
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
TCZ 8 mg / kg one dose
TCZ 8 mg / kg in two
standard care treatment
Arm Description
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
Outcomes
Primary Outcome Measures
Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3.
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 Outcome Measures
Progression of pneumonia
Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28
PaO2/FiO2
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
cause mortality to 28 days after started treatment
Length of hospital stay
Length of hospital stay
patients requiring Intensive Care Unit admission
Percentage of patients requiring Intensive Care Unit admission
evolution of inflammatory parameters IL12
IL-12 levels at Day 7
evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma
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),
Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7
7
evolution of inflammatory parameters C-reactive protein (PCR),
C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7
7
evolution of inflammatory parameters D-dimer
D-dimer levels on days Day0, Day1, Day3 and Day 7
7
evolution of inflammatory parameters and ferritin
ferritin levels on days Day0, Day1, Day3 and Day 7
7
pharmacokinetics of tocilizumab Cmin
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
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
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
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
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
Serious and non-serious adverse events.
Adverse event to cause the treatment interruption.
Adverse events to cause the treatment interruption.
Adverse event Abnormalities in laboratory
Abnormalities in laboratory findings unrelated to COVID-19 disease.
Full Information
NCT ID
NCT04435717
First Posted
June 11, 2020
Last Updated
August 24, 2021
Sponsor
Hospital Universitario Ramon y Cajal
1. Study Identification
Unique Protocol Identification Number
NCT04435717
Brief Title
Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19 (COVITOZ-01)
Acronym
COVITOZ-01
Official Title
Unicenter, Randomized, Open-label Clinical Trial on the Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Futility
Study Start Date
May 4, 2020 (Actual)
Primary Completion Date
November 4, 2020 (Actual)
Study Completion Date
February 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Universitario Ramon y Cajal
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TCZ 8 mg / kg one dose
Arm Type
Experimental
Arm Description
TCZ 8 mg / kg (with a maximum of 800 mg) in single dose + usual treatment
Arm Title
TCZ 8 mg / kg in two
Arm Type
Experimental
Arm Description
TCZ 8 mg / kg in two doses at 0 and 12 hours (with a maximum of 800 mg per dose) + usual treatment
Arm Title
standard care treatment
Arm Type
No Intervention
Arm Description
Usual / standard care treatment
Intervention Type
Drug
Intervention Name(s)
Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
Intervention Description
Tocilizumab 20 MG/ML Intravenous (one dose)
Intervention Type
Drug
Intervention Name(s)
Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses)
Other Intervention Name(s)
Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1
Intervention Description
Tocilizumab 20 MG/ML Intravenous ( two doses)
Primary Outcome Measure Information:
Title
Change in IL-12 values in the 3 study groups from the start of treatment (D0) and on days D + 1 and D + 3.
Description
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.
Time Frame
Day1 and Day3.
Secondary Outcome Measure Information:
Title
Progression of pneumonia
Description
Percentage of patients per group with progression of pneumonia in Day3, Day 7 and Day28
Time Frame
Day3, Day7 and Day28
Title
PaO2/FiO2
Description
Proportion of patients with PaO2 / FiO2 <300 (or SatO2 / FiO2 ≤315) at some point in the evolution.
Time Frame
Day3, Day7 and Day28
Title
cause mortality to 28 days after started treatment
Description
cause mortality to 28 days after started treatment
Time Frame
Day3, Day7 and Day28
Title
Length of hospital stay
Description
Length of hospital stay
Time Frame
Day3, Day7 and Day28
Title
patients requiring Intensive Care Unit admission
Description
Percentage of patients requiring Intensive Care Unit admission
Time Frame
Day3, Day7 and Day28
Title
evolution of inflammatory parameters IL12
Description
IL-12 levels at Day 7
Time Frame
Day0, Day3 and Day7
Title
evolution of inflammatory parameters IL-10, IL-1, IL-6, IL-17 and IFN-gamma
Description
IL-10, IL-1, IL-6, IL-17 and IFN-gamma levels on days Day 0, Day1, Day 3 and Day 7
Time Frame
Day0, Day3 and Day7
Title
evolution of inflammatory parameters Procalcitonin (PCT),
Description
Procalcitonin (PCT), levels on days Day0, Day1, Day3 and Day 7
7
Time Frame
Day0, Day3 and Day7
Title
evolution of inflammatory parameters C-reactive protein (PCR),
Description
C-reactive protein (PCR),levels on days Day0, Day1, Day3 and Day 7
7
Time Frame
Day0, Day3 and Day7
Title
evolution of inflammatory parameters D-dimer
Description
D-dimer levels on days Day0, Day1, Day3 and Day 7
7
Time Frame
Day0, Day3 and Day7
Title
evolution of inflammatory parameters and ferritin
Description
ferritin levels on days Day0, Day1, Day3 and Day 7
7
Time Frame
Day0, Day3 and Day7
Title
pharmacokinetics of tocilizumab Cmin
Description
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.
Time Frame
Day0, Day1 Day3 and Day7
Title
pharmacokinetics of tocilizumab Cmax
Description
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.
Time Frame
days Day0, Day1 Day3 and Day7
Title
pharmacokinetics of tocilizumab Cmedia
Description
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.
Time Frame
days Day0, Day1 Day3 and Day7
Title
pharmacokinetics of tocilizumab Tmax
Description
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.
Time Frame
days Day0, Day1 Day3 and Day7
Title
pharmacokinetics of tocilizumab AUC
Description
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.
Time Frame
days Day0, Day1 Day3 and Day7
Title
Adverse event
Description
Serious and non-serious adverse events.
Time Frame
days Day0, Day3, Day7 and Day28
Title
Adverse event to cause the treatment interruption.
Description
Adverse events to cause the treatment interruption.
Time Frame
days Day0, Day3, Day7 and Day28
Title
Adverse event Abnormalities in laboratory
Description
Abnormalities in laboratory findings unrelated to COVID-19 disease.
Time Frame
days Day0, Day3, Day7 and Day28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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
The patient is hospitalized or meets hospital admission criteria.
The patient is not expected to enter the ICU or die in the next 24 hours.
Exclusion Criteria:
Participants in another simultaneous clinical trial.
Use of other immunomodulators.
Coinfection with the hepatitis B virus (detectable AgSup-HBV).
Pregnancy (or planning to become pregnant during the course of the study), or lactation period.
Presence of laboratory abnormalities of grade ≥ 4.
Facility Information:
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Tocilizumab in Modifying the Inflammatory Parameters of Patients With COVID-19 (COVITOZ-01)
We'll reach out to this number within 24 hrs