Coronavirus InfectionPhase 2TOCIDEXNCT04476979
Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19
A Phase 2 study testing Tocilizumab and Dexamethasone in people with Coronavirus Infection and SARS (Severe Acute Respiratory Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in French Guiana.
Trial summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus Infection, SARS (Severe Acute Respiratory Syndrome), Virus Diseases
- What is being tested?
- Tocilizumab and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 453 participants
- Where
- 1 siteFrench Guiana
- Study dates
- 16 Jul 2020to 11 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients included in the CORIMUNO-19 cohort
- Patients belonging to the following group:
- Requiring ≥ 3L/min of oxygen
- WHO progression scale = 5
- No NIV or High flow
Who cannot join
- Patients with exclusion criteria to the CORIMUNO-19 cohort.
- Known hypersensitivity to Tocilizumab or DXM or to any of their excipients.
- Pregnancy
- Current documented bacterial infection not controlled by antibiotics.
- certain evolving viral diseases (especially active herpes, chickenpox, shingles),
- psychotic states still not controlled by treatment,
Show all 13Show fewer
- live vaccines in the previous 4 weeks,
- Active tuberculosis or disseminated strongyloidiasis
- Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
- Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
- Haemoglobin level: no limitation
- Platelets (PLT) < 50 G /L
- SGOT or SGPT > 5N
Trial locations and contacts
1 site in 1 country.
About this study
The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19).
Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R.
Read more
The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Dexamethasone alone or Dexamethasone +Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort.
Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation.
Patients who will chose not to receive Tocilizumab will receive standard of cares.
Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care (including Dexamethasone) treated patients
- Conditions
- Coronavirus Infection, SARS (Severe Acute Respiratory Syndrome), Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections
- Being tested
- Tocilizumab, Dexamethasone
- Medical subject headings
- Coronavirus Infections, Severe Acute Respiratory Syndrome, Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Respiratory Tract Infections, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
DexamethasoneDrug
Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone | Active comparator | Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) Receives: Drug: Dexamethasone |
| Dexamethasone + Tocilizumab | Experimental | Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
+Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3 Receives: Drug: Tocilizumab; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without needs of invasive ventilation at day 14
Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation.
Measured: day 14
Secondary outcomes (6)
WHO progression scale at day 7 and 14
WHO progression scale:
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measured: day 7 and day 14
Overall survival at 14, 28, 60 and 90 days
Overall survival
Measured: 14, 28, 60 and 90 days
Cumulative incidence of discharge alive at 14 and 28 days
Cumulative incidence of discharge alive
Measured: 14 and 28 days
Survival without needs of mechanical ventilation at day 1
Survival without needs of mechanical ventilation at day 1. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measured: day 1
Cumulative incidence of oxygen supply independency at 14 and 28 days
Cumulative incidence of oxygen supply independency
Measured: 14 and 28 days
Survival without needs of ventilator utilization at day 14
Survival without needs of ventilator utilization (including non-invasive ventilation and Optiflow) at day 14
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start16 Jul 2020
- Primary completion1 Jun 2021
- Study completion11 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronavirus InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 453 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04476979
- Sponsor's protocol ID
- APHP200375-TOCIDEX
- Other IDs
- 2020-001246-18
- Acronym
- TOCIDEX
- Status last verified
- May 2024
- First submitted
- 16 Jul 2020
- Last updated
- 31 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hermine O, Mariette X, Porcher R, Djossou F, Nguyen Y, Arlet JB, Savale L, Diehl JL, Georgin-Lavialle S, Cadranel J, Pialoux G, Lacombe K, Mekinian A, Gros H, Lescure X, Ghosn J, Coupez E, Grapin K, Rapp C, Michel M, Lecapitaine AL, Michot JM, Costedoat-Chalumeau N, Nguyen LBL, Semerano L, Raffi F, Aguillar C, Rouzaud C, Gottenberg JE, Hansmann Y, Bienvenu B, London J, Fantchou FS, Ackermann F, Gros A, Morel A, Gambier N, Sene D, Megarbane B, Azoulay E, Bureau S, Dougados M, Emmerich J, Fartoukh M, Guidet B, Humbert M, Mahevas M, Pene F, Schlemmer F, Pourcher-Martinez V, Tibi A, Baron G, Perrodeau E, Baron S, Steg G, Yazdapanah Y, Simon T, Resche-Rigon M, Tharaux PL, Ravaud P. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group. EClinicalMedicine. 2022 Mar 25;46:101362. doi: 10.1016/j.eclinm.2022.101362. eCollection 2022 Apr.
PubMed 35350097
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19
- ClinicalTrials.gov ID
- NCT04476979
- Acronym / sponsor ID
- TOCIDEX / APHP200375-TOCIDEX
- Conditions
- Coronavirus Infection, SARS (Severe Acute Respiratory Syndrome), Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 453 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 16 Jul 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 11 Aug 2021 (actual)
- First posted
- 20 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19).
Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R.
The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Dexamethasone alone or Dexamethasone +Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort.
Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation.
Patients who will chose not to receive Tocilizumab will receive standard of cares.
Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care (including Dexamethasone) treated patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone | Active comparator | Drug: DexamethasoneDexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) |
| Dexamethasone + Tocilizumab | Experimental | Drug: Tocilizumab, Drug: DexamethasoneDexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) +Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients included in the CORIMUNO-19 cohort
- Patients belonging to the following group:
Key exclusion criteria (13 listed)
- Patients with exclusion criteria to the CORIMUNO-19 cohort.
- Known hypersensitivity to Tocilizumab or DXM or to any of their excipients.
- Pregnancy
- Current documented bacterial infection not controlled by antibiotics.
- certain evolving viral diseases (especially active herpes, chickenpox, shingles),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabTocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3 | Drug | Dexamethasone + Tocilizumab |
| DexamethasoneDexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner) | Drug | Dexamethasone, Dexamethasone + Tocilizumab |
Primary outcome
Survival without needs of invasive ventilation at day 14
Time frame: day 14
Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation.
6 secondary outcomes
WHO progression scale at day 7 and 14
Time frame: day 7 and day 14
Overall survival at 14, 28, 60 and 90 days
Time frame: 14, 28, 60 and 90 days
Cumulative incidence of discharge alive at 14 and 28 days
Time frame: 14 and 28 days
Survival without needs of mechanical ventilation at day 1
Time frame: day 1
Cumulative incidence of oxygen supply independency at 14 and 28 days
Time frame: 14 and 28 days
Survival without needs of ventilator utilization at day 14
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2024.
- Results publication: PubMed 35350097Hermine O, Mariette X, Porcher R, Djossou F, Nguyen Y, Arlet JB, Savale L, Diehl JL, Georgin-Lavialle S, Cadranel J, Pialoux G, Lacombe K, Mekinian A, Gros H, Lescure X, Ghosn J, Coupez E, Grapin K, Rapp C, Michel M, Lecapitaine AL, Michot JM, Costedoat-Chalumeau N, Nguyen LBL, Semerano L, Raffi F, Aguillar C, Rouzaud C, Gottenberg JE, Hansmann Y, Bienvenu B, London J, Fantchou FS, Ackermann F, Gros A, Morel A, Gambier N, Sene D, Megarbane B, Azoulay E, Bureau S, Dougados M, Emmerich J, Fartoukh M, Guidet B, Humbert M, Mahevas M, Pene F, Schlemmer F, Pourcher-Martinez V, Tibi A, Baron G, Perrodeau E, Baron S, Steg G, Yazdapanah Y, Simon T, Resche-Rigon M, Tharaux PL, Ravaud P. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group. EClinicalMedicine. 2022 Mar 25;46:101362. doi: 10.1016/j.eclinm.2022.101362. eCollection 2022 Apr.
- Individual participant dataSharing planned: Undecided
Related trials for Coronavirus Infection
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
RecruitingObservational study
Cardiovascular Disease Progression in Survivors of Community Acquired Pneumonia and Lung Infection by Covid-19.
Pneumonia, Community-Acquired, COVID-19 Pneumonia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab and Dexamethasone in people with Coronavirus Infection and SARS (Severe Acute Respiratory Syndrome), run by Assistance Publique - Hôpitaux de Paris at 1 site in French Guiana.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in French Guiana. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without needs of invasive ventilation at day 14 (time frame: day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04476979, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2024.