Ignite Creation Date:
2024-05-06 @ 2:46 PM
Last Modification Date:
2024-10-26 @ 1:37 PM
Study NCT ID:
NCT04424056
Status:
UNKNOWN
Last Update Posted:
2020-06-23
First Post:
2020-06-08
Brief Title:
A Trial Using ANAKINRA TOCILIZUMAB Alone or in Association With RUXOLITINIB in Severe Stage 2b and 3 of COVID19-associated Disease
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
An Open Randomized Therapeutic Trial Using ANAKINRA TOCILIZUMAB Alone or in Association With RUXOLITINIB in Severe Stage 2b and 3 of COVID19-associated Disease
Status:
UNKNOWN
Status Verified Date:
2020-06
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INFLAMMACOV
Brief Summary:
COVID19-associated disease may have different clinical aspects classified in 3 stages Some patients initially presenting with a non-hypoxemic viral pneumonia stage 2a may evolve toward a more severe stage 2b or 3 acute respiratory distress syndrome ARDS around the 7th or 10th day of evolution with a severe biological inflammatory syndrome CRP200 mgl and some times more severe complications such as acute renal insufficiency consumptive coagulopathy or shock requiring increasing oxygen therapy ICU admission invasive mechanical ventilation and possibly leading to death This detrimental evolution is due to a host-derived cytokine storm with a great excess of circulating inflammatory cytokines In animal models of ARDS complicating coronavirus or influenza virus infection the cytokine storm has been linked to hyperactivation of the NLRP3 inflammasome NLRP3 constitutes an intracellular protein platform which is responsible for caspase1 activation and processing of interleukin IL-1beta and IL-18 IL-1b is a major proinflammatory cytokine which induces IL-6 whereas IL-18 is an inducer of interferon gamma IFNg production by Th-1 lymphocytes A blood IL-1IL-6 signature can be defined by increased neutrophilia and CRP concentrations whereas an IL-18IFNg signature is characterized by severe hyperferritinemia consumptive coagulopathy and cytopenia A majority of patients with COVID-19 infections seems to have an IL-1IL-6 signature evolving in the more severe forms toward an IL-18IFNg signature mimicking cytokine profiles observed in other inflammatory diseases such as Stills disease or hemophagocytic syndromes In Stills disease therapeutic inhibition of IL-1 or IL-6 has proven to be very efficient strategies During hemophagocytic syndromes inhibition of IFNg is effective in humans notably through blockade of its receptor signalization using the JAK kinase inhibitor ruxolitinib
Following this strategy we propose to use biological drugs currently available for inhibition of IL-1 anakinra IL-6 tocilizumab or IFNg signaling ruxolitinib in the severe forms of COVID19-associated disease Our hypothesis is that IL-1 IL-6 or JAK kinase inhibition will allow
1 to prevent stage 2b worsening and the need to be admitted in ICU by decreasing oxygen-requirement and systemic inflammation
2 to improve stage 3 and extremely severe stage 3 allowing invasive mechanical ventilation weaning improving multi-system organ dysfunction leading to a faster ICU exit
We propose an open randomized therapeutic trial 111 on 216 patients with severe stage 2b and 3 of the disease
Following this strategy we propose to use biological drugs currently available for inhibition of IL-1 anakinra IL-6 tocilizumab or IFNg signaling ruxolitinib in the severe forms of COVID19-associated disease Our hypothesis is that IL-1 IL-6 or JAK kinase inhibition will allow
1 to prevent stage 2b worsening and the need to be admitted in ICU by decreasing oxygen-requirement and systemic inflammation
2 to improve stage 3 and extremely severe stage 3 allowing invasive mechanical ventilation weaning improving multi-system organ dysfunction leading to a faster ICU exit
We propose an open randomized therapeutic trial 111 on 216 patients with severe stage 2b and 3 of the disease
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None