ARDS, Human, COVID
Conditions
Keywords
Covid-19, ARDS, Ruxolitinib, Janus kinase, JAK1, JAK2
Brief summary
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 severe pneumonia.
Detailed description
This clinical trial is an open-label trial of ruxolitinib for the treatment of severe COVID-19 to assess its efficacy and safety. Ruxolitinib (INCB018424 phosphate, INC424, ruxolitinib phosphate) is a well established, potent and selective inhibitor of Janus kinase (JAK)1 and JAK2, with modest to marked selectivity against tyrosine kinase (TYK)2 and JAK3, respectively. Ruxolitinib interferes with the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Ruxolitinib (JAKAVI®) is currently approved in the European Union (EU) for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (PMF) (also known as chronic idiopathic MF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) and for the treatment of adult patients with PV who are resistant to or intolerant of hydroxyurea (HU). In the US, ruxolitinib has been approved in the treatment of steroid refractory graft versus host disease post allogeneic stem cell transplantation. Because many patients with severe respiratory disease due to COVID-19 have features consistent with the cytokine release syndrome (CRS) and increased activation of the JAK/STAT pathway, it is postulated that ruxolitinib might have a useful role in treating these patients.
Interventions
DRUGRuxolitinib administration
Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function.If the patient is discharged before day 28, the therapy will be discontinued for discharge.
Sponsors
Philipps University Marburg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function; open design, single arm.If the patient is discharged before day 28, the therapy will be discontinued for discharge.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant female adult ≥18 years of age at time of enrollment. 2. has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay (result of the PCR is not necessary for inclusion, but has to approved latest within 48-72 hours after registration) 3. Willingness of men and women of childbearing potential to use highly effective contraceptive methods by abstinence or by using at least two contraceptive methods from the date of consent to the end of the study 4. severe lung disease as defined by following: 1. Recent intubation 2. Requirement of invasive ventilation moderate to severe pulmonary oxygen exchange disturbance as defined by (PaO2/FiO2) ≤ 200 mmHg at a PEEP ≥ 5mm H2O 3. Serum LDH \> 283 U/l 4. Ferritin above normal value 5. CT-scan: pulmonary infiltration compatible with Covid-19 disease 5. Patient or patient´s representative must provide written informed consent (and assent if applicable) before any study assessment is performed.
Exclusion criteria
1. Uncontrolled HIV infection 2. Active tuberculosis (result of positive tuberculosis infection is not necessary for exclusion, but has to approved later on during patient´s intervention) 3. Chronic kidney disease requiring dialysis 4. ALT/AST \> 5 times the upper limit of normal. 5. Pregnancy or breast feeding. 6. Allergy to study medication 7. Simultaneous participation in another clinical trial with an experimental treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 28 days after registration into trial | To determine the efficacy of ruxolitinib measured by overall survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cytokine storm | registration until 90 days after registration into trial | Assessment of the extent of cytokine storm reduction (IL-6, CRP, ferritin) |
| time on ICU | registration until 90 days after registration into trial | To assess time on ICU |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | registration until 90 days after registration into trial | In order to classify the severity of the AEs, number of participants with treatment-related adverse events will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| time frame for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG) | registration until 90 days after registration into trial | To assess the timeframe for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG) |
| Rates of flow | Discharge from hospital (end of treatment) | To asses the rates of flow (liter/minute), in order to detect possible amelioration of pulmonary function after Covid-19 infection |
| Assessment of the duration of ventilation support | registration until 90 days after registration into trial | Assessment of the duration of ventilation support |
| Forced expiratory volume in 1 second (FEV1) | Discharge from hospital (end of treatment) | To assess forced expiratory volume in 1 second (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection |
| Forced vital capacity (FVC) | Discharge from hospital (end of treatment) | To assess forced vital capacity (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection |
| Tiffeneau-Pinelli index | Discharge from hospital (end of treatment) | To assess Tiffeneau-Pinelli index (FEV1/FVC ratio in %), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection |
| Overall survival | 90 days after registration into trial | To determine the efficacy of ruxolitinib measured by overall survival |
| Gas exchange | Discharge from hospital (end of treatment) | To asses gas exchange (partial pressure of oxygen and carbon dioxide), in order to detect possible amelioration of pulmonary function after Covid-19 infection |
Countries
Germany
Outcome results
None listed