Severe COVID-19 infection with risk of need for mechanical ventilation. MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 23.0 Level: LLT Classification code 10084382 Term: Coronavirus disease 2019 System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Jakavi tablets
Product Name: Jakavi Tablets
Pharmaceutical Form: Tablet
Sponsors
Guy’s and St Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients admitted to Guy’s and St. Thomas’ NHS Foundation Trust with swab proven COVID-19 2. Deemed eligible at the time of admission for escalation to mechanical ventilation if required. 3. Worsening clinical and laboratory features suggestive of COVID-19 disease progression: ‘Yellow or Amber Category’ as judged on the current GSTT action card 21: Adult Escalation Plan for Patients with Confirmed or Suspected Covid-19 despite optimisation (example in Figure 2) –and have respiratory rate >/= 20 at any time in 24 hours prior to recruitment. - and At least two of either: CRP: >100 or Serum ferritin levels >1000ng/mL or D-dimer raised >1 µg/mL 4. Greater than 18 years of age and ability to grant full consent for repurposed use of ruxolitinib 5. No excluded concomitant medication 6. Written informed consent to participate in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 59 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 59
Exclusion criteria
Exclusion criteria: 1. Those patients below age 18 years of age 2. Not proven to have COVID-19 disease 3. Inability to grant informed consent 4. Not meeting the inclusion criteria for both clinical and biochemical features as above. 5. Pregnant or lactating and breast-feeding women 6. Unwilling to use contraception as detailed in section 5.3 7. Neutrophil counts 5 x ULN 9. Inadequate renal function as defined by GFR < 30 mls/min 10. Patients already taking JAK inhibitor therapy 11. Patients currently enrolled in another study of an investigational medicinal product. Of note, treatment with the antiviral agent remdesivir is permitted. 12. Any known contraindication or hypersensitivity to JAK inhibitor therapy (or any of the IMP excipients) such as untreated active hepatitis B or HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of this trial is to investigate the efficacy of the JAK1/2 inhibitor ruxolitinib in preventing deterioration to the point of requiring mechanical ventilation in COVID19 patients admitted to hospital.;Secondary Objective: To evaluate time to progression free survival and clinical/ laboratory responses to the intervention.;Primary end point(s): Number requiring mechanical ventilation or death in patients with COVID-19 disease [Time Frame: 28 days];Timepoint(s) of evaluation of this end point: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To evaluate time to progression free survival and clinical/ laboratory responses to the intervention 2.Clinical responses to Ruxolitinib Therapy [Time Frame: 28 days] Number of patients requiring admission to critical care unit Number of patients requiring non-invasive mechanical ventilation Time to independence from mechanical ventilation Time to independence from non-invasive mechanical ventilation Length of stay in critical care if admitted Time to independence from oxygen therapy and maintaining saturations >94% on room air. Number of patients requiring vasopressors Number of patients requiring renal replacement therapy Proportion of patients with radiological response at 7 days compared to baseline (Chest radiograph or CT scan) if available (recognising fit patients will be discharged) [Time frame 7 days] Biochemical/ laboratory response to Ruxolitinib Therapy [Time Frame 2 weeks] if available (recognising fit patients will be discharged) Partial response is at least a 25% improvement in two or more markers of CRP/Ferritin/D-dimers Time to Discharge Readmission rate 3. Assessment of Treatment related Adverse Events of Grade 3 and above as per Common Terminology Criteria for Adverse Events (CTCAE) that are not listed in the SmPC [Time frame 28 days] ;Timepoint(s) of evaluation of this end point: 28 days with the exception of Proportion of patients with radiological response at 7 days compared to baseline and Biochemical/ laboratory response to Ruxolitinib Therapy (2 weeks) | — |
Countries
United Kingdom
Contacts
Public ContactDonal McLornan
Guy’s and St Thomas' NHS Foundation Trust
Outcome results
None listed