COVID-19_HLH94 clinical trial

JRCT ID: jRCT2021210012

Registered date:14/06/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: severe illness patients with COVID-19
• Date of first enrollment: 24/06/2021
• Target sample size: 10
• Study type: Interventional
• Intervention(s): Etoposide 80 mg/m2 administered intravenously once daily on Days 1. If the treating clinicians feel that the patient initially benefited from etoposide but then has evidence of relapse of cytokine storm, the patient may continue on etoposide schedule of day 8. In this protocol, a combination treatment with etoposide and prednisolone is adopted. Prednisolone administrated 20 mg once daily from Day 1 to Day 7, and 10 mg once daily from Day 8 to Day 14, either intravenously or orally.

Outcome(s)

Primary Outcome

Change in pulmonary status [ Time Frame: baseline, through study completion, an average of 35 days ]
An 8 point ordinal scale will be used to assess pulmonary status consisting of the following values;
8= Death
7= Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine >=5 microg/kg/min OR epinephrine >=0.1 microg/kg/min OR norepinephrine >=0.1 microg/kg/min)
6= Intubation and mechanical ventilation
5=Non-invasive mechanical ventilation (NIV) or high-flow oxygen
4= Oxygen by mask or nasal prongs
3=Hospitalization without oxygen supplementation
2=Discharged from hospital either to home with supplemental oxygen OR to inpatient rehabilitation/skilled nursing facility (+/- supplemental oxygen)
1= Discharged to home without supplemental oxygen

Secondary Outcome

1. Duration of ventilation [Time Frame: From date of enrollment until the date of extubation, assessed study completion, an average of 35 days ]
2. Ventilator free days [Time Frame: baseline, through study completion, an average of 35 days]
3. Improvement in arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2)
4. Length of hospitalization
5. Overall survival [ Time Frame: Days 15 and 35 ]
6. Viral load in blood.
7. Changes in laboratory data

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients who have given written consent to participate in the clinical trial from themselves or a substitute.
(2) Inpatients aged 20 years or older at the time of obtaining consent
(3) Patients who have been confirmed COVID-19 by a test based on nucleic acid amplification test such as PCR or LAMP method, or by antigen testing.
(4) Patients who meet the following a and b for respiratory status
a=Confirmed COVID-19 related pneumonia by chest radiography or chest CT scan.
b=Rapid progression of respiratory failure (24-72 hours)
(5) Patients who are requiring mechanical ventilator.
(6) Patients with any of the following laboratory data suggesting cytokine release syndrome.
Ferritin >500 ng/mL and D-dimer >1 microg/mL and at least one of the following; Fever >38 deg C (within 1 day before registration), Neutrophil count/lymphocyte count ratio >10, LDH >400 U/L , CRP >15 mg/dL

Exclude criteria

(1) Pregnancy or breastfeeding
(2) History of severe hypersensitivity or adverse reactions to etoposide or prednisolone
(3) Absolute neutrophil count <1,000/microL
(4) Hemoglobin <8.0 g/dL
(5) Platelet count <50,000/microL
(6) Total bilirubin level >3.0 mg/dL
(7) Aspartate OR alanine aminotransferase > 5.0 x upper limit of normal
(8) Creatinine Clearance < 15 mL/min (calculated by Cockcroft Fault formula)
(9) Requiring continuous renal replacement therapy (CRRT)
(10) Requiring extracorporeal membrane oxygenation (ECMO)
(11) Other active, fatal infectious diseases
(12) Receiving anti-cytokine therapy (use of IL-6 inhibitors, IL-1 receptor antagonists, JAK inhibitors, etc.)
(13) Malignancy treated with chemotherapy
(14) History of HIV infection
(15) Receiving immunosuppressive drugs for autoimmune diseases or after transplantation
(16) Active hepatitis B
(17) Patients who are judged by the investigator or sub-investigator to be unlikely to survive for more than 48 hours
(18) Participating in other clinical trials or clinical research with intervention
(19) Patients who are judged by the investigator or sub-investigator to be inappropriate for this study due to medical conditions or safety reasons.

Related Information

• Primary Sponsor: Tetsuji Aoyagi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)