Etoposide in Patients With COVID-19 Infection

Boston Medical Center (BMC)

Status and phase

Terminated

Phase 2

Conditions

COVID-19

Treatments

Drug: Etoposide

Study type

Interventional

Funder types

Other

Identifiers

NCT04356690

H-40102

Details and patient eligibility

About

This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.

Full description

The rationale for the use of etoposide to treat the cytokine storm in COVID-19 is the high mortality associated with the hyperinflammatory response to the virus, which is similar to that seen in other secondary types of Hemophagocytic lymphohistiocytosis. Autopsy studies of Acute respiratory distress syndrome (ARDS) in COVID patients show a high number of cytolytic T cells in the lungs of such patients. Early autopsy results of COVID patients at Boston Medical Center demonstrate significant hemophagocytosis in lymph nodes and spleen. Comparable studies in the related coronavirus infection severe acute respiratory syndrome (SARS) have demonstrated hemophagocytosis, a hallmark of HLH.15 By targeting the T cells and monocytes driving the cytokine storm in patients with the more severe forms of COVID infection, we hope to alleviate the progression of lung and multi-organ dysfunction characteristic of patients who die from this illness.

Enrollment

8 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Confirmed COVID-19 infection
Evidence of cytokine storm defined as:
- Peak ferritin > 10,000 ng/mL OR
- Peak ferritin > 500 ng/mL and one or more of the following at any time during hospital admission: Lactate dehydrogenase > 500 U/L, d-dimer >1000 ng/mL, C-reactive protein > 100 mg/L, or white blood count> 15 k/microlitre

Cohort 1: Intubated status as a result of COVID infection-associated respiratory illness.

Exclusion criteria

Pregnancy or breastfeeding
History of severe hypersensitivity to etoposide products
Absolute neutrophil count (ANC) < 1000 cells/mm3
Platelet count <50,000/mm3
Bilirubin > 3.0 mg/dL
Aspartate OR alanine aminotransferase > 5.0 x upper limit of normal
Creatinine Clearance < 15 mL/min (calculated by Cockcroft Fault formula)
Requiring continuous renal replacement therapy
Requiring >1 vasopressor
Requiring extracorporeal membrane oxygenation (ECMO)
Other active, life-threatening infections
Anti-cytokine treatment (including anakinra or Interleukin 6 antibodies eg tocilizumab, sarilumab) administration within three half-lives of the medication used
Hydroxychloroquine, colchicine, azithromycin, doxycycline-if administered for COVID infection-must be discontinued for at least 24 hours prior to randomization.
Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with subject participation, or is not in the best interest of the patient to participate, in the opinion of the investigator.
Inability to consent and no legally authorized representative
Poorly controlled HIV infection (CD4 count <100 cells/mm3)