Etoposide in Patients With COVID-19 Infection

NCT ID: NCT04356690

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2022-07-01

Brief Summary

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.

Detailed 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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Cohort 1 - Etoposide

Participants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4.

Cohort 1 - Control

Standard of care therapy in participants that are on ventilation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Etoposide

Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4.

Intervention Type: DRUG

Other Intervention Names

Etopophos

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

John Mark Sloan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Mark Sloan, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

Boston Medical Center

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

H-40102

Identifier Type: -

Identifier Source: org_study_id