COVID-19Phase 2NCT04356690
Etoposide in Patients With COVID-19 Infection
A Phase 2 study testing Etoposide in people with COVID-19, run by Boston Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2020to 1 Jul 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Single-Center, Randomized, Open-Label, Safety and Efficacy Study of Etoposide in Patients With COVID-19 Infection
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoposideDrug
Also called Etopophos
Etoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Etoposide | Experimental | Participants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4 Receives: Drug: Etoposide |
| Cohort 1 - Control | No intervention | Standard of care therapy in participants that are on ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function
8-Point Ordinal Scale of Respiratory Function: 8 -Death; 7 -Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine ≥5 μg/kg/min OR epinephrine ≥0.1 μg/kg/min OR norepinephrine ≥0.1 μg/kg/min) 6 -Intubation and mechanical ventilation 5 -Non-invasive mechanical ventilation (NIV) or high-flow oxygen 4 -Hospitalized, requiring 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
Measured: baseline, through hospital discharge or death
Secondary outcomes (8)
Overall Survival
Number of participants that lived to day 30 or hospital discharge
Measured: 30 Days
Length of Hospitalization
Number of days participants were hospitalized after treatment
Measured: From date of enrollment until date of discharge
Duration of Ventilation After Treatment
Number of days participants were ventilated after treatment
Measured: From date of enrollment until the date of extubation
Change in Blood Ferritin Levels
Change in ferritin from treatment to day 30
Measured: baseline, to day 30 (or discharge or death)
Change in C-reactive Protein (CRP) Levels
Change in CRP levels from treatment to day 30
Measured: baseline, to day 30 (or discharge or death)
Change in D-dimer Blood Levels
Change in d-dimer from treatment to day 30
Measured: baseline, to day 30 (or discharge or death)
Change in White Blood Cell Count
Change in white blood cell count from treatment to day 30
Measured: baseline, to day 30 (or discharge or death)
Change in Platelet Count
Change in platelet count from treatment to day 30
Measured: baseline, to day 30 (or discharge or death)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start8 May 2020
- Primary completion1 Jul 2022
- Study completion1 Jul 2022
Why it stopped: Slow accrual, change in COVID prevalence, availability of effective vaccine
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Boston Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Mark Sloan, Boston Medical Center
- Investigators
- John Mark Sloan, MD, Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04356690
- Sponsor's protocol ID
- H-40102
- Status last verified
- May 2023
- First submitted
- 17 Apr 2020
- Last updated
- 15 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single-Center, Randomized, Open-Label, Safety and Efficacy Study of Etoposide in Patients With COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04356690
- Acronym / sponsor ID
- H-40102
- Conditions
- COVID-19
- Keywords
- Etoposide, hemophagocytic lymphohistiocytosis (HLH), cytokine storm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual, change in COVID prevalence, availability of effective vaccine
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Boston Medical CenterUniversity, hospital or other
- Study start
- 8 May 2020 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 22 Apr 2020 (actual)
- Results
- Posted 15 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Etoposide | Experimental | Drug: EtoposideParticipants that are on ventilation Etoposide 150 mg/m2 daily days 1 and 4 |
| Cohort 1 - Control | No intervention | –Standard of care therapy in participants that are on ventilation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed COVID-19 infection
- Evidence of cytokine storm defined as:
- Cohort 1: Intubated status as a result of COVID infection-associated respiratory illness.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtoposideAlso: EtopophosEtoposide 150 mg/m2 administered intravenously once daily on Days 1 and 4. | Drug | Cohort 1 - Etoposide |
Primary outcome
Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function
Time frame: baseline, through hospital discharge or death
8-Point Ordinal Scale of Respiratory Function: 8 -Death; 7 -Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine ≥5 μg/kg/min OR epinephrine ≥0.1 μg/kg/min OR norepinephrine ≥0.1 μg/kg/min) 6 -Intubation and mechanical ventilation 5 -Non-invasive mechanical ventilation (NIV) or high-flow oxygen 4 -Hospitalized, requiring 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
8 secondary outcomes
Overall Survival
Time frame: 30 Days
Length of Hospitalization
Time frame: From date of enrollment until date of discharge
Duration of Ventilation After Treatment
Time frame: From date of enrollment until the date of extubation
Change in Blood Ferritin Levels
Time frame: baseline, to day 30 (or discharge or death)
Change in C-reactive Protein (CRP) Levels
Time frame: baseline, to day 30 (or discharge or death)
Change in D-dimer Blood Levels
Time frame: baseline, to day 30 (or discharge or death)
Change in White Blood Cell Count
Time frame: baseline, to day 30 (or discharge or death)
Change in Platelet Count
Time frame: baseline, to day 30 (or discharge or death)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Mark Sloan, MD principal investigator
Boston Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etoposide in people with COVID-19, run by Boston Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Pulmonary Status by Two Categories on an 8 Point Ordinal Scale of Respiratory Function (time frame: baseline, through hospital discharge or death). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.