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Completed

NCT Number: NCT04409262

A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia

This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

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Key information

Conditions

COVID-19 Pneumonia

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Santa Casa de Misericordia de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Hospitalized with COVID-19 pneumonia confirmed per a positive polymerase chain reaction (PCR) of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
  • Requiring more than 6 L/min supplemental oxygen to maintain SpO2 > 93%
  • Agrees to not participate in another clinical trial for the treatment of COVID-19 while participating in this study

Exclusion criteria

  • Known severe allergic reactions to tocilizumab or other monoclonal antibodies
  • Known hypersensitivity to remdesivir, the metabolites, or formulation excipients
  • Active tuberculosis (TB) infection
  • Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
  • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
  • Treatment with immunosuppressive or immunomodulatory therapy (including tocilizumab) within the past 3 months
  • Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 within 24 hours prior to study drug dosing. In addition, participants with prior or current treatment with > 2 doses of remdesivir for COVID-19 are excluded
  • Participating in other drug clinical trials
  • Estimated glomerular filtration rate (eGFR) < 30 mL/min (including patients receiving hemodialysis or hemofiltration)
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN) detected within 24 hours of screening (according to local laboratory reference ranges)
  • Absolute neutrophil count (ANC) < 1000/uL at screening
  • Platelet count < 50,000/uL at screening
  • Body weight < 40 kg
  • Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization

Treatment and study plan

Remdesivir

Drug

Participants will receive intravenous (IV) RDV

Tocilizumab

Drug

Participants will receive IV TCZ

Placebo

Drug

Participants will receive IV placebo matched to TCZ

Primary outcomes

  1. Time to Hospital Discharge or "Ready for Discharge" up to Day 28

    Time frame: Up to Day 28

    Defined as days from randomization to hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death. Hospital discharge or "Ready for Discharge" is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28.

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

Secondary outcomes

  1. Time to Mechanical Ventilation or Death up to Day 28

    Time frame: Up to Day 28

    Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event.

  2. Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14

    Time frame: Day 14

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  3. Time to Death up to Day 28

    Time frame: Up to Day 28

    Time to death is defined as the time from randomization to death.

  4. Time to Death up to Day 60

    Time frame: Up to Day 60

    Time to death is defined as the time from randomization to death.

  5. Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28

    Time frame: Up to Day 28

    Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28.

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  6. Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7

    Time frame: Day 7

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  7. Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21

    Time frame: Day 21

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  8. Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28

    Time frame: Day 28

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  9. Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60

    Time frame: Day 60

    Clinical status was assessed by the investigator according to the following ordinal scale categories:

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  10. Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline)

    Time frame: Day 28 and Day 60

    Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event.

    Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event.

  11. Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline)

    Time frame: Day 28 and Day 60

  12. Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28

    Time frame: Up to Day 28

    Participants who die by Day 28 are assigned a duration of 28 days.

  13. Difference in Mortality at Days 14, 28, and 60

    Time frame: Days 14, 28, and 60

  14. Time to Recovery up to Day 28

    Time frame: Up to Day 28

    Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or "ready for hospital ward" not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category >2 or death. Participants who die are censored at day 28.

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  15. Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28

    Time frame: Up to Day 28

    Defined as hospital discharge or "Ready for Discharge" not followed by ordinal scale category >1, hospital readmission or death.

    • Discharged (or "ready for discharge" as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or </= 2L supplemental oxygen)
    • Non-intensive care unit (ICU) hospital ward (or "ready for hospital ward") not requiring supplemental oxygen
    • Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen
    • ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen
    • ICU, requiring intubation and mechanical ventilation
    • ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy)
    • Death

  16. Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28

    Time frame: Up to Day 28

    Participants already on mechanical ventilation at baseline are only counted as an event if death occurs.

Other outcomes

  1. Percentage of Participants With Adverse Events (AEs) Tabulated by Severity

    Time frame: Up to Day 60

    AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

    Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE

    Participants are counted at the highest AE grade experienced.

  2. Proportion of Participants With Any Post-Treatment Infection

    Time frame: Up to Day 60

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • Gilead Sciences

Registry information

Official study title

A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

Acronym: REMDACTA

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jun 1, 2020
Registry last updated
Feb 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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