Acute Respiratory Distress SyndromePhase 3SILVARNCT04616586
SILtuximab in Viral ARds (SILVAR) Study
A Phase 3 study testing Siltuximab and Normal Saline in people with Acute Respiratory Distress Syndrome and Lung Diseases, run by RECORDATI GROUP at 2 sites in United States.
Trial summary
This study will evaluate the efficacy and safety of siltuximab compared with normal saline in combination with standard of care (SOC) in selected hospitalized patients with COVID-19 previously treated with corticosteroids or another respiratory virus infection associated with acute respiratory distress syndrome (ARDS)… Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Lung Diseases, Pneumonia
- What is being tested?
- Siltuximab and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 555 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Nov 2020to 1 Apr 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Positive microbiological evidence of SARS-CoV-2 or another respiratory virus infection (eg, other coronaviruses, respiratory syncytial virus, influenza virus) following institutional diagnostic standards
- Clinical and radiological diagnosis of pulmonary infection requiring noninvasive or mechanical invasive ventilatory support plus administration of rising supplemental oxygen concentrations
- Treatment of SARS-CoV-2-infected patients with dexamethasone (or equivalent) administered by mouth or intravenous (IV) injection
- Diagnosis of ARDS (PaO2/FiO2 ≤200 with positive end-expiratory pressure ≥5 cmH2O) in accordance with Berlin 2012 criteria1 (measured on or after the fourth day after the start of corticosteroid therapy in those patients for whom it was prescribed)
- Serum CRP level greater than upper limit of normal (measured on or after the third day after the start of corticosteroid therapy in those patients for whom it was prescribed) on 2 consecutive days
- Age ≥12 years
Who cannot join
- Active bacterial or fungal infection, human immunodeficiency virus (HIV), HHV, Epstein-Barr virus, or other non-respiratory virus infection, or tuberculosis requiring initiation of anti-infective therapy
- Prior treatment with an agent targeting the IL-6 signaling pathway
- Current treatment in another therapeutic clinical trial (other than expanded remdesivir access protocol)
- Start of new immunosuppressive therapy (including but not limited to corticosteroids and cytokine signaling pathway inhibitors) within 4 days prior to study entry (randomization); start of new antiviral treatment (including but not limited to nucleoside analogues, aminoquinoline compounds, and convalescent plasma) within 2 days prior to randomization; or received a live vaccine at any time prior to randomization, or plan to receive a live vaccine during the study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Atrium Health
Charlotte, North Carolina, 28202
Sparrow Clinical Research Institute
Lansing, Michigan, 48912
About this study
Official title: A Study Comparing the Efficacy and Safety of Standard of Care With or Without Siltuximab in Selected Hospitalized Patients With Viral Acute Respiratory Distress Syndrome (SILVAR)
This study will evaluate the efficacy and safety of siltuximab compared with normal saline in combination with standard of care (SOC) in selected hospitalized patients with COVID-19 previously treated with corticosteroids or another respiratory virus infection associated with acute respiratory distress syndrome (ARDS) and elevated C-reactive protein (CRP) levels.
Read the detailed description
This is a prospective, multicenter, randomized (2:1), double-blind, parallel-arm, placebo-controlled, Phase 3 clinical trial of 1-3 doses of siltuximab 11 mg/kg IV over 1 hour plus SOC vs. matched-volume normal saline (NS) IV over 1 hour plus SOC in 555 patients with SARS CoV-2 previously treated with corticosteroids or another respiratory virus infection with elevated CRP levels who have developed serious respiratory complications.
The randomization will be stratified by age (<65, ≥65 years), respiratory virus infection (confirmed SARS-CoV-2, other), and MIV status (yes, no). Crossover between treatment arms will not be allowed.
All patients will receive ARDS SOC following the official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline13 and/or the World Health Organization's (WHO's) clinical management of severe acute respiratory infection when COVID-19 disease is suspected (WHO Interim Guidance 202014 or other local guidance). Patients may continue receiving their corticosteroid (up to a cumulative maximum dexamethasone or equivalent dose of 60 mg [except to treat treatment-emergent reactions or comorbid conditions]) or antiviral therapy (except aminoquinoline compounds and convalescent plasma) at the same or lower doses if started at least 4 days (corticosteroid therapy) or at least 2 days (antiviral therapy) prior to randomization. Patients randomized to Arm A will additionally receive siltuximab 11 mg/kg IV administered over 1 hour, while patients randomized to Arm B will additionally receive IV NS administered over 1 hour, with opportunity to repeat their assigned study treatment once or twice at least 2 days apart on or after Day 3 as their clinical condition and/or laboratory testing dictate.
- Conditions
- Acute Respiratory Distress Syndrome, Lung Diseases, Pneumonia, Respiratory Tract Infections, Respiratory Tract Disease
- Being tested
- Siltuximab, Normal Saline
- Keywords
- Siltuximab, ARDS
- Medical subject headings
- Respiratory Distress Syndrome, Lung Diseases, Pneumonia, Respiratory Tract Infections, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiltuximabDrug
Also called Sylvant
11 mg/kg IV administered over 1 hour
Normal SalineOther
IV administered over 1 hour
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Drug - Siltuximab Receives: Drug: Siltuximab |
| Arm B | Other | Comparator - Normal Saline Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
28-day all-cause mortality
28-day all-cause mortality
Measured: Day 28
Secondary outcomes (14)
Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)
Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)
Measured: Up to 60 days
Ventilator-free days (VFDs) within 28 days
Ventilator-free days (VFDs) within 28 days
Measured: Up to 28 days
Organ failure-free days (OFFD)
Organ failure-free days (OFFD)
Measured: Up to 60 days
Intensive care unit length of stay (ICU LOS)
Intensive care unit length of stay (ICU LOS)
Measured: Up to 60 days
Hospital length of stay (HLOS)
Hospital length of stay (HLOS)
Measured: Up to 60 days
In-hospital all-cause mortality (IHACM)
In-hospital all-cause mortality (IHACM)
Measured: Up to 60 days
60-day all-cause mortality (60DACM)
60-day all-cause mortality (60DACM)
Measured: Up to 60 days
Time to oxygenation improvement (TOI)
Time to oxygenation improvement (TOI)
Measured: Up to 60 days
Duration of supplemental oxygen (DSO)
Duration of supplemental oxygen (DSO)
Measured: Up to 60 days
Chest radiographic improvement (CRI)
Chest radiographic improvement (CRI)
Measured: Up to 60 days
Time to National Early Warning Score 2 improvement (TNEWS2I)
Time to National Early Warning Score 2 improvement (TNEWS2I)
Measured: Up to 60 days
Treatment-emergent adverse events (TEAEs)
Treatment-emergent adverse events (TEAEs)
Measured: Up to 60 days
Plasma siltuximab concentrations (PSCs)
Plasma siltuximab concentrations (PSCs)
Measured: Up to 60 days
Anti-siltuximab antibodies (ASA)
Anti-siltuximab antibodies (ASA)
Measured: Up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2020
- Study start13 Nov 2020
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
Why it stopped: The REMAP-CAP and RECOVERY substudy results appear to support the survival benefit of tocilizumab in corticosteroid-treated or untreated patients with critically ill COVID-19-associated ARDS.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, multicenter, randomized (2:1), double-blind, parallel-arm, placebo-controlled, Phase 3 clinical trial of 1-3 doses of siltuximab 11 mg/kg IV over 1 hour plus SOC vs. matched-volume normal saline (NS) IV over 1 hour plus SOC in 555 patients with SARS-CoV-2 previously treated with corticosteroids or another respiratory virus infection with elevated CRP levels who have developed serious respiratory complications
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 555 participants (actual)
Sponsor and investigators
- Lead sponsor
- RECORDATI GROUP
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
- Investigators
- Zainab Shahid, MD, Ph.D, Principal investigator, Participating Site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04616586
- Sponsor's protocol ID
- EUSA SYL 0004
- Acronym
- SILVAR
- Status last verified
- Jan 2021
- First submitted
- 10 Oct 2020
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study Comparing the Efficacy and Safety of Standard of Care With or Without Siltuximab in Selected Hospitalized Patients With Viral Acute Respiratory Distress Syndrome (SILVAR)
- ClinicalTrials.gov ID
- NCT04616586
- Acronym / sponsor ID
- SILVAR / EUSA SYL 0004
- Conditions
- Acute Respiratory Distress Syndrome, Lung Diseases, Pneumonia, Respiratory Tract Infections, Respiratory Tract Disease
- Keywords
- Siltuximab, ARDS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The REMAP-CAP and RECOVERY substudy results appear to support the survival benefit of tocilizumab in corticosteroid-treated or untreated patients with critically ill COVID-19-associated ARDS.
- Enrolment
- 555 participants (actual)
- Lead sponsor
- RECORDATI GROUPIndustry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 5 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy and safety of siltuximab compared with normal saline in combination with standard of care (SOC) in selected hospitalized patients with COVID-19 previously treated with corticosteroids or another respiratory virus infection associated with acute respiratory distress syndrome (ARDS) and elevated C-reactive protein (CRP) levels.
Detailed description
This is a prospective, multicenter, randomized (2:1), double-blind, parallel-arm, placebo-controlled, Phase 3 clinical trial of 1-3 doses of siltuximab 11 mg/kg IV over 1 hour plus SOC vs. matched-volume normal saline (NS) IV over 1 hour plus SOC in 555 patients with SARS CoV-2 previously treated with corticosteroids or another respiratory virus infection with elevated CRP levels who have developed serious respiratory complications.
The randomization will be stratified by age (<65, ≥65 years), respiratory virus infection (confirmed SARS-CoV-2, other), and MIV status (yes, no). Crossover between treatment arms will not be allowed.
All patients will receive ARDS SOC following the official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline13 and/or the World Health Organization's (WHO's) clinical management of severe acute respiratory infection when COVID-19 disease is suspected (WHO Interim Guidance 202014 or other local guidance). Patients may continue receiving their corticosteroid (up to a cumulative maximum dexamethasone or equivalent dose of 60 mg [except to treat treatment-emergent reactions or comorbid conditions]) or antiviral therapy (except aminoquinoline compounds and convalescent plasma) at the same or lower doses if started at least 4 days (corticosteroid therapy) or at least 2 days (antiviral therapy) prior to randomization. Patients randomized to Arm A will additionally receive siltuximab 11 mg/kg IV administered over 1 hour, while patients randomized to Arm B will additionally receive IV NS administered over 1 hour, with opportunity to repeat their assigned study treatment once or twice at least 2 days apart on or after Day 3 as their clinical condition and/or laboratory testing dictate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a prospective, multicenter, randomized (2:1), double-blind, parallel-arm, placebo-controlled, Phase 3 clinical trial of 1-3 doses of siltuximab 11 mg/kg IV over 1 hour plus SOC vs. matched-volume normal saline (NS) IV over 1 hour plus SOC in 555 patients with SARS-CoV-2 previously treated with corticosteroids or another respiratory virus infection with elevated CRP levels who have developed serious respiratory complications
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: SiltuximabDrug - Siltuximab |
| Arm B | Other | Other: Normal SalineComparator - Normal Saline |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Positive microbiological evidence of SARS-CoV-2 or another respiratory virus infection (eg, other coronaviruses, respiratory syncytial virus, influenza virus) following institutional diagnostic standards
- Clinical and radiological diagnosis of pulmonary infection requiring noninvasive or mechanical invasive ventilatory support plus administration of rising supplemental oxygen concentrations
- Treatment of SARS-CoV-2-infected patients with dexamethasone (or equivalent) administered by mouth or intravenous (IV) injection
- Diagnosis of ARDS (PaO2/FiO2 ≤200 with positive end-expiratory pressure ≥5 cmH2O) in accordance with Berlin 2012 criteria1 (measured on or after the fourth day after the start of corticosteroid therapy in those patients for whom it was prescribed)
- Serum CRP level greater than upper limit of normal (measured on or after the third day after the start of corticosteroid therapy in those patients for whom it was prescribed) on 2 consecutive days
Key exclusion criteria (4 listed)
- Active bacterial or fungal infection, human immunodeficiency virus (HIV), HHV, Epstein-Barr virus, or other non-respiratory virus infection, or tuberculosis requiring initiation of anti-infective therapy
- Prior treatment with an agent targeting the IL-6 signaling pathway
- Current treatment in another therapeutic clinical trial (other than expanded remdesivir access protocol)
- Start of new immunosuppressive therapy (including but not limited to corticosteroids and cytokine signaling pathway inhibitors) within 4 days prior to study entry (randomization); start of new antiviral treatment (including but not limited to nucleoside analogues, aminoquinoline compounds, and convalescent plasma) within 2 days prior to randomization; or received a live vaccine at any time prior to randomization, or plan to receive a live vaccine during the study
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 |
|---|---|---|
| SiltuximabAlso: Sylvant11 mg/kg IV administered over 1 hour | Drug | Arm A |
| Normal SalineIV administered over 1 hour | Other | Arm B |
Primary outcome
28-day all-cause mortality
Time frame: Day 28
28-day all-cause mortality
14 secondary outcomes
Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)
Time frame: Up to 60 days
Ventilator-free days (VFDs) within 28 days
Time frame: Up to 28 days
Organ failure-free days (OFFD)
Time frame: Up to 60 days
Intensive care unit length of stay (ICU LOS)
Time frame: Up to 60 days
Hospital length of stay (HLOS)
Time frame: Up to 60 days
In-hospital all-cause mortality (IHACM)
Time frame: Up to 60 days
60-day all-cause mortality (60DACM)
Time frame: Up to 60 days
Time to oxygenation improvement (TOI)
Time frame: Up to 60 days
Duration of supplemental oxygen (DSO)
Time frame: Up to 60 days
Chest radiographic improvement (CRI)
Time frame: Up to 60 days
Time to National Early Warning Score 2 improvement (TNEWS2I)
Time frame: Up to 60 days
Treatment-emergent adverse events (TEAEs)
Time frame: Up to 60 days
Plasma siltuximab concentrations (PSCs)
Time frame: Up to 60 days
Anti-siltuximab antibodies (ASA)
Time frame: Up to 60 days
Results and safety
The study was stopped early (reason given: The REMAP-CAP and RECOVERY substudy results appear to support the survival benefit of tocilizumab in corticosteroid-treated or untreated patients with critically ill COVID-19-associated ARDS.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- 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.
Zainab Shahid, MD, Ph.D principal investigator
Participating Site
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Siltuximab and Normal Saline in people with Acute Respiratory Distress Syndrome and Lung Diseases, run by RECORDATI GROUP at 2 sites 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 6 inclusion and 4 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 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The REMAP-CAP and RECOVERY substudy results appear to support the survival benefit of tocilizumab in corticosteroid-treated or untreated patients with critically ill COVID-19-associated ARDS.). Results are not available in the source record.
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?
28-day all-cause mortality (time frame: Day 28). 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 19 Apr 2021.