COVID-19NCT05638932
Methodologies for Observational Studies Comparing Inpatient COVID-19 Treatments
An observational study of COVID-19, run by Aetion, Inc. at 1 site in United States.
Trial summary
To apply and compare two different methodological approaches (one applying diagnostics steps and contingencies and the other not) to the illustrative example described below: Illustrative Example - Objective I aims to characterize the risk of inpatient mortality [Primary Outcome] and progression to invasive mechanical… 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?
- Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)
- How many people
- 1,442 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2020to 25 Sep 2023
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The overall cohort for our Illustrative Example will consist of insured adults hospitalized with COVID-19 between June 16, 2020 to February 01, 2022 who require supplemental oxygen or ventilation support and initiate either IL6Ri (TCZ or SAR) or JAKi (BAR or TOF) in addition to systemic CSIs within 4 days after hospital admission. All patients will be required to have at least one procedure for oxygen supplementation and at least one recorded CSI administration from admission to treatment initiation, since during the study period IL6Ri and JAKi were only indicated for patients receiving CSIs and some level of oxygen or ventilation support.
Who may be able to join
- Hospitalized from June 16, 2020 to February 01, 2022 with an international classification of diseases (ICD)-10 diagnosis code of U07.1 in an any admitting diagnosis position (Day 0)
- Initiate either IL6Ri or JAKi within 4 days after hospital admission (Days 0 to 4)
- Receiving systemic CSI on day of IL6Ri/JAKi initiation (Day T)
- Receipt of at least one respiratory support procedure (oxygen supplementation at a minimum) from admission to IL6Ri/JAKi initiation (Days 0 to T)
- For Illustrative Example - Objective I only:
- -maximum modified World Health Organization (mWHO) disease severity of O2/NIV/HFO from admission to IL6Ri/JAKi initiation (Days 0 to T)
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- For Illustrative Example - Objective II only:
- Admission to ICU at hospital admission (Day 0) and mWHO disease severity of IMV/ECMO from hospital/ICU admission to IL6Ri/JAKi initiation (Days 0 to T)
- Continuous medical claims enrollment (60-day gaps permitted) during the 183 day baseline period prior to and including hospital or ICU admission (Days -183 to 0) to minimize the potential for misclassification of baseline covariates
Who cannot join
- Exclude patients without continuous medical claims enrollment (60-day gaps permitted) during the 183-day baseline period prior to and including hospital/ICU admission (Days -183 to 0) to minimize the potential for misclassification of baseline covariates.
- Exclude patients if COVID-19 hospitalization (Day 0) begins >14 days after initial COVID-19 diagnosis. Patients will be excluded if any COVID-19 diagnosis is recorded from 90 days to 15 days before admission (Days -90 to -15) to exclude patients with possible long-term COVID or post-acute sequelae while still permitting prior infections recorded more than 90 days pre-admission.
- No age, sex, or geographic region recorded on hospital admission (Day 0)
- Age less than 18 years at hospital admission (Day 0)
- Evidence of a prior COVID-related inpatient hospitalization in the previous 14 days (Days -14 to -3), with a two-day buffer to permit brief inpatient utilization directly proceeding transfer to a chargemaster hospital (i.e., inpatient utilization permitted on Days -2 to -1)
- Systemic CSI use (dispensing or remaining supply) in the previous 14 days (Days -14 to -3), with a two-day buffer to permit CSI use beginning in the emergency department or other healthcare setting immediately prior to chargemaster hospital admission (CSI use permitted Days -2 to -1)
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- Any recorded use of IL6Ri or JAKi (dispensing or remaining supply) in the 90-day washout period before IL6Ri or JAKi initiation (Days -90 to T-1), to satisfy new use definition
- Baseline receipt of oxygen or ventilation support for non-COVID conditions (e.g., supplemental oxygen for COPD), defined as two or more respiratory support procedures recorded on different days from Days -90 to -15 via procedure codes from medical claims, chargemaster, and where available, oxygen supplies recorded in pharmacy settings.
- Death or discharge occurs before or on the day of treatment initiation (Days 0 to T)
- Recorded use of both IL6Ri and JAKi on Day T
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Methodologies for Observational Studies Comparing Inpatient COVID-19 Treatments: IL-6 Receptor Inhibitors and JAK Inhibitors for Hospitalized COVID-19 Patients Receiving Corticosteroid Therapy
To apply and compare two different methodological approaches (one applying diagnostics steps and contingencies and the other not) to the illustrative example described below:
Illustrative Example - Objective I aims to characterize the risk of inpatient mortality [Primary Outcome] and progression to invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) [Secondary Outcome] up to 28 days after interleukin-6 receptor inhibitors (IL6Ri) or janus kinase inhibitor (JAKi) initiation among patients hospitalized with Coronavirus Disease 2019 (COVID-19) who initiate a corticosteroid of interest and require supplemental oxygen / non-invasive ventilation / high flow oxygen (O2/NIV/HFO) (but not IMV/ECMO).
Read more
Illustrative Example - Objective II aims to characterize the risk of inpatient mortality [Primary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients admitted to the ICU at hospital admission with COVID-19 who initiate a CSI and require IMV/ECMO.
Hazard ratios (HR) and corresponding 95% confidence intervals (CI) will be estimated and reported for all outcome risks in Illustrative Example objectives.
Read the detailed description
In this study we seek to evaluate current methodologies for observational comparative studies of inpatient COVID-19 treatments [Overall Study Objective]. To support this overall study objective, we have defined additional supporting objectives related to the research process [Process Objectives] as applied to an illustrative example of an observational study to evaluate the comparative effectiveness of inpatient COVID-19 treatments [Illustrative Example].
Process Objectives:
Characterize differences in study results when an intentional multiphase approach (IMA) to diagnostics and contingencies is applied to real world data (RWD) analysis compared to an approach that pre-specifies all covariates and statistical approaches without consideration of whether key statistical assumptions hold (Single-phase Prespecification Approach, SPA).
Illustrative Example:
Our illustrative example will use a large population-based US claims data source to emulate a hypothetical target trial to assess the comparative effectiveness of IL6Ri (TCZ or SAR) versus JAKi (BAR or TOF) added to systemic corticosteroids of interest (CSI). The underlying hypothetical target trial of interest consists of patients hospitalized and requiring respiratory support for COVID-19 and receiving a CSI who are assigned to receive either an IL6Ri or JAKi in addition to CSI within 4 days after hospital/ICU admission. The patients are followed for up to 28 days for the outcomes of inpatient mortality and progression to IMV/ECMO. The Illustrative Example is separated into two sub-objectives based on the different COVID-19 severity populations of interest.
Illustrative Example - Objective I aims to characterize the risk of inpatient mortality [Primary Outcome] and progression to IMV or ECMO [Secondary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients hospitalized with COVID-19 who initiate a CSI and require supplemental O2/NIV/HFO (but not IMV/ECMO).
Illustrative Example - Objective II aims to characterize the risk of inpatient mortality [Primary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients admitted to the ICU at hospital admission with COVID-19 who initiate a CSI and require IMV/ECMO.
Hazard ratios (HR) and corresponding 95% confidence intervals (CI) will be estimated and reported for all outcome risks in Illustrative Example objectives.
- Conditions
- COVID-19
- Being tested
- Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)Drug
Real world use of either IL6Ri (TCZ or SAR) or JAKi (BAR or TOF)
| Study group | Role | What they receive |
|---|---|---|
| Interleukin-6 receptor inhibitor (IL6Ri) initiators vs Janus kinase inhibitor (JAKi) initiators | Hospitalized patients who initiate an IL6Ri versus JAKi in addition to a corticosteroid of interest Receives: Drug: Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inpatient mortality
Inpatient mortality up to 28 days after IL6Ri or JAKi initiation
Measured: up to 28 days after IL6Ri or JAKi initiation
Secondary outcomes (1)
Progression to IMV or ECMO
Progression to IMV or ECMO up to 28 days after IL6Ri or JAKi initiation (Illustrative Example - Objective I only)
Measured: up to 28 days after IL6Ri or JAKi initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start16 Jun 2020
- Primary completion25 Sep 2023
- Study completion25 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,442 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aetion, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicolle Gatto, Aetion, Inc.
- Investigators
- Vera Frajzyngier, PhD, Principal investigator, Aetion, Inc.Liz M Garry, PhD, Principal investigator, Aetion, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05638932
- Sponsor's protocol ID
- BAA1-RO3-20221202
- Status last verified
- Sep 2024
- First submitted
- 2 Dec 2022
- Last updated
- 19 Sep 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Study results will report aggregated findings
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methodologies for Observational Studies Comparing Inpatient COVID-19 Treatments: IL-6 Receptor Inhibitors and JAK Inhibitors for Hospitalized COVID-19 Patients Receiving Corticosteroid Therapy
- ClinicalTrials.gov ID
- NCT05638932
- Acronym / sponsor ID
- BAA1-RO3-20221202
- Conditions
- COVID-19
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,442 participants (actual)
- Lead sponsor
- Aetion, Inc.University, hospital or other
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 25 Sep 2023 (actual)
- Study completion
- 25 Sep 2023 (actual)
- First posted
- 6 Dec 2022 (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.
To apply and compare two different methodological approaches (one applying diagnostics steps and contingencies and the other not) to the illustrative example described below:
Illustrative Example - Objective I aims to characterize the risk of inpatient mortality [Primary Outcome] and progression to invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) [Secondary Outcome] up to 28 days after interleukin-6 receptor inhibitors (IL6Ri) or janus kinase inhibitor (JAKi) initiation among patients hospitalized with Coronavirus Disease 2019 (COVID-19) who initiate a corticosteroid of interest and require supplemental oxygen / non-invasive ventilation / high flow oxygen (O2/NIV/HFO) (but not IMV/ECMO).
Illustrative Example - Objective II aims to characterize the risk of inpatient mortality [Primary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients admitted to the ICU at hospital admission with COVID-19 who initiate a CSI and require IMV/ECMO.
Hazard ratios (HR) and corresponding 95% confidence intervals (CI) will be estimated and reported for all outcome risks in Illustrative Example objectives.
Detailed description
In this study we seek to evaluate current methodologies for observational comparative studies of inpatient COVID-19 treatments [Overall Study Objective]. To support this overall study objective, we have defined additional supporting objectives related to the research process [Process Objectives] as applied to an illustrative example of an observational study to evaluate the comparative effectiveness of inpatient COVID-19 treatments [Illustrative Example].
Process Objectives:
Characterize differences in study results when an intentional multiphase approach (IMA) to diagnostics and contingencies is applied to real world data (RWD) analysis compared to an approach that pre-specifies all covariates and statistical approaches without consideration of whether key statistical assumptions hold (Single-phase Prespecification Approach, SPA).
Illustrative Example:
Our illustrative example will use a large population-based US claims data source to emulate a hypothetical target trial to assess the comparative effectiveness of IL6Ri (TCZ or SAR) versus JAKi (BAR or TOF) added to systemic corticosteroids of interest (CSI). The underlying hypothetical target trial of interest consists of patients hospitalized and requiring respiratory support for COVID-19 and receiving a CSI who are assigned to receive either an IL6Ri or JAKi in addition to CSI within 4 days after hospital/ICU admission. The patients are followed for up to 28 days for the outcomes of inpatient mortality and progression to IMV/ECMO. The Illustrative Example is separated into two sub-objectives based on the different COVID-19 severity populations of interest.
Illustrative Example - Objective I aims to characterize the risk of inpatient mortality [Primary Outcome] and progression to IMV or ECMO [Secondary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients hospitalized with COVID-19 who initiate a CSI and require supplemental O2/NIV/HFO (but not IMV/ECMO).
Illustrative Example - Objective II aims to characterize the risk of inpatient mortality [Primary Outcome] up to 28 days after IL6Ri or JAKi initiation among patients admitted to the ICU at hospital admission with COVID-19 who initiate a CSI and require IMV/ECMO.
Hazard ratios (HR) and corresponding 95% confidence intervals (CI) will be estimated and reported for all outcome risks in Illustrative Example objectives.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interleukin-6 receptor inhibitor (IL6Ri) initiators vs Janus kinase inhibitor (JAKi) initiators | – | Drug: Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)Hospitalized patients who initiate an IL6Ri versus JAKi in addition to a corticosteroid of interest |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The overall cohort for our Illustrative Example will consist of insured adults hospitalized with COVID-19 between June 16, 2020 to February 01, 2022 who require supplemental oxygen or ventilation support and initiate either IL6Ri (TCZ or SAR) or JAKi (BAR or TOF) in addition to systemic CSIs within 4 days after hospital admission. All patients will be required to have at least one procedure for oxygen supplementation and at least one recorded CSI administration from admission to treatment initiation, since during the study period IL6Ri and JAKi were only indicated for patients receiving CSIs and some level of oxygen or ventilation support.
Key inclusion criteria (9 listed)
- Hospitalized from June 16, 2020 to February 01, 2022 with an international classification of diseases (ICD)-10 diagnosis code of U07.1 in an any admitting diagnosis position (Day 0)
- Initiate either IL6Ri or JAKi within 4 days after hospital admission (Days 0 to 4)
- Receiving systemic CSI on day of IL6Ri/JAKi initiation (Day T)
- Receipt of at least one respiratory support procedure (oxygen supplementation at a minimum) from admission to IL6Ri/JAKi initiation (Days 0 to T)
- -maximum modified World Health Organization (mWHO) disease severity of O2/NIV/HFO from admission to IL6Ri/JAKi initiation (Days 0 to T)
Key exclusion criteria (10 listed)
- Exclude patients without continuous medical claims enrollment (60-day gaps permitted) during the 183-day baseline period prior to and including hospital/ICU admission (Days -183 to 0) to minimize the potential for misclassification of baseline covariates.
- Exclude patients if COVID-19 hospitalization (Day 0) begins >14 days after initial COVID-19 diagnosis. Patients will be excluded if any COVID-19 diagnosis is recorded from 90 days to 15 days before admission (Days -90 to -15) to exclude patients with possible long-term COVID or post-acute sequelae while still permitting prior infections recorded more than 90 days pre-admission.
- No age, sex, or geographic region recorded on hospital admission (Day 0)
- Age less than 18 years at hospital admission (Day 0)
- Evidence of a prior COVID-related inpatient hospitalization in the previous 14 days (Days -14 to -3), with a two-day buffer to permit brief inpatient utilization directly proceeding transfer to a chargemaster hospital (i.e., inpatient utilization permitted on Days -2 to -1)
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 |
|---|---|---|
| Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)Real world use of either IL6Ri (TCZ or SAR) or JAKi (BAR or TOF) | Drug | Interleukin-6 receptor inhibitor (IL6Ri) initiators vs Janus kinase inhibitor (JAKi) initiators |
Primary outcome
Inpatient mortality
Time frame: up to 28 days after IL6Ri or JAKi initiation
Inpatient mortality up to 28 days after IL6Ri or JAKi initiation
1 secondary outcome
Progression to IMV or ECMO
Time frame: up to 28 days after IL6Ri or JAKi initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No. Study results will report aggregated findings
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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.
Vera Frajzyngier, PhD principal investigator
Aetion, Inc.
Liz M Garry, PhD principal investigator
Aetion, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by Aetion, Inc. 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 9 inclusion and 10 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: finished, as of the sponsor's last update on 19 Sep 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Inpatient mortality (time frame: up to 28 days after IL6Ri or JAKi initiation). 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 Sep 2024.