Methodologies for Observational Studies Comparing Inpatient COVID-19 Treatments

NCT05638932 | Completed FDA Drug

• 1 other identifier: BAA1-RO3-20221202
• Study Type: observational
• Target: 1,442
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Inpatient mortality

  Inpatient mortality up to 28 days after IL6Ri or JAKi initiation

  up to 28 days after IL6Ri or JAKi initiation

Secondary Outcomes (1)

• Progression to IMV or ECMO

  up to 28 days after IL6Ri or JAKi initiation

Study Arms (1)

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

Drug: Initiation of IL6Ri (tocilizumab or sarilumab) versus JAKi (baricitinib or tofacitinib) added to systemic corticosteroids of interest (CSI)

Interventions

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)

Interleukin-6 receptor inhibitor (IL6Ri) initiators vs Janus kinase inhibitor (JAKi) initiators

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Aetion, Inc.: lead

Study Sites (1)

Aetion, Inc.

New York, New York, 10001, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

tocilizumab; sarilumab; baricitinib; tofacitinib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Vera Frajzyngier, PhD

  Aetion, Inc.

  PRINCIPAL INVESTIGATOR

• Liz M Garry, PhD

  Aetion, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Scientific Officer

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 6, 2022
• Study Start: June 16, 2020
• Primary Completion: September 25, 2023
• Study Completion: September 25, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)