Clinical trial NCT06160128: Clinical Outcomes and Pharmacotherapy Effectiveness in the VA Health Care System (COPE-VA)
Official title: CSP #2038 - COVID-19 Pharmacotherapy Effectiveness in the VA Healthcare System (COPE-VA)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: COVID-19, SARS-CoV-2 Infection
RSV
Influenza
Keywords: COVID-19
pharmacotherapy effectiveness
SARS-CoV-2
antiviral
RSV
influenza
respiratory viruses
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Biomedical Advanced Research and Development Authority
name: Food and Drug Administration (FDA)
First posted: 2023-12-07
Enrollment: 400000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: VA enrollees infected from January 1, 2022 through February 28, 2022 as an example. Subsequent trials will be executed as the pandemic evolves

Brief summary: The purpose of this study is to comprehensively describe the temporal and geographic utilization of COVID-19 therapies used for mild to moderate disease during different periods of SARS-CoV-2 variant circulation as well as to compare demographic and clinical characteristics of Veterans who are treated or do not receive these different therapies. The investigators will also perform similar descriptive epidemiology for other respiratory viruses, including RSV and influenza and other infectious diseases. This first phase will critically inform feasibility and direction of the second phase, in which the investigators will use target trial emulation design to study the comparative effectiveness of therapies and vaccines for COVID-19, respiratory viruses, including RSV, and influenza, and other infectious diseases.

Detailed description: Objectives:

This study will be completed in two phases. In the first phase, the investigators will establish a source population and comprehensively describe the temporal and geographic utilization of COVID-19 pharmacotherapies beginning July 2021. These therapies include casirivimab and imdevimab, bamlanivimab and etesevimab, sotrovimab, nirmatrelvir, molnupiravir, and remdesivir. The investigators will also compare demographic and clinical characteristics of Veterans who are treated or do not receive these therapies. Phase 1 will inform the study design and analytic protocol of Phase 2. Phase 1 will also inform critical policy questions and national guidance regarding COVID-19 pharmacotherapies in the VA healthcare system with the potential to inform policy across other healthcare systems.

In the second phase, the investigators will conduct target trial emulation studies to determine the effectiveness and comparative effectiveness of current pharmacotherapies for COVID-19 in preventing short- and long-term adverse outcomes related to SARS-CoV-2 infection. The investigators will use a sequence of comparative effectiveness studies through emulation to help establish a common framework sharing a similar population, design, and outcomes for a rapid-response, adaptive observational study design to characterize utilization and determine the effectiveness and comparative effectiveness of novel therapeutic agents authorized for the treatment of mild to moderate COVID-19 in Veterans. Phase 2 will provide an infrastructure upon which subsequent observational studies can be performed, which will include other infectious diseases of interest, ultimately ensuring the timeliness and pertinence of VA research.

Research Design and Methodology:

In the first phase, the investigators will conduct a descriptive, retrospective, electronic health record-based study among Veterans aged 18 years with a laboratory-confirmed positive test for SARS-CoV-2 or a diagnosis of COVID-19 documented at any time since the beginning of the pandemic in January 2020 to present. The investigators will describe the geographic distribution (by VISN, state, and distance from place of residence to the closest VAMC and/ COVID-19 infusion facilities) of Veterans receiving each of the COVID-19 antiviral and monoclonal antibody therapies during different periods of SARS-CoV-2 variant circulation (i.e., January 1, 2022, to present for Omicron). The investigators will also compare baseline demographic characteristics, clinical characteristics including underlying medical conditions and prior SARS-CoV-2 infections, SARS-CoV-2 vaccination status, National Institutes of Health (NIH) risk group tiers for prioritization of treatments, concurrent outpatient medications, and time from positive test to treatment among Veterans receiving different antiviral and monoclonal antibody therapies as well as eligible Veterans who are not treated during different periods of SARS-CoV-2 variant circulation. This established framework will also be used to identify Veterans who tested positive for other respiratory viruses, including influenza virus or respiratory syncytial virus (RSV), and other infectious diseases in the same time period and describe their characteristics, risk factors and treatments.

In the second phase, the investigators will conduct retrospective and prospective target trial emulation studies to evaluate the effectiveness and comparative effectiveness of different pharmacotherapies for mild-to-moderate COVID-19 in patients with documented SARS-CoV-2 infection by period of predominant SARS-CoV-2 variant circulation. The established framework will be used to investigate vaccine and pharmacotherapy effectiveness for SARS-CoV-2 and other respiratory viruses, including influenza and respiratory syncytial virus (RSV) and other infectious diseases using observational data from the VHA electronic health records.

Impact Significance:

Data on real-world utilization and clinical outcomes in the Veteran population are needed to inform clinical, operational and research partners in the VA and other healthcare systems on strategies for optimizing the utilization of pharmacotherapies and vaccines against COVID-19 and other infectious diseases. Ongoing evaluations will be essential as new variants emerge, vaccination practices evolve, and new pharmacotherapies are introduced. This study will establish a common framework sharing a similar population, design, and outcomes for a rapid-response, adaptive platform observational study design to characterize utilization and determine the effectiveness and comparative effectiveness of novel therapeutic agents authorized for the treatment of mild to moderate COVID-19, respiratory viruses, including RSV and influenza, and other infectious diseases in Veterans.

Eligibility criteria: Inclusion Criteria:

Phase 1:

- Veterans aged 18 years with a laboratory-confirmed positive test for SARS-CoV-2 or a diagnosis of COVID-19 documented at any time since the beginning of the pandemic in January 2020 to present.

Phase 2:

* All Veterans aged 18 years alive and in VHA care as of January 2018.
* Specific exclusion/inclusion criteria and observation periods will be further defined for each sub-study (See outcomes/publications).

Exclusion Criteria:

* VA employees who are not enrollees

Primary outcomes:
measure: Receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir
timeFrame: January and February 2022
measure: Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days
timeFrame: January through July 2022
measure: Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab)
timeFrame: January 2022 through January 2023
measure: Cumulative incidence of 31 potential PCCs at 31 -180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions
timeFrame: January through July 2022
measure: Incidence of any hospitalization or all-cause mortality at 30 days
timeFrame: April 2022 through March 2023
measure: Prediction of 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications
timeFrame: March 1, 2022, and March 31, 2023
measure: RSVPreF3 or RSVpreF vaccination compared with no RSV vaccination for the prevention of documented RSV infection and associated health-care use among Veterans
timeFrame: March 1, 2022, and March 31, 2023
measure: compare disease severity of COVID-19, influenza, and RSV among US Veterans
timeFrame: August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024.
measure: Determine XBB.1.5 COVID-19 VE and the extent to which it declines over time
timeFrame: October 2,2023- January 3, 2024
measure: Determine if severe SARS-CoV-2 infection increases risk of selected PCCs or death up to 1 year after infection in wild-type (WT), Alpha-transition, Delta, and Omicron eras
timeFrame: March 2020 and April 2022
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Kristina L Bajema, MD
role: STUDY_CHAIR
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: George N. Ioannou, MD MS
role: STUDY_CHAIR
References: