Clinical Outcomes and Pharmacotherapy Effectiveness in the VA Health Care System (COPE-VA)

NCT06160128 | Recruiting

• 1 other identifier: 2038
• Study Type: observational
• Target: 400,000
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19, SARS-CoV-2 Infection; RSV; Influenza

Keywords

COVID-19; pharmacotherapy effectiveness; SARS-CoV-2; antiviral; RSV; influenza; respiratory viruses

Outcome Measures

Primary Outcomes (14)

• Receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir

  The odds of receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir were estimated using multivariable logistic regression

  January and February 2022

• Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days

  Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir- ritonavir versus molnupiravir.

  January through July 2022

• Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab)

  To analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).

  January 2022 through January 2023

• 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

  Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment.

  January through July 2022

• Incidence of any hospitalization or all-cause mortality at 30 days

  target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated Veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

  April 2022 through March 2023

• Prediction of 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications

  Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset.

  March 1, 2022, and March 31, 2023

• RSVPreF3 or RSVpreF vaccination compared with no RSV vaccination for the prevention of documented RSV infection and associated health-care use among Veterans

  The primary outcome was any positive RSV test result occurring from day 14 following the index date until the end of the study period.7,8 Secondary outcomes included RSV-associated emergency department or urgent care encounters, RSV-associated acute hospitalisations, RSV associated intensive care unit (ICU) admissions, and death. RSV-associated health-care encounters were defined as any corresponding encounter occurring the day before until 1 day after the eligible positive RSV test result. Death was defined as any death occurring on the day of until 30 days after the eligible positive RSV test result.

  March 1, 2022, and March 31, 2023

• compare disease severity of COVID-19, influenza, and RSV among US Veterans

  This retrospective cohort study analyzed national US Veterans Health Administration electronic health record data of nonhospitalized Veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024. Following inverse probability weighting, the cumulative incidence and risk differences (RDs) were calculated for the primary outcomes of 30-day hospitalization, intensive care unit admission, and death, as well as the secondary outcome of long-term death extending through 180 days.

  August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024.

• Determine XBB.1.5 COVID-19 VE and the extent to which it declines over time

  Outcomes were ascertained through 10 May 2024 and included any positive result on a SARS-CoV-2 test from day 10 after the matched index date, subsequent hospitalization within 1 day before or 10 days after the positive result, or death within 30 days after the positive result. Vaccine effectiveness was estimated as 100x (1-risk ratio).

  October 2,2023- January 3, 2024

• 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

  Investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of selected PCCs or death up to 1 year after infection, separately in the wild-type (WT), Alpha-transition, Delta, and Omicron eras and by vaccination status.

  March 2020 and April 2022

• Determined budget cost of providing nirmatrelvir-ritonavir to Veterans with COVID-19 on 30-day healthcare costs to inform procurement strategies in large healthcare systems

  The decision tree analysis included transition states from cohort entry (ie, infection and treatment) to ED visit, hospitalization without ICU admission, hospitalization with ICU admission, recovery, and death (Figure 1). Decision trees were created for each subgroup and treatment allocation and parameterized with subgroup and treatment specific transition probabilities. In total, 26 trees (13 subgroups and 2 treatment scenarios) were created and parameterized with over 150 transition probabilities.

  April 2022 through March 2023

• Evaluate the impact of different time zero designations on results and inferences from a cohort study comparing the effectiveness of nirmatrelvir ritonavir treatment versus no COVID-19 antiviral treatment in preventing 30-day hospitalization and death

  Identified US Veterans who tested positive for SARS-CoV-2 from April 2022-March 2023 and compared nirmatrelvir-ritonavir versus no treatment using 5 time zero approaches: test-date (treated) versus test-date (untreated) with matching allowing treatment on days 0-5 (approach 1a) or day 0 only (1b), test-date versus test-date with a clone-censor-weight method (1c), treatment date versus test-date (2) with matching, or treatment date versus matched index date (3).

  April 2022-March 2023

• Asses the long-term effectiveness of a single respiratory syncytial virus (RSV) vaccine dose against RSV illness and associated health care use

  The primary outcome was any positive RSV test result from day 14 following the matched index date. Secondary outcomes included RSV-associated emergency department or urgent care visits, hospitalizations, or intensive care unit admissions. Vaccine effectiveness was estimated as 100 × (1 - risk ratio).

  September 2023 to March 2024.

• Estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration

  Vaccine effectiveness against documented SARS CoV-2 infection, SARS-CoV-2 associated ED/UC visit, SARS-CoV-2 associated hospitalization or SARS-CoV-2 associated death

  August 1, 2024- April 12, 2025

Study Arms (4)

Outpatient Veterans with risk factors for severe COVID-19 & tested positive during Jan-Feb 2022

This cohort study assessed outpatient Veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022. The purpose is to describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Affairs (VA) health care system.

Nonhospitalized Veterans in VHA at risk for SARS-CoV-2 Jan-Jul 2022

Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir- ritonavir versus molnupiravir. The purpose is to measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.

Outpatient Veterans who tested positive for SARS-CoV-2 from Jan 2022 through Jan 2023

This cohort study evaluated nonhospitalized Veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023 using VHA and linked Community Care and Medicare databases. The purpose is to analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).

Outpatient Veterans with risk factors for severe COVID-19 & tested positive during Jan-Jul 2022

Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment. The purpose is to measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing Post COVID conditions.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.

You may not qualify if:

• VA employees who are not enrollees

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Biomedical Advanced Research and Development Authority: collaborator
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

RECRUITING

Biospecimen

Retention: NONE RETAINED

none collected or retained

MeSH Terms

Conditions

COVID-19; Influenza, Human

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; Orthomyxoviridae Infections

Study Officials

• Kristina L Bajema, MD

  VA Portland Health Care System, Portland, OR

  STUDY CHAIR

• George N. Ioannou, MD MS

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  STUDY CHAIR

Central Study Contacts

Kristina L Bajema, MD

CONTACT

(503) 220-8262; Kristina.Bajema@va.gov

George N Ioannou, MD MS

CONTACT

(206) 277-3136; George.Ioannou@va.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 7, 2023
• Study Start: September 26, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)