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

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
• Healthy volunteers accepted
• Adult, Older adult

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

About this study

Official title: CSP #2038 - COVID-19 Pharmacotherapy Effectiveness in the VA Healthcare System (COPE-VA)

Conditions

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

Keywords

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

Medical subject headings

COVID-19, Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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

   Measured: January and February 2022

2. 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.

   Measured: January through July 2022

3. 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).

   Measured: January 2022 through January 2023

4. 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.

   Measured: January through July 2022

5. 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)

   Measured: April 2022 through March 2023

6. 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. The investigators created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. The investigators 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.

   Measured: March 1, 2022, and March 31, 2023

7. RSVPreF3 or RSVpreF vaccination compared with no respiratory syncytial virus (RSV) vaccination for the prevention of documented RSV infection and associated health-care use among Veterans

   The primary outcome was any positive respiratory syncytial virus (RSV) test result occurring from day 14 following the index date until the end of the study period. Secondary outcomes included RSV-associated emergency department or urgent care encounters, RSV-associated acute hospitalizations, 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.

   Measured: March 1, 2022, and March 31, 2023

8. 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 non-hospitalized 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.

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

9. Determine XBB.1.5 COVID-19 vaccine effectiveness (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).

   Measured: October 2,2023- January 3, 2024

10. 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.

    Measured: March 2020 and April 2022

11. 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 (i.e., infection and treatment) to emergency department (ED) visit, hospitalization without intensive care unit (ICU) admission, hospitalization with ICU admission, recovery, and death. 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.

    Measured: April 2022 through March 2023

12. 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).

    Measured: April 2022-March 2023

13. 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).

    Measured: September 2023 to March 2024.

14. 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

    Measured: August 1, 2024- April 12, 2025

15. Compared treatment with oseltamivir versus no antiviral treatment within 6 hours of a positive influenza test

    Assessed Veterans who presented to emergency departments in the Veterans Health Administration (VHA) and tested positive for influenza

    Measured: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024

16. Calculated cumulative incidence, risk differences (RDs), and risk ratios (RR) for hospitalization and intensive care unit (ICU) admission at 10 days

    Assessed Veterans who presented to emergency departments in the Veterans Health Administration (VHA) and tested positive for influenza

    Measured: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024

17. Calculated cumulative incidence, risk differences (RDs), and risk ratios (RR) for hospitalization and intensive care unit (ICU) admission at death at 30 days

    Assessed Veterans who presented to emergency departments in the Veterans Health Administration (VHA) and tested positive for influenza

    Measured: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted7 Dec 2023
2. Study start26 Sep 2022
3. Primary completion30 Sep 2027 (estimated)
4. Study completion30 Sep 2027 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Other trials for COVID-19, SARS-CoV-2 InfectionStudies of the same condition, open and under way.
• More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
• 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.