A Study to Learn About ABRYSVO Vaccine in Older Adults to Prevent Severe Respiratory Syncytial Virus (RSV) Disease
- Conditions
- Respiratory Syncytial Viruses
- Interventions
- Biological: Prior standard of care receipt of Pfizer's ABRYSVO vaccine
- Registration Number
- NCT06077968
- Lead Sponsor
- Pfizer
- Brief Summary
The main purpose of this study is to learn about the effectiveness of Pfizer's ABRYSVO vaccine. This vaccine helps to prevent infections caused by Respiratory Syncytial Virus (RSV). RSV is a virus that can cause infections in the airways. These symptoms can be cold-like symptoms, but in some cases can lead to severe symptoms or hospitalization.
This study uses only healthcare data that are already collected from routine visits to healthcare providers. This means that participants will not be actively enrolled in the study and there are no study treatments. The study will look at data for about two years. This study will look at patient information from:
* Adults ages 60 years and older
* Adults who are eligible to receive the ABRYSVO vaccination
Substudy A:
* This study will assess the duration of protection of ABRYSVO in adults ages 60 years and older after completion of the original study.
* The substudy will look at data from subsequent RSV seasons after the first dose of ABRYSVO for about 3 years.
Substudy B:
* This study will assess vaccine effectiveness of ABRYSVO after revaccination in routine use, pending ACIP recommendation for revaccination.
* The substudy will look at data for about 2 years after revaccination.
- Detailed Description
The primary objective of this retrospective study is to estimate vaccine effectiveness of Pfizer's ABRYSVO vaccine against RSV-related lower respiratory tract disease (LRTD) requiring hospitalization among Kaiser Permanente Southern California members who are eligible for vaccination per current recommendations from the Advisory Committee on Immunization Practices (ACIP). Analyses will employ a retrospective case-control study with test negative design (TND) and a retrospective cohort design. The TND will assess RSV-related outcomes, while the cohort design will assess all-cause outcomes. The cohort study may also assess RSV-related outcomes, depending on RSV testing rates. Standard of care (SOC) RSV testing and re-testing of remnant SOC respiratory specimens for those who did not have SOC testing will be used to define RSV-related endpoints. For the cohort design, a sensitivity analysis including imputation of results for individuals experiencing lower respiratory tract disease without confirmation of RSV positivity or negativity may also be conducted. In the event that standard of care testing practices decline or there are not enough available specimens for estimating RSV-associated VE, the study may be extended to additional seasons. Secondary objectives of the TND, and if conducted for RSV-related endpoints, of the cohort study, include estimating vaccine effectiveness against: RSV-related LRTD hospitalizations among immunocompetent, RSV-related lower respiratory tract disease hospitalizations among high-risk groups, RSV-related acute respiratory tract infection hospitalizations, and Emergency Department (ED) visits. The retrospective cohort analysis will provide VE estimates against additional all-cause ARI and LRTD outcomes, as well as incidence rates and rate reductions for study outcomes, and will include outpatient outcomes. Analyses will include stratifications by presence of comorbidity, RSV subgroup, severity, age, frailty, and other selected demographic factors.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1
Test Negative Design:
- KPSC patients eligible to receive ABRYSVO per current ACIP recommendations who are admitted to the hospital with ARI/LRTD, (defined using International Classification of Diseases (ICD) codes listed in Annex 2 Table 1) after start of study period, and who have had an RSV test, either through standard of care testing or blinded study testing of remnant respiratory specimens.
- For secondary objectives estimating VE against ED admission, the TND will include KPSC patients eligible to receive ABRYSVO who present to the ED with ARI/LRTD after start of study period, and who have had an RSV test, either through standard of care testing or blinded study testing of remnant respiratory specimens.
- For exploratory objectives estimating VE against RSV-related cardiac hospitalization, the TND will include KPSC patients eligible to receive ABRYSVO® who are hospitalized or present to the ED with cardiac events (defined using ICD codes listed in Annex 2 Table 3) after start of study period, and who have had an RSV test, either through SOC testing or blinded study testing of remnant respiratory specimens.
- We will include membership requirement of 1 year prior to index date, which is defined as the date of hospitalization or ED admission (allowing 45-day administrative gap), to facilitate accurate capture of comorbid conditions.
Retrospective Cohort Design:
- All KPSC members eligible to receive ABRYSVO as of start of study period.
- For the cohort study, patients must have at least 1 year of membership (allowing 45-day administrative gap) prior to start of study period (index date) to facilitate accurate capture of comorbid conditions.
Patients meeting any of the following criteria will not be included in the study:
Test Negative Design:
We will exclude patients who receive another licensed or investigational RSV vaccine prior to hospitalization or ED visit from the study population and analysis. Patients will be excluded if the index date is within certain time windows from vaccination date, outlined further in the exposure section below.
Cohort Design:
Patients will be excluded if they receive any other licensed or investigational RSV vaccine prior to study start; patients will be censored for receiving any other licensed or investigational RSV vaccine during the study period.
SSA and SSB Eligibility Criteria:
The inclusion criteria for Substudy A are described above for the Test Negative Design.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Unvaccinated Prior standard of care receipt of Pfizer's ABRYSVO vaccine Patients will be considered unvaccinated if they do not have documented evidence of receiving ABRYSVO. Vaccinated Prior standard of care receipt of Pfizer's ABRYSVO vaccine Patients will be considered vaccinated if they have documented evidence of receiving ABRYSVO ≥21 days before index date (i.e., defined as the date of hospitalization or Emergency Department (ED) admission.)
- Primary Outcome Measures
Name Time Method Test Negative Design (TND) 1. Vaccine Effectiveness (VE) calculated as 1 minus the odds ratio (OR) comparing the odds of being vaccinated with ABRYSVO for RSV-related hospitalized LRTD cases and controls, multiplied by 100%. Up to 2 years Adjusted for confounding factors using logistic regression. To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations
- Secondary Outcome Measures
Name Time Method SSA Secondary 3: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO® for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, using LRTD events from the 5th season Up to 3 years Among those with 5 completed RSV seasons after vaccination with a single dose ABRYSVO®, to estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations during 5th RSV season after a single dose
TND Secondary 1: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for RSV-related LRTD hospitalizations among immunocompetent cases and controls, multiplied by 100%. Adjusted for confounding using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations among the immunocompetent.
TND Secondary 2: ABRYSVO VE estimates stratified by age groups. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations, stratified by age.
TND Secondary 3: ABRYSVO VE estimates stratified by virus subgroups. Adjusted for confounding factors using logistic regression. Up to 2 years To further describe the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations, stratified by RSV subgroup (A and B)
TND Secondary 4: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for RSV-related severe LRTD cases and controls, multiplied by 100%. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related severe LRTD.
TND Secondary 5: ABRYSVO VE estimates stratified by frailty index. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalization stratified by frailty index
TND Secondary 6: ABRYSVO VE estimates stratified by chronic medical condition risk category. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations, stratified by chronic medical condition risk category (3 strata: not high-risk conditions, immunocompromising high-risk conditions, non-immunocompromising high-risk conditions).
TND Secondary 7: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, among those with CHF and COPD. Up to 2 years Adjusted for confounding factors using logistic regression. Among those with CHF and COPD, to estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations
TND Secondary 8-1: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for ED (without subsequent hospitalization) cases and controls, multiplied by 100%. Up to 2 years Adjusted for confounding factors using logistic regression. To estimate the effectiveness of ABRYSVO against ED admission (without subsequent hospitalization)
TND Secondary 8-2: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for hospitalized or ED visit (without subsequent hospitalization) cases and controls, multiplied by 100%. Up to 2 years Adjusted for confounding factors using logistic regression. To estimate the effectiveness of ABRYSVO against ED (without subsequent hospitalization) or hospitalization, for RSV-related LRTI separately
TND Secondary 9: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for RSV-related death cases and controls, multiplied by 100%. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related death
TND Secondary 10: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO for hospitalized RSV-related ARI cases and controls, multiplied by 100%. Adjusted for confounding factors using logistic regression. Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related ARI hospitalization
TND Secondary 11: Describe age, sex, race/ethnicity, clinical and lab characteristics, and disease severity of any patients who received ABRYSVO and tested positive for RSV Up to 2 years To describe demographic, clinical, and laboratory characteristics and disease severity of any RSV events among vaccinated individuals
TND Secondary 12: ABRYSVO® RSV-related VE estimates stratified by age group and chronic medical risk categories Up to 2 years To estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations, stratified by age group and chronic medical risk categories
Cohort Secondary 1: VE calculated as 1 minus the hazard ratio (HR) comparing the incidence of all-cause LRTD hospitalization among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100%. Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause LRTD hospitalizations
Cohort Secondary 2: ABRYSVO® all-cause VE estimates stratified by age group Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause LRTD hospitalizations stratified by age group
Cohort Secondary 10: VEs calculated as 1 minus the HR comparing the incidence of all-cause death among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100%. Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause death
Cohort Secondary 3: VE calculated as 1 minus the hazard ratio (HR) comparing the incidence of severe all-cause LRTD among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100%. Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against severe all-cause LRTD.
Cohort Secondary 4: ABRYSVO all-cause VE estimates stratified by chronic medical condition risk category. Adjusted for confounding factors using Cox proportional hazard regression. Up to 2 years To estimate the effectiveness of ABRYSVO against all-cause LRTD hospitalizations, stratified by chronic medical condition risk category (3 strata: not high-risk conditions, immunocompromising high-risk conditions, non-immunocompromising high-risk conditions)
Cohort Secondary 5: VE calculated as 1 minus the HR comparing the incidence of all-cause LRTD among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100%. Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause LRTD separately for: outpatient visits (without subsequent hospitalization or ED visit within 14 days) and ED events (ED without subsequent hospitalization)
Cohort Secondary 6: VE calculated as 1 minus the HR comparing the incidence of all-cause ARI among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100%. Up to 2 years To estimate the effectiveness of ABRYSVO against all-cause ARI separately for: hospitalizations and ED events (without subsequent hospitalizations)
Cohort Secondary 7: VEs calculated as 1 minus the HR comparing the incidence of all-cause respiratory, cardiac, cardiorespiratory, CHF and COPD hospitalizations among patients vaccinated with ABRYSVO versus those not vaccinated, multiplied by 100%. Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause respiratory, circulatory, cardio-respiratory, cardiac, and CHF and COPD hospitalizations
Cohort Secondary 8: Rate reduction calculated as the rate difference of all-cause ARI/LRTD hospitalizations/outpatient/ED events among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO. Up to 2 years To estimate the absolute rate reductions in all-cause ARI/LRTD hospitalizations/outpatient/ED events by vaccination status at defined timepoints, and by important demographic and clinical characteristics
Cohort Secondary 4: ABRYSVO all-cause VE estimates stratified by age groups. Adjusted for confounding factors using Cox proportional hazard regression. Up to 2 years To estimate the effectiveness of ABRYSVO against all-cause LRTD hospitalizations, stratified by age
Cohort Secondary 5: ABRYSVO all-cause VE estimates stratified by frailty index. Adjusted for confounding factors using Cox proportional hazard regression. Up to 2 years To estimate the effectiveness of ABRYSVO against all-cause LRTD hospitalization stratified by frailty index
Cohort Secondary 11: VEs calculated as 1 minus the HR comparing the incidence of all-cause hospitalizations among patients vaccinated with ABRYSVO versus those not vaccinated with ABRYSVO, multiplied by 100% Up to 2 years Adjusted for confounding factors using Cox proportional hazard regression. To estimate the effectiveness of ABRYSVO against all-cause hospitalization
SSA Primary: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO® for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, using LRTD events from the 3rd season Up to 3 years Among those with 3 completed RSV seasons after vaccination with a single dose ABRYSVO®, to estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations during the 3rd RSV season after a single dose
SSA Secondary 1: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO® for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, using LRTD events from the 2nd season Up to 3 years Among those with 2 completed RSV seasons after vaccination with a single dose ABRYSVO®, to estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations during 2nd RSV season after a single dose
SSA Secondary 2: VE calculated as 1 minus the OR comparing the odds of being vaccinated with ABRYSVO® for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, using LRTD events from the 4th season Up to 3 years Among those with 4 completed RSV seasons after vaccination with a single dose ABRYSVO®, to estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations during 4th RSV season after a single dose
SSA Secondary 4: After the 2nd RSV season, VE calculated as 1 minus the OR comparing the odds of ABRYSVO® vaccination and timing compared with unvaccinated, stratified by time since vaccination, multiplied by 100%, using LRTD events from the 2nd season Up to 3 years To estimate effectiveness of ABRYSVO® in the second season after a single dose by time since vaccination, defined in 3-month intervals up to 24 months
SSA Secondary 5: After the 3rd RSV season, VE calculated as 1 minus the OR comparing the odds of ABRYSVO® vaccination and timing compared with unvaccinated, stratified by time since vaccination, multiplied by 100%, using LRTD events from the 3rd season Up to 3 years To estimate effectiveness of ABRYSVO® in the third season after a single dose by time since vaccination, defined in 3-month intervals up to 36 months
SSA Secondary 6: After the 4th RSV season, VE calculated as 1 minus the OR comparing the odds of ABRYSVO® vaccination and timing compared with unvaccinated, stratified by time since vaccination, multiplied by 100%, using LRTD events from the 4th season Up to 3 years To estimate effectiveness of ABRYSVO® in the fourth season after a single dose by time since vaccination, defined in 3-month intervals up to 48 months
SSA Secondary 7: After the 5th RSV season, VE calculated as 1 minus the OR comparing the odds of ABRYSVO® vaccination and timing compared with unvaccinated, stratified by time since vaccination, multiplied by 100%, using LRTD events from the 5th season Up to 3 years To estimate effectiveness of ABRYSVO® in the fifth season after a single dose by time since vaccination, defined in 3-month intervals up to 60 months
SSB Primary: VE calculated as 1 minus OR comparing odds of being vaccinated w 2 doses of ABRYSVO vs not vaccinated with any ABRYSVO for RSV-related hospitalized LRTD cases and controls, multiplied by 100%, using events from 1st season after 2nd dose Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations after revaccination among those with 2 vs 0 dose of ABRYSVO, in the first season after revaccination (pending ACIP recommendation for revaccination)
SSB Secondary 1: VE calculated as 1 minus OR comparing odds of vaccinated w 2 doses of ABRYSVO vs vaccinated with 1 dose of ABRYSVO for RSV-related hospitalized LRTD cases and controls, x 100%, using events from 1st season after 1st and 2nd dose Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations after revaccination among those with 2 vs 1 dose of ABRYSVO, in the first season after revaccination (pending ACIP recommendation for revaccination)
SSB Secondary 2: VE calculated as 1 minus OR comparing odds of vaccinated w 2 doses of ABRYSVO vs not vaccinated with any ABRYSVO for RSV-related hospitalized LRTD cases and controls, x 100%*, using events from the 2nd season after the 1st and 2nd dose Up to 2 years To estimate the effectiveness of ABRYSVO® against RSV-related LRTD hospitalizations after revaccination among those with 2 vs 0 dose of ABRYSVO®, in the second season after revaccination (pending ACIP recommendation for revaccination)
SSB Secondary 3: VE calculated as 1 minus OR comparing odds of vaccinated with 2 doses of ABRYSVO vs vaccinated w 1 dose of ABRYSVO for RSV-related hospitalized LRTD cases and controls, x 100%, using events from 2nd season after 1st and 2nd dose Up to 2 years To estimate the effectiveness of ABRYSVO against RSV-related LRTD hospitalizations after revaccination among those with 2 vs 1 dose of ABRYSVO, in the second season after revaccination (pending ACIP recommendation for revaccination)
Trial Locations
- Locations (1)
Pfizer
🇺🇸New York, New York, United States