Clinical trial NCT06077968: A Study to Learn About ABRYSVO Vaccine in Older Adults to Prevent Severe Respiratory Syncytial Virus (RSV) Disease
Official title: Retrospective Study Evaluating ABRYSVO Vaccine Effectiveness Against Severe Lower Respiratory Tract Infection in Older Adults
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Respiratory Syncytial Viruses
Keywords: Lower respiratory tract infections
Acute respiratory infections
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Kaiser Permanente
First posted: 2023-10-11
Enrollment: 1
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a retrospective database study using existing healthcare data, no patients will be actively enrolled.

TND: All KPSC patients will be included who are: 1) eligible for ABRYSVO vaccination per ACIP 2) admitted to the hospital or seen in the ED with an LRTD diagnosis and 3) RSV tested either through standard of care testing (SOC) or blinded testing of remnant SOC respiratory specimens (NP swabs, other) in a centralized lab using a multiplex RT-PCR respiratory panel assay, 4) presenting after start of the study period. Specimens will be de-identified and tested keeping linkage to clinical data.

Cohort: The cohort study will include all KPSC members eligible for vaccination as of the start of the study period (depending on the KPSC vaccination start date and rate of vaccine uptake).

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.

Eligibility criteria: Inclusion Criteria:

Test Negative Design:

1. 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.
2. 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.
3. 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.
4. 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:

1. All KPSC members eligible to receive ABRYSVO as of start of study period.
2. 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.

Exclusion Criteria:

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.

Primary outcomes:
measure: 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%.
timeFrame: Up to 2 years
Secondary outcomes:
measure: 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.
timeFrame: Up to 2 years
measure: TND Secondary 2: ABRYSVO VE estimates stratified by age groups. Adjusted for confounding factors using logistic regression.
timeFrame: Up to 2 years
measure: TND Secondary 3: ABRYSVO VE estimates stratified by virus subgroups. Adjusted for confounding factors using logistic regression.
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: TND Secondary 5: ABRYSVO VE estimates stratified by frailty index. Adjusted for confounding factors using logistic regression.
timeFrame: Up to 2 years
measure: TND Secondary 6: ABRYSVO VE estimates stratified by chronic medical condition risk category. Adjusted for confounding factors using logistic regression.
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
measure: TND Secondary 12: ABRYSVO® RSV-related VE estimates stratified by age group and chronic medical risk categories
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: Cohort Secondary 2: ABRYSVO® all-cause VE estimates stratified by age group
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: Cohort Secondary 4: ABRYSVO all-cause VE estimates stratified by chronic medical condition risk category. Adjusted for confounding factors using Cox proportional hazard regression.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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.
timeFrame: Up to 2 years
measure: Cohort Secondary 4: ABRYSVO all-cause VE estimates stratified by age groups. Adjusted for confounding factors using Cox proportional hazard regression.
timeFrame: Up to 2 years
measure: Cohort Secondary 5: ABRYSVO all-cause VE estimates stratified by frailty index. Adjusted for confounding factors using Cox proportional hazard regression.
timeFrame: Up to 2 years
measure: 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%.
timeFrame: Up to 2 years
measure: 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%
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
measure: 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
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Pfizer
state: New York
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: