A Study to Learn About How 20-Valent Pneumococcal Conjugate Vaccine Works in a Real-world Setting

Study Overview
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Brief Summary
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The purpose of this study is to learn about how well the 20-valent pneumococcal conjugate vaccine (20vPnC) works against radiologically-confirmed community- acquired pneumonia (RAD+CAP) . This study is seeking participants who: are male or female ≥65 years of age. are hospitalized with physician suspicion of community acquired pneumonia (CAP). Participants will be asked to provide demographic and medical history information, and to provide a urine sample that will be used to test for pneumonia. We will compare how many participants have pneumonia and were previously vaccinated with 20vPnC with how many participants who have pneumonia and have not been vaccinated with 20vPnC. Participants will actively take part in the study for about 1-2 days. Information on participant's illness and hospitalization details will be collected through day 30 of their hospitalization through medical chart review.

Detailed Description
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This is an observational test-negative design study in which all study participants are adults ≥65 years of age hospitalized with RAD+CAP at one of the study sites. The only protocol-specified study procedure is a non-invasive urine specimen collection for pneumococcal detection using BinaxNOW® S. pneumoniae and the serotype-specific urinary antigen detection (UAD) assays. Cases and controls will be differentiated by the presence of vaccine serotypes that are identified by any method, including Quellung reaction of pneumococcal isolates obtained from standard of care (SOC) cultures from blood or high-quality respiratory tract specimens, or serotype specific UAD assays performed on urine specimens. The serotype-specific UAD assays, termed UAD-1 and UAD-2, detect the 13 serotypes in 13vPnC (1, 3, 4, 5, 6A/C, 6B/D, 7F/A, 9V/A, 14, 18C/A/ B/ F, 19A, 19F, 23F) (UAD-1) and 11 additional serotypes (2, 8, 9N, 10A/39, 11A/D/F, 12F, 15B/C, 17F/A, 20A/B, 22F/A, 33F/A) (UAD-2). For the primary objective, cases will be defined as participants hospitalized for RAD+CAP in whom the 7 additional serotypes in 20vPnC beyond 13vPnC plus 15C are identified. All other participants who meet study inclusion criteria but for whom 20vPnC serotypes are not identified from any source and all other RAD+CAP of non-pneumococcal etiologies will serve as test-negative controls.

Official Title
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A Phase 4 Study Using a Test-Negative Design to Evaluate the Effectiveness of a 20-valent Pneumococcal Conjugate Vaccine Against Vaccine-type Radiologically-confirmed Community-acquired Pneumonia in Adults >/= 65 Years of Age

Conditions
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Pneumonia

Intervention / Treatment
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* Diagnostic Test: Diagnostic test on urine samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥65 years of age. Hospitalized participant with physician clinical suspicion of CAP with the presence of ≥2 of the following 10 clinical signs or symptoms: fever (oral temperature >38.0°C/100.4°F or tympanic temperature >38.5°C/101.2°F), hypothermia (<35.5°C/95.9°F measured by a healthcare provider) chills or rigors, pleuritic chest pain, new or worsening cough, sputum production, dyspnea (shortness of breath), tachypnea (respiratory rate >20/min), malaise, or abnormal auscultatory findings suggestive of pneumonia (rales or evidence of pulmonary consolidation including dullness on percussion, bronchial breath sounds, or egophony). Has a radiographic finding that is consistent with pneumonia (e.g., pleural effusion, increased pulmonary density due to infection, the presence of alveolar infiltrates [multi-lobar, lobar, or segmental] containing air bronchograms). Capable of giving signed informed consent Exclusion Criteria: Any participant who develops signs and symptoms of pneumonia after being hospitalized for ≥48 hours (either at the study site, another transferring hospital, or a combination of these). Received any pneumococcal vaccine ≤30 days prior to enrollment. Unable to provide urine specimen (e.g. anuric). Previous enrollment in the study within the past 30 days.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>Cases will be defined as participants hospitalized for RAD+CAP in whom the 7 additional serotypes in 20vPnC beyond 13vPnC plus 15C. | Diagnostic Test: Diagnostic test on urine samples<br>* Testing by BinaxNOW® S. pneumoniae and serotype-specific urine antigen detection (UAD) assays (UAD-1 and UAD-2).<br>|
| Control<br>All other participants who meet study inclusion criteria but for whom 20vPnC serotypes are not identified from any source and all other RAD+CAP of non-pneumococcal etiologies will serve as test-negative controls. | Diagnostic Test: Diagnostic test on urine samples<br>* Testing by BinaxNOW® S. pneumoniae and serotype-specific urine antigen detection (UAD) assays (UAD-1 and UAD-2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine effectiveness calculated as 1 minus the odds ratio for 20vPnC vaccination among cases vs. controls multiplied by 100 adjusted for potentially confounding variables. |  | 55 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine effectiveness calculated as 1 minus the odds ratio for 20vPnC vaccination among cases and controls multiplied by 100 adjusted for potentially confounding variables. |  | 55 months | 
| The proportion of participants with RAD+CAP who are positive for any of the 7 additional serotypes contained in 20vPnC beyond 13vPnC plus 15C as detected by UAD-2 or culture. |  | 55 months | 
| The proportion of participants with RAD+CAP who are positive for any of the serotypes contained in 20vPnC plus 6C and 15C as detected by UAD-1, UAD-2, or culture |  | 55 months | 
| The proportion of participants with RAD+CAP who are positive for any of the serotypes contained in 13vPnC plus 6C as detected by either UAD-1 or culture. |  | 55 months | 
| Among those positive for a serotype detected by serotype-specific UAD, the proportion of participants with RAD+CAP who are positive for any of the UAD serotypes as detected by UAD-1, UAD-2, or culture. |  | 55 months | 
| The proportion of participants with RAD+CAP who have S. pneumoniae identified by culture, BinaxNOW®, or serotype-specific UADs. |  | 55 months | 
| Clinical characteristics of disease and hospitalization among those with any RAD+CAP due to all 13vPnC and/or 20vPnC serotypes plus 6C and 15C individually and aggregately. |  | 55 months |