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

Official title

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

Overview

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) due to the 7 new serotypes (types of a bacteria called Streptococcus pneumoniae that cause pneumonia) included in 20vPnC vaccine. This study is seeking participants who: * are male or female ≥65 years of age. * are hospitalized with physician suspicion of community acquired pneumonia (CAP). * have pneumonia confirmed with imaging like a chest x-ray 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 caused by specific strains of a bacteria called Streptococcus pneumoniae. We will compare the proportion of participants who have pneumonia caused by specific strains of the bacteria Streptococcus pneumoniae and were previously vaccinated with 20vPnC with the proportion of participants who have pneumonia caused by something other than vaccine type Streptococcus pneumoniae and have 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

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.

Interventions

• Diagnostic test Diagnostic test on urine samples
  Testing by BinaxNOW® S. pneumoniae and serotype-specific urine antigen detection (UAD) assays (UAD-1 and UAD-2).

Primary outcome measures

• Effectiveness of 20vPnC against all (invasive + non-invasive) RAD+CAP due to the 7 additional serotypes in 20vPnC beyond 13vPnC plus 15C [Time frame: 55 months]

Secondary outcome measures (12)

• Effectiveness of 20vPnC against non-invasive RAD+CAP due to the 7 additional serotypes in 20vPnC beyond 13vPnC plus 15C [Time frame: 55 months]
• Effectiveness of 20vPnC against all RAD+CAP due to any 20vPnC serotype plus 6C and 15C [Time frame: 55 months]
• Effectiveness of 20vPnC against non-invasive RAD+CAP due to any 20vPnC serotype plus 6C and 15C [Time frame: 55 months]
• Proportion of participants with RAD+CAP due to the 7 additional serotypes in 20vPnC beyond 13vPnC plus 15C, individually and aggregately [Time frame: 55 months]
• The proportion of all RAD+CAP due to any 20vPnC serotype plus 6C and 15C, individually and aggregately [Time frame: 55 months]
• The proportion of all RAD+CAP due to any 13vPnC serotype plus 6C, individually and aggregately [Time frame: 55 months]
• Among those positive for a serotype detected by serotype-specific UAD, the proportion of participants with any RAD+CAP due to each UAD serotype individually and aggregately [Time frame: 55 months]
• The proportion of participants with any RAD+CAP due to S. pneumoniae [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 55 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study locations

United States · 40 centers

• El Centro Regional Medical Center — El Centro
• Kaiser Permanente Fontana Medical Center — Fontana
• Kaiser Permanente West Los Angeles Medical Center — Los Angeles
• Kaiser Permanente Vaccine Study Center — Oakland
• Kaiser Permanente Oakland Medical Center — Oakland
• Kaiser Permanente Ontario Medical Center — Ontario
• Southern California Permanente Medical Group (SCPMG) — Pasadena
• Kaiser Permanente Riverside Medical Center — Riverside
• … and 32 more centers

Spain · 10 centers

• Hospital Universitari de Bellvitge — L'Hospitalet de Llobregat
• Hospital Universitarios De Getafe — Getafe
• Hospital Universitario Severo Ochoa — Leganés
• CHUVI- Hospital Alvaro Cunqueiro — Vigo
• Hospital Universitari i Politecnic La Fe — Valencia
• Hospital Universitari Vall D´Hebron — Barcelona
• Hospital Universitario Clinico San Carlos — Madrid
• Hospital Universitario La Paz — Madrid
• … and 2 more centers

Israel · 4 centers

• Emek Medical Center — Afula
• Soroka University Medical Center — Beersheba
• Meir Medical Center — Kfar Saba
• Infectious Diseases Unit Tel-Aviv Sourasky Medical Center — Tel Aviv

Identifiers

NCT: NCT05452941 · B7471015 · 2023-507293-40-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗