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An Observational Study to Assess the Prevalence and Outcomes of Primary Pulmonary Coccidioidomycosis in Persons Aged > / = 14 Years Presenting With Community Acquired Pneumonia (CAP) in Endemic Areas (SAnds-PPC)

Completed
Conditions
Coccidioidomycosis
Pneumonia
Registration Number
NCT03908632
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

This is an observational study in 750 individuals aged 14 years or older, diagnosed with Community Acquired Pneumonia (CAP) who meet all eligibility criteria in Coccidioides endemic regions. This study is designed to provide data on the prevalence of primary pulmonary coccidioidomycosis among persons presenting with CAP in endemic regions. Among individuals diagnosed with primary pulmonary coccidioidomycosis, we aim to describe the clinical course, predictors of the clinical course and compare the response to prescribed antifungal therapy versus no antifungal therapy. The hypothesis for patients with primary pulmonary coccidioidomycosis is that early treatment with antifungal therapy is effective in reducing the frequency, severity and associated adverse outcomes of infection with recently acquired coccidioidomycosis pneumonia. The study will be divided into Step 1 and Step 2. Step 1 will identify which subjects have primary pulmonary coccidioidomycosis based on the case definition for the protocol and Step 2 will follow subjects who meet the case definition and will observe their clinical management and clinical outcomes. Subjects will enroll in Step 1 within 28 days of symptom onset. In Step 1, blood work for serologic determination of Coccidioides infection will be drawn at the time of enrollment (Day 1), and again 21 days later if a positive result is not reported at Day 1. Subjects with a diagnosis of primary pulmonary coccidioidomycosis confirmed by positive serologic testing during Step 1 will enter Step 2 within 21 days of a positive test result; subjects with a negative serology at Day 1 and Day 22 will not be followed further. Subjects referred to the study after a diagnosis of primary pulmonary coccidioidomycosis confirmed by positive serologic testing will also be allowed to enter Step 2 directly within 21 days of a positive test result and within 7 weeks of symptom onset, as long as they meet study enrollment criteria. The primary objective is to assess the prevalence of primary pulmonary coccidioidomycosis (PPC) in subjects with community acquired pneumonia (CAP) in coccidioidomycosis endemic areas.

Detailed Description

This is an observational study in 750 individuals aged 14 years or older, diagnosed with Community Acquired Pneumonia (CAP) who meet all eligibility criteria in Coccidioides endemic regions. This study is designed to provide data on the prevalence of primary pulmonary coccidioidomycosis among persons presenting with CAP in endemic regions. Among individuals diagnosed with primary pulmonary coccidioidomycosis, we aim to describe the clinical course, predictors of the clinical course and compare the response to prescribed antifungal therapy versus no antifungal therapy. The hypothesis for patients with primary pulmonary coccidioidomycosis is that early treatment with antifungal therapy is effective in reducing the frequency, severity and associated adverse outcomes of infection with recently acquired coccidioidomycosis pneumonia. The study will be divided into Step 1 and Step 2. Step 1 will identify which subjects have primary pulmonary coccidioidomycosis based on the case definition for the protocol and Step 2 will follow subjects who meet the case definition and will observe their clinical management and clinical outcomes. Subjects will enroll in Step 1 within 28 days of symptom onset. In Step 1, blood work for serologic determination of Coccidioides infection will be drawn at the time of enrollment (Day 1), and again 21 days later if a positive result is not reported at Day 1. Subjects with a diagnosis of primary pulmonary coccidioidomycosis confirmed by positive serologic testing during Step 1 will enter Step 2 within 21 days of a positive test result; subjects with a negative serology at Day 1 and Day 22 will not be followed further. Subjects referred to the study after a diagnosis of primary pulmonary coccidioidomycosis confirmed by positive serologic testing will also be allowed to enter Step 2 directly within 21 days of a positive test result and within 7 weeks of symptom onset, as long as they meet study enrollment criteria. The primary objective is to assess the prevalence of primary pulmonary coccidioidomycosis (PPC) in subjects with community acquired pneumonia (CAP) in coccidioidomycosis endemic areas. The secondary objectives are divided into two categories. For subjects with CAP in coccidioidomycosis endemic areas the secondary objectives are: 1) To determine demographic, clinical and laboratory factors that predict PPC; 2) To describe the practice of empiric antifungal treatment of subjects with CAP. For subjects with confirmed primary pulmonary coccidioidomycosis the secondary objectives are: 1) To describe the clinical course of primary pulmonary coccidioidomycosis from earliest presentation; 2) To assess the demographic, clinical, laboratory and treatment predictors of the clinical course of primary pulmonary coccidioidomycosis; 3) To describe the practice of antifungal treatment of subjects with confirmed primary pulmonary coccidioidomycosis; 4) To compare the outcomes of antifungal therapy vs. no therapy for primary pulmonary coccidioidomycosis as measured by clinical signs and symptoms, functional scores of health and well-being and ability to participate in social roles and activities, time missed from school and work, dissemination, and mortality.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
651
Inclusion Criteria

Step 1 Subject Inclusion Criteria:

  1. Aged > / = 14 years and presenting for clinical care in coccidioidomycosis endemic areas.

  2. Diagnosis of community acquired pneumonia (CAP) established by a health care provider.

  3. Pulmonary opacity on chest X-ray or computerized tomography (CT) scan consistent with CAP.

  4. Onset of symptoms related to current CAP diagnosis within 28 days prior to enrollment.

  5. Must be able to understand the study and provide informed consent.*

    *If aged < 18 years, the parent(s) or guardian must be able to understand the study and provide informed consent, with the assent of the minor.

  6. Willing and able to comply with study procedures and complete study visits.

  7. Willing to allow access to medical records, and medical records are available to the study team.

Step 2 Subject Inclusion Criteria:

  1. Aged > / = 14 years

  2. Presence of at least one influenza-like sign or symptom (e.g. fever, chest pain, cough, myalgia, arthralgia, and headache.

  3. Onset of any symptoms no earlier than 7 weeks prior to enrollment into Step 2.

  4. Opacity/pleural effusion diagnosed by chest radiograph or computerized tomography (CT) scan .

  5. Positive result for any serologic test confirming coccidioidomycosis obtained within 21 days prior to enrollment into Step 2.*

    * The assays considered for this criterion are: coccidioidal immunoglobulin M (IgM) by immunodiffusion, enzyme immunoassay (EIA), latex agglutination or tube precipitin OR coccidioidal immunoglobulin G (IgG) by immunodiffusion, EIA, or complement fixation. The interpretation of positive or negative is per the reporting laboratory instructions

  6. Must be able to understand the study and provide informed consent.**

    **If aged <18 years, the parent(s) or guardian must be able to understand the study and provide informed consent, with the assent of the minor.

  7. Willing and able to comply with study procedures and complete study visits.

  8. Willing to allow access to medical records, and medical records are available to the study team.

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Exclusion Criteria

Step 1 Subject Exclusion Criteria:

  1. Have documented microbiologically- or serologically-confirmed past infections with Coccidioides.*

    *An initial positive serologic test obtained within 21 days inclusive prior to enrollment is permissible.

  2. Hospitalization within 14 days prior to the onset of pneumonia symptoms.

  3. Presence of cavitary lung disease.

  4. Evidence of disseminated, extrathoracic disease.

Step 2 Subject Exclusion Criteria:

  1. Have documented microbiologically- or serologically-confirmed past infections with Coccidioides.*

    *An initial positive serologic test obtained within 21 days inclusive prior to enrollment is permissible.

  2. Presence of cavitary lung disease.

  3. Evidence of disseminated, extrathoracic disease.

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Proportion of subjects with primary pulmonary coccidioidomycosis (PPC) among subjects with Community Acquired Pneumonia CAP) in Step 1Day 1 through Day 22
Secondary Outcome Measures
NameTimeMethod
Associations between chest radiograph and antifungal treatment for PPC, Step 2Day 1 through Day 730
Associations between Observational Study to Assess the Prevalence and Outcomes of Primary Pulmonary Coccidioidomycosis (SAnds-PPC) and antifungal treatment for PPC, Step 2Day 1 through Day 730
Associations between severity and antifungal treatment for PPC, Step 2Day 1 through Day 730
Compare change in chest radiograph findings score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 730
Compare disease severity score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 365
Compare mortality rates for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 365
Compare percent of subjects that develop persistent or disseminated PPC for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 85 through Day 730
Compare SAnds-PPC score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 730
Compare time missed from school and work for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 180
Descriptive statistics of subjects' demographics in Step 1Day 1
Mean of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Descriptive statistics of subjects' Erythrocyte Sedimentation Rate (ESR) in Step 1Day 1
Descriptive statistics of subjects' High sensitivity C-reactive protein (hsCRP) in Step 1Day 1
Descriptive statistics of subjects' Observational Study to Assess the Prevalence and Outcomes of Primary Pulmonary Coccidioidomycosis (SAnds-PPC) in Step 1Day 1
Descriptive statistics of subjects' procalcitonin in Step 1Day 1
Descriptive statistics of subjects' serologic titers in Step 1Day 1
Mean of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Mean of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Frequency of prescription of antifungal therapy prescribed for Community Acquired Pneumonia (CAP) for Step 1Day 1 through Day 22
Frequency of prescription of antifungal therapy prescribed for primary pulmonary coccidioidomycosis (PPC) for Step 2Day 1 through Day 730
Mean of change in chest radiograph findings score as a part of standard of care, Step 2From 4 to 8 weeks after Initial chest x-ray date
Mean of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Mean of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Median of change in chest radiograph findings score as a part of standard of care, Step 2From 4 to 8 weeks after Initial chest x-ray date
Median of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Median of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Median of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Quartiles of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Quartiles of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Median of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Quartiles of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Quartiles of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2Day 180 through Day 365
Median of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85
Summary statistics for PROMIS Item Bank v2.0 - Ability to Participate in Social Roles and Activities - Short Form 4a for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 365
Summary statistics for the mental component summary (MCS) and the physical component summary (PCS) scores of the SF-12v2 instrument for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2Day 1 through Day 365
Quartiles of change in chest radiograph findings score as a part of standard of care, Step 2From 4 to 8 weeks after Initial chest x-ray date
Quartiles of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2Day 1 through Day 85

Trial Locations

Locations (6)

Kaiser Permanente Antelope Valley Medical Offices - Infectious Diseases

🇺🇸

Lancaster, California, United States

Kaiser Permanente Chester Avenue Medical Offices - Pulmonology

🇺🇸

Bakersfield, California, United States

Banner - University Medical Center Advanced Lung Disease Clinic - Phoenix

🇺🇸

Phoenix, Arizona, United States

Kern Medical Center

🇺🇸

Bakersfield, California, United States

UCSF Fresno Center for Medical Education and Research - Clinical Research Center

🇺🇸

Fresno, California, United States

The University of Arizona - Banner University Medical Center Tucson Campus - Tucson

🇺🇸

Tucson, Arizona, United States

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