Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03908632
Recruitment Status : Recruiting
First Posted : April 9, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is an observational study in 1,000 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 14 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 14 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.

Condition or disease
Coccidioidomycosis Pneumonia

Detailed Description:
This is an observational study in 1,000 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 14 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 14 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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: 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)
Actual Study Start Date : February 15, 2019
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Group/Cohort
Step 1
Subjects 14 years or older diagnosed with Community Acquired Pneumonia (CAP) and positive serology for primary pulmonary coccidioidomycosis (PPC) will enroll in Step 1 within 14 days of symptom onset, n=1000
Step 2
Subjects with a diagnosis of primary pulmonary coccidioidomycosis (PPC) confirmed by positive serologic testing during Step 1 will enter Step 2 within 14 days of their test collection date, n=200



Primary Outcome Measures :
  1. Proportion of subjects with primary pulmonary coccidioidomycosis (PPC) among subjects with Community Acquired Pneumonia CAP) in Step 1 [ Time Frame: Day 1 through Day 22 ]

Secondary Outcome Measures :
  1. Associations between chest radiograph and antifungal treatment for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  2. Associations between Observational Study to Assess the Prevalence and Outcomes of Primary Pulmonary Coccidioidomycosis (SAnds-PPC) and antifungal treatment for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  3. Associations between severity and antifungal treatment for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  4. Compare change in chest radiograph findings score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  5. Compare disease severity score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  6. Compare mortality rates for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  7. Compare percent of subjects that develop persistent or disseminated PPC for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 85 through Day 730 ]
  8. Compare SAnds-PPC score for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 1 through Day 730 ]
  9. Compare time missed from school and work for subjects that are prescribed antifungal therapy vs. no therapy for PPC, Step 2 [ Time Frame: Day 1 through Day 180 ]
  10. Descriptive statistics of subjects' demographics in Step 1 [ Time Frame: Day 1 ]
  11. Descriptive statistics of subjects' Erythrocyte Sedimentation Rate (ESR) in Step 1 [ Time Frame: Day 1 ]
  12. Descriptive statistics of subjects' High sensitivity C-reactive protein (hsCRP) in Step 1 [ Time Frame: Day 1 ]
  13. Descriptive statistics of subjects' Observational Study to Assess the Prevalence and Outcomes of Primary Pulmonary Coccidioidomycosis (SAnds-PPC) in Step 1 [ Time Frame: Day 1 ]
  14. Descriptive statistics of subjects' procalcitonin in Step 1 [ Time Frame: Day 1 ]
  15. Descriptive statistics of subjects' serologic titers in Step 1 [ Time Frame: Day 1 ]
  16. Frequency of prescription of antifungal therapy prescribed for Community Acquired Pneumonia (CAP) for Step 1 [ Time Frame: Day 1 through Day 22 ]
  17. Frequency of prescription of antifungal therapy prescribed for primary pulmonary coccidioidomycosis (PPC) for Step 2 [ Time Frame: Day 1 through Day 730 ]
  18. Mean of change in chest radiograph findings score as a part of standard of care, Step 2 [ Time Frame: From 4 to 8 weeks after Initial chest x-ray date ]
  19. Mean of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  20. Mean of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  21. Mean of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  22. Mean of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  23. Mean of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  24. Median of change in chest radiograph findings score as a part of standard of care, Step 2 [ Time Frame: From 4 to 8 weeks after Initial chest x-ray date ]
  25. Median of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  26. Median of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  27. Median of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  28. Median of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  29. Median of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  30. Quartiles of change in chest radiograph findings score as a part of standard of care, Step 2 [ Time Frame: From 4 to 8 weeks after Initial chest x-ray date ]
  31. Quartiles of disease severity score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  32. Quartiles of the disease severity score for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  33. Quartiles of the modified SAnds-PPC score (clinical scoring system) for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  34. Quartiles of the SAnds-PPC score (clinical scoring system) for subjects with persistent or disseminated primary pulmonary coccidioidomycosis (PPC), Step 2 [ Time Frame: Day 180 through Day 730 ]
  35. Quartiles of time to resolution of each symptom contributing to the modified SAnds-PPC score for subjects with primary pulmonary coccidioidomycosis (PPC) from Step 2 [ Time Frame: Day 1 through Day 85 ]
  36. 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 2 [ Time Frame: Day 1 through Day 730 ]
  37. 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 2 [ Time Frame: Day 1 through Day 730 ]

Biospecimen Retention:   Samples With DNA
Venous blood samples (approximately 10 mL) to determine Coccidioides antibodies for entry will be performed locally at the sites for Step 1 Day 1, and if negative this will be repeated at Day 22. Erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), and procalcitonin will be measured on Step 1 Day 1, or if enrolled directly into Step 2, at Step 2 Day 1. Total blood volume for subjects participating only in Step 1 will be up to 65 ml (95 mL for subjects consenting to additional sample collection for future use). Total blood volume collected per participant who participates in Step 1 and Step 2 is up to 95 mL (up to 155 mL for subjects consenting to additional sample collection for future use). Volumes may be higher for subjects with additional clinic visits after Step 2 Visit 06 due to persistent or disseminated disease.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   14 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Step 1 will include at least 1,000 persons aged 14 and older diagnosed with community acquired pneumonia (CAP) in coccidioidomycosis endemic areas. Step 2 will involve at least 200 persons aged 14 and older with primary pulmonary coccidioidomycosis.
Criteria

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 14 d 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.**
  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.

    • 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.

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 14 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 14 days inclusive prior to enrollment is permissible.

  2. Presence of cavitary lung disease.
  3. Evidence of disseminated, extrathoracic disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03908632


Contacts
Layout table for location contacts
Contact: Emmanuel Walter 19196205350 walte002@mc.duke.edu

Locations
Layout table for location information
United States, Arizona
Banner - University Medical Center Advanced Lung Disease Clinic - Phoenix Recruiting
Phoenix, Arizona, United States, 85006
The University of Arizona - Banner University Medical Center Tucson Campus - Tucson Recruiting
Tucson, Arizona, United States, 85724-0001
United States, California
Kaiser Permanente Chester Avenue Medical Offices - Pulmonology Recruiting
Bakersfield, California, United States, 93301
Kern Medical Center Recruiting
Bakersfield, California, United States, 93306-4018
UCSF Fresno Center for Medical Education and Research - Clinical Research Center Recruiting
Fresno, California, United States, 93701
Kaiser Permanente Antelope Valley Medical Offices - Infectious Diseases Recruiting
Lancaster, California, United States, 93534
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03908632     History of Changes
Other Study ID Numbers: 14-1053
HHSN272201300017I
First Posted: April 9, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: March 27, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Community Acquired Pneumonia
Endemic Areas
Observational Study
Primary Pulmonary Coccidioidomycosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Coccidioidomycosis
Coccidiosis
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Mycoses
Protozoan Infections
Parasitic Diseases