PROGRESSCOMORB: Study of Progression of Community Acquired Pneumonia in the Hospital in Patients With More Severe Preexisting Diseases and Immunosuppression

Sponsor

Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps (Other)

Overall Status

Recruiting

CT.gov ID

NCT05688774

Collaborator

Charite University, Berlin, Germany (Other), University of Leipzig (Other), Jena University Hospital (Other)

300

Enrollment

Locations

Anticipated Duration (Months)

37.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Pneumonia is a common infectious disease of the lung, often requiring treatment in the hospital. Clinical scoring systems are available, identifying patients not requiring hospitalization. However, the course of disease of patients in the hospital remains hard to predict. While most patients will recover quickly, some will, despite appropriate treatment, develop a severe course leading to sepsis and systemic responses resulting in organ dysfunction. The PROGRESS consortium aims to identify clinical, genetic, and other molecular markers and combinations there of predicting a severe course of pneumonia in the hospital. Such predictors will, for instance, support decisions on earlier transfer of patients to intensive care and thus improving outcome. PROGRESS-COMORB aims to extend findings from the previous PROGRESS study to patients with more severe preexisting conditions and immunosuppression.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia Sepsis Shock, Septic

Detailed Description

Pneumonia is a common infectious disease of the lung, often requiring treatment in the hospital. Clinical scoring systems are available, identifying patients not requiring hospitalization. However, the course of disease of patients in the hospital remains hard to predict. While most patients recover quickly, others will, despite appropriate treatment, develop a severe course leading to sepsis and systemic responses resulting in organ dysfunction. The PROGRESS consortium aims to identify clinical, genetic and other molecular markers and combinations there of predicting a severe course of pneumonia in the hospital. Such predictors will, for instance, support decisions on earlier transfer of patients to intensive care and thus improving outcome. PROGRESS-COMORB aims to extend findings from the previous PROGRESS study to patients with more severe preexisting conditions and immunosuppression.

In this observational, longitudinal case-cohort study, patients are enrolled within 48 hours of hospitalization (within 7 days for patients directly admitted to intensive care) and patient's progress is followed in much detail for up to six days thereafter. Further data are collected until discharge from the hospital. Patients are followed up on at days 28, 180, and 360 after enrollment.

Baseline assessment comprises sociodemographic, anamnestic, family history, and life-style information. Upon enrollment, Pneumonia Severity Index (PSI) and CURB-65 are determined. For the day of enrollment, up to six subsequent study days routine laboratory and clinical observations and information on therapy are documented as well as data for determining the Sequential Organ Failure Assessment (SOFA) score, Systemic Inflammatory Response Syndrome (SIRS) status, and organ dysfunction. Starting with enrollment, up to four consecutive sets of biomaterials are collected comprising serum, plasma, and materials for extraction of RNA. Blood for extraction of DNA is collected once.

Follow up comprises vital status, housing situation, recurrence of pneumonia, stroke, myocardial infarction, occurrence of diabetes and a quality of life questionnaire.

In the PROGRESS consortium, the transition (progression) from uncomplicated community-acquired pneumonia acquired pneumonia (uCAP) to severe CAP (sCAP) to CAP with severe sepsis or septic shock or multiple organ failure (ssCAP) is investigated. Previous work of the PROGRESS consortium led to the successful identification of an operationalization for the severity of CAP and causal pathomechanistic correlations, a clinical prognosis score, the assignment of altered molecules to dysfunctions of the respiratory tract, kidneys, coagulation, cardiovascular system, and liver, and a gene expression signature for early detection of patients at risk of developing ssCAP.

For the translation of findings from the PROGRESS-CAP study into clinical applicability, their applicability to CAP patients with immunosuppression or with more severe preexisting conditions has to be confirmed.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Study of Progression of Hospitalized Community Acquired Pneumonia - Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis in Patients With More Severe Preexisting Diseases and Immunosuppression to Complement the PROGRESS CAP Cohort

Actual Study Start Date :

Feb 28, 2022

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Feb 28, 2025

Outcome Measures

Primary Outcome Measures

Worst measure of disease severity [Between enrollment and day six]
Disease severity is operationalized by the Sequential Organ Failure Assessment (SOFA-score).

Secondary Outcome Measures

All cause mortality [up to one year after enrollment]
disease-specific mortality [up to one year after enrollment]
duration of hospitalization [up to one year after enrollment]
duration of intensive care treatment [up to one year after enrollment]
duration of ventilator assisted breathing [up to one year after enrollment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Hospitalization with community acquired pneumonia (CAP) confirmed by pulmonary infiltrate in chest imaging
Valid informed consent form
Working diagnosis of CAP by enrolling physician
No hospitalization for any reason within 28 days prior to hospitalization for the current episode of CAP
At least 2 out of the five following clinical symptoms:

Fever
Cough
Purulent sputum
Shortness of breath or need for respiratory support
Crackling or rales on auscultation, dullness to percussion, or bronchial breathing

At least 1 of the following criteria

Known HIV infection or AIDS
Anti-tumor treatment within the past six months
Therapy with corticosteroids ≥ 20mg for ≥ 14 days before enrollment
Non-steroidal immunosuppressive therapy within the past six months
Cytostatic therapy within the past six months
Radiation therapy within the past six months
Bone marrow transplant received
Respiratory support at home via tracheostoma
Cystic fibrosis
Congestive heart failure New York Heart Association (NYHA) IV stadium
Liver insufficiency Child-Pugh C stadium

Exclusion Criteria:

Participation in this study at an earlier time
More than 48 hours in the hospital before enrollment (for patients directly to intensive care: more than 7 days)
Pregnancy
Breastfeeding
Post-stenotic pneumonia in conjunction with bronchial carcinoma
Active tuberculosis
Acute lung injury or acute respiratory distress syndrome for extrapulmonary reasons
Massive aspiration
Sepsis with extrapulmonary focus
Acute pulmonary embolism

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Infektiologie und Pneumologie	Berlin	Germany	13353
2	Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie	Berlin	Germany	14089
3	Städtisches Klinikum Dessau, Innere Medizin	Dessau	Germany	06847
4	Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale	Hamburg	Germany	20246
5	Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie	Leipzig	Germany	04129
6	Universitätsklinikum Gießen und Marburg, Klinik für Pneumologie und Anästhesie	Marburg	Germany	35043
7	Universitätsklinikum Münster, Kardiologie 1	Münster	Germany	48149
8	Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie	Rotenburg	Germany	27356

Sponsors and Collaborators

Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps
Charite University, Berlin, Germany
University of Leipzig
Jena University Hospital