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

Sepsis Clinical Trial

— PROGRESSCOMORB  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05688774
• Other study ID #: PROGRESS-COMORB
• Status: Recruiting
• Start date: February 28, 2022
• Est. completion date: February 28, 2028

Study information

• Verified date: March 2024
• Source: Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps
• Contact: Sarah Berger, MD
• Phone: +49-30-450553347
• Email: sarah.berger[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 28, 2028
• Est. primary completion date: February 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Hospitalization with community acquired pneumonia (CAP) confirmed by pulmonary infiltrate in chest imaging

2. Valid informed consent form

3. Working diagnosis of CAP by enrolling physician

4. No hospitalization for any reason within 28 days prior to hospitalization for the current episode of CAP

5. 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

6. 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

• Heart failure: New York Heart Association (NYHA) Stadium IV or HFrEF (defined as left ventricular ejection fraction <40%).

• Decompensated liver disease (Child-Pugh class C)

• Diabetes mellitus with HbA1c = 8,5 %

• End-stage renal disease requiring dialysis

• Pulmonary hypertension (all classes) with mPAP > 20 mmHg (right heart catheter)

Exclusion Criteria:

1. Participation in this study at an earlier time

2. More than 48 hours in the hospital before enrollment (for patients directly to intensive care: more than 7 days)

3. Pregnancy

4. Breastfeeding

5. Active tuberculosis

6. Acute lung injury or acute respiratory distress syndrome for extrapulmonary reasons

7. Massive aspiration

8. Sepsis with extrapulmonary focus

9. Acute pulmonary embolism

Related Conditions & MeSH terms

• Disease Progression
• Pneumonia
• Sepsis
• Shock, Septic

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Infektiologie und Pneumologie	Berlin
Germany	Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie	Berlin
Germany	Humboldt-Klinikum Vivantes, Kardiologie und kons. Intensivmedizin	Berlin
Germany	Städtisches Klinikum Dessau, Innere Medizin	Dessau
Germany	Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale	Hamburg
Germany	Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie	Leipzig
Germany	Universitätsklinikum Leipzig, Klinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie	Leipzig
Germany	Universitätsklinikum Gießen und Marburg, Klinik für Pneumologie und Anästhesie	Marburg
Germany	Universitätsklinikum Münster, Kardiologie 1	Münster
Germany	Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie	Rotenburg

Sponsors (4)

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

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Worst measure of disease severity	Disease severity is operationalized by the Sequential Organ Failure Assessment (SOFA-score).	Between enrollment and day six
Secondary	All cause mortality		up to one year after enrollment
Secondary	disease-specific mortality		up to one year after enrollment
Secondary	duration of hospitalization		up to one year after enrollment
Secondary	duration of intensive care treatment		up to one year after enrollment
Secondary	duration of ventilator assisted breathing		up to one year after enrollment