Clinical trial NCT05688774: Study of Progression of Community Acquired Pneumonia in the Hospital in Patients With More Severe Preexisting Diseases and Immunosuppression
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pneumonia
Sepsis
Shock, Septic
Keywords: community ascquired pneumonia
CAP
disease progression
Lead sponsor: Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
name: University of Leipzig
name: Jena University Hospital
First posted: 2023-01-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients hospitalized for treatment of community acquired pneumonia. Patients can be enrolled in general care, intensive care, and in emergency departments.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Worst measure of disease severity
timeFrame: Between enrollment and day six
Secondary outcomes:
measure: All cause mortality
timeFrame: up to one year after enrollment
measure: disease-specific mortality
timeFrame: up to one year after enrollment
measure: duration of hospitalization
timeFrame: up to one year after enrollment
measure: duration of intensive care treatment
timeFrame: up to one year after enrollment
measure: duration of ventilator assisted breathing
timeFrame: up to one year after enrollment
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Infektiologie und Pneumologie
city: Berlin
country: Germany
facility: Humboldt-Klinikum Vivantes, Kardiologie und kons. Intensivmedizin
city: Berlin
country: Germany
facility: Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau, Innere Medizin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg, Klinik für Pneumologie und Anästhesie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Kardiologie 1
city: Rotenburg
country: Germany
facility: Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie
Study officials:
affiliation: Charité Univerity, Berlin, Germany
name: Norbert Suttorp, MD
role: PRINCIPAL_INVESTIGATOR
References: