Study of Progression of Community Acquired Pneumonia in the Hospital

Completed

• Conditions: Pneumonia; Shock, Septic; Sepsis

• Registration Number: NCT02782013
• Lead Sponsor: Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps

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 study aims to identify clinical, genetic, and other molecular markers and combinations thereof 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.

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 will recover quickly, some will, despite appropriate treatment, develop a severe course leading to sepsis and systemic responses resulting in organ dysfunction. The PROGRESS study aims to identify clinical, genetic and other molecular markers and combinations thereof 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.

The PROGRESS study was initially approved by the ethics board of the University Hospital Jena, Friedrich-Schiller-University Jena, Germany (2403-10/08, November 6th, 2008) and subsequently by the ethics committees of all recruiting study centers.

In this observational, longitudinal case-cohort study, patients are enrolled within 48 hours of hospitalization 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 live style information. Upon enrollment, Pneumonia Severity Index (PSI) and CURB-65 are determined. For the day of enrollment and 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 six 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, and a quality of life questionnaire.

Analysis of cross sectional and time series data will identify clinical, genetic, and other molecular markers predicting a severe course of pneumonia in the hospital. Analysis of multilevel 'omics data in conjunction with clinical data will provide new insights into pathomechanistic details of pneumonia progression.

Study Timeline

• Study Start: 2009-08-25
• Study First Submitted: 2016-05-19
• Study First Submitted QC: 2016-05-24
• Study First Posted: 2016-05-25
• Primary Completion: 2022-06-01
• Study Completion: 2022-06-01
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-14
• Last Update Posted: 2022-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2309

Inclusion Criteria

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

2. Working diagnosis of CAP by enrolling physician

3. Adult patient >= 18 years of age

4. Valid informed consent form

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

Exclusion Criteria

1. Participation in this study at an earlier time
2. Hospitalization for any reason within 28 days prior to hospitalization for the current episode of CAP
3. More than 48 hours in the hospital before enrollment
4. Pregnancy
5. Breastfeeding
6. Decision on limitation of therapy before enrollment
7. Known HIV infection or AIDS
8. Anti-tumor treatment within the past six months
9. Post-stenotic pneumonia in conjunction with bronchial carcinoma
10. Therapy with corticosteroids ≥ 20mg for ≥ 14 days before enrollment
11. Non-steroidal immunosuppressive therapy within the past six months
12. Cytostatic therapy within the past six months
13. Radiation therapy within the past six months
14. Bone marrow transplant received
15. Respiratory support at home via tracheostoma
16. Cystic fibrosis
17. Active tuberculosis
18. Acute lung injury or acute respiratory distress syndrome for extrapulmonary reasons
19. Massive aspiration
20. Sepsis with extrapulmonary focus
21. Acute pulmonary embolism
22. Congestive heart failure New York Heart Association (NYHA) IV stadium
23. Liver insufficiency Child-Pugh C stadium

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
duration of hospitalization	up to one year after enrolment
All cause mortality	up to one year after enrolment
disease-specific mortality	up to one year after enrolment
duration of intensive care treatment	up to one year after enrolment
duration of ventilator assisted breathing	up to one year after enrolment

Trial Locations

Locations (64)

Universitätsklinikum Regensburg, Klinik Innere Medizin I, Intensivmedizin, Endokrinologie; 🇩🇪 Regensburg, Germany

Altmark-Klinikum gGmbH, Krankenhaus Salzwedel; 🇩🇪 Salzwedel, Germany

Krankenhaus Bethanien gGmbH Solingen, Abt. Pneumologie; 🇩🇪 Solingen, Germany

HELIOS Klinikum Wuppertal, Klinik für Intensivmedizin; 🇩🇪 Wuppertal, Germany

HELIOS Kliniken Schwerin GmbH, Klinik für Internistische und Neurologische Intensivmedizin/Stroke Unit; 🇩🇪 Schwerin, Germany

Universitätsklinikum Ulm, Klinik für Innere Medizin II, Sudienzentrale Innere II, Sektion Pneumologie; 🇩🇪 Ulm, Germany

Evangelisches Krankenhaus Bad Dürkheim, Innere Medizin; 🇩🇪 Bad Dürkheim, Germany

Hochtaunus-Kliniken, Medizinische Klinik III; 🇩🇪 Bad Homburg, Germany

Lungenklinik Ballenstedt/Harz gGmbH, Ev. Fachkrankenhaus f. Lungenkrankheiten; 🇩🇪 Ballenstedt, Germany

Charité - Universitätsmedizin Berlin, Zentrum Anästhesiologie und Intensivmedizin; 🇩🇪 Berlin, Germany

Vivantes Netzwerk f. Gesundheit GmbH Vivantes Klinikum Neukölln, Klinik f. Innere Med. - Pneumologie u.Infektiologie - Thoraxzentrum; 🇩🇪 Berlin, Germany

Vivantes Klinikum Spandau, Kard., Pneum. und kons. Intensivmedizin; 🇩🇪 Berlin, Germany

Universitätsklinikum Aachen, Med. Klinik I (Pneumologie); 🇩🇪 Aachen, Germany

Universitätsklinikum des Saarlandes, Innere Medizin V; 🇩🇪 Homburg/Saar, Germany

Ev. Fachkrankenhaus für Atemwegserkrankungen; 🇩🇪 Neustadt, Germany

Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie; 🇩🇪 Rotenburg/Wümme, Germany

LKH-Univ. Klinikum Graz, UKIM Pulmologie; 🇦🇹 Graz, Austria

Allgemeines Krankenhaus der Stadt Linz, Abteilung Lungenheilkunde; 🇦🇹 Linz, Austria

Evangel. Krankenhausverein, Luisenhospital, Lungenzentrum; 🇩🇪 Aachen, Germany

Krankenhaus Bad Arolsen GmbH, Innere Medizin (Herz-, Kreislauf- u. Lungendiagnostik); 🇩🇪 Bad Arolsen, Germany

Med. Klinik d. Forschungszentrum Borstel, Fachkrankenhaus f. Lungenerkrankungen, Infektionen u. Allergien; 🇩🇪 Borstel, Germany

Städt. Klinikum Dessau, Innere Medizin; 🇩🇪 Dessau-Roßlau, Germany

Uniklinikum Greifswald, Zentrum für Innere Medizin B; 🇩🇪 Greifswald, Germany

Krankenhaus Angermünde, Klinik f. Innere Medizin / Pneumologie; 🇩🇪 Angermünde, Germany

Evangelisches Geriatriezentrum Berlin; 🇩🇪 Berlin, Germany

HELIOS Klinikum Berlin-Buch, Interdisziplinäres Notfallzentrum mit Rettungsstelle; 🇩🇪 Berlin, Germany

Humboldt-Klinikum Vivantes, Kardiologie und kons. Intensivmedizin; 🇩🇪 Berlin, Germany

Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie; 🇩🇪 Berlin, Germany

Knappschaftskrankenhaus Dortmund, Klinik für Pneumologie; 🇩🇪 Dortmund, Germany

Krankenhaus Martha-Maria Halle-Dölau, Klinik für Innere Medizin I; 🇩🇪 Halle (Saale), Germany

Universitätsklinikum Halle (Saale), Klinik für Innere Medizin III (Kardiologie, Pneumologie, Intensivmedizin, Angiologie); 🇩🇪 Halle (Saale), Germany

Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivtherapie; 🇩🇪 Jena, Germany

Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Infektiologie und Pneumologie; 🇩🇪 Berlin, Germany

Berufsgenossenschaftl. Universitätsklinikum Bergmannsheil GmbH, Klinik f. Pneumologie, Allergologie u. Schlafmedizin; 🇩🇪 Bochum, Germany

Evangelische Kliniken Bonn, Betriebsstätte Johanniter Krankenhaus, Innere Medizin II; 🇩🇪 Bonn, Germany

Franziskus Krankenhaus Linz, Innere Abteilung; 🇩🇪 Linz, Germany

Klinkum Heidenheim, Medizinische Klinik II & Innere Intensiv; 🇩🇪 Heidenheim, Germany

SRH Wald-Klinikum Gera gGmbH, Medizinische Klinik 2; 🇩🇪 Gera, Germany

St.Vincentius-Kliniken gAG, Med. Klinik IV / Pneumologie; 🇩🇪 Karlsruhe, Germany

Universität Leipzig, Innere Medizin, Neurologie und Dermatologie, Pneumologie / Studiensekretariat; 🇩🇪 Leipzig, Germany

Klinikum Dortmund gGmbH, Medizinische Klinik (Pneumologie / Infektiologie); 🇩🇪 Dortmund, Germany

Universitätsklinikum Carl Gustav Carus, TU Dresden, Medizinische Klinik 1 - Abteilung Pneumologie; 🇩🇪 Dresden, Germany

Evangelisches Krankenhaus Kalk gGmbH, Innere Medizin / Pneumologie; 🇩🇪 Köln, Germany

Kliniken d. Main-Taunus-Kreises, Klinik f. Pneumologie u. Allg. Innere Medizin; 🇩🇪 Hofheim, Germany

Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Med. Klinik III (Pneumologie); 🇩🇪 Lübeck, Germany

Städtisches Klinikum München GmbH - Klinikum Harlaching, Klinik für Gastroent., Pneum., intern. Akut- u. Intensivmedizin; 🇩🇪 München, Germany

Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover, Klinik für Pneumologie; 🇩🇪 Hannover, Germany

Universitätsklinikum Jena, Zentrum für Infektionsmedizin und Krankenhaushygiene, Studienabteilung; 🇩🇪 Jena, Germany

Universitätsklinikum Schleswig-Holstein - Campus Kiel, Medizin 1; 🇩🇪 Kiel, Germany

St. Vincenz und Elisabeth Hospital Mainz, Innere Medizin; 🇩🇪 Mainz, Germany

Universitätsmedizin Mannheim, Studienkoordinierungszentrum, 1. Medizinische Klinik; 🇩🇪 Mannheim, Germany

Universitätsklinikum Münster, Kardiologie 1; 🇩🇪 Münster, Germany

Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie; 🇩🇪 Leipzig, Germany

Christliches Krankenhaus Quakenbrück e. V., Med. Klinik (Abtl. Pneumologie, Allergologie, Schlafmedizin); 🇩🇪 Quakenbrück, Germany

Kreisklinik Trostberg, Innere Abteilung; 🇩🇪 Trostberg, Germany

HELIOS Klinikum Wuppertal, Pneumologie, Bergisches Lungenzentrum; 🇩🇪 Wuppertal, Germany

Missionsärztliche Klinik GmbH Würzburg, Innere Medizin (Pneumologie); 🇩🇪 Würzburg, Germany

Krankenhaus München-Neuperlach, Klinik für Kardiologie, Pneumologie und Internistische Intensivmedizin; 🇩🇪 München, Germany

Mathias-Spital Rheine, Klinik für Pneumologie und Thoraxonkologie; 🇩🇪 Rheine, Germany

Dietrich-Bonhoeffer-Klinikum, Klinik f. Innere Medizin 2 (Abt. Pulmologie); 🇩🇪 Neubrandenburg, Germany

Pius-Hospital Oldenburg, Klinik f. Innere Med., Abt. f. Pneumologie; 🇩🇪 Oldenburg, Germany

Brüderkrankenhaus St. Josef, Medizinische Klinik; 🇩🇪 Paderborn, Germany

ASKLEPIOS Klinik Wandsbek, 1. Medizinische Abteilung; 🇩🇪 Hamburg, Germany