Clinical trial NCT02782013: Study of Progression of Community Acquired Pneumonia in the Hospital
Official title: Study of Progression of Hospitalized Community Acquired Pneumonia - Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia
Sepsis
Shock, Septic
Keywords: community acquired 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: University of Leipzig
name: Jena University Hospital
name: University of Giessen
name: University Medicine Greifswald
name: Charite University, Berlin, Germany
name: German Federal Ministry of Education and Research
First posted: 2016-05-25
Enrollment: 2309
Sex: ALL
Minimum age (years): 18
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 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.

Eligibility criteria: 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

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 enrolment
measure: disease-specific mortality
timeFrame: up to one year after enrolment
measure: duration of hospitalization
timeFrame: up to one year after enrolment
measure: duration of intensive care treatment
timeFrame: up to one year after enrolment
measure: duration of ventilator assisted breathing
timeFrame: up to one year after enrolment
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LKH-Univ. Klinikum Graz, UKIM Pulmologie
city: Linz
country: Austria
facility: Allgemeines Krankenhaus der Stadt Linz, Abteilung Lungenheilkunde
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Med. Klinik I (Pneumologie)
city: Aachen
country: Germany
facility: Evangel. Krankenhausverein, Luisenhospital, Lungenzentrum
city: Angermünde
country: Germany
facility: Krankenhaus Angermünde, Klinik f. Innere Medizin / Pneumologie
city: Bad Arolsen
country: Germany
facility: Krankenhaus Bad Arolsen GmbH, Innere Medizin (Herz-, Kreislauf- u. Lungendiagnostik)
city: Bad Dürkheim
country: Germany
facility: Evangelisches Krankenhaus Bad Dürkheim, Innere Medizin
city: Bad Homburg
country: Germany
facility: Hochtaunus-Kliniken, Medizinische Klinik III
city: Ballenstedt
country: Germany
facility: Lungenklinik Ballenstedt/Harz gGmbH, Ev. Fachkrankenhaus f. Lungenkrankheiten
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Zentrum Anästhesiologie und Intensivmedizin
city: Berlin
country: Germany
facility: Vivantes Netzwerk f. Gesundheit GmbH Vivantes Klinikum Neukölln, Klinik f. Innere Med. - Pneumologie u.Infektiologie - Thoraxzentrum
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch, Interdisziplinäres Notfallzentrum mit Rettungsstelle
city: Berlin
country: Germany
facility: Evangelisches Geriatriezentrum Berlin
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: Vivantes Klinikum Spandau, Kard., Pneum. und kons. Intensivmedizin
city: Berlin
country: Germany
facility: Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie
city: Bochum
country: Germany
facility: Berufsgenossenschaftl. Universitätsklinikum Bergmannsheil GmbH, Klinik f. Pneumologie, Allergologie u. Schlafmedizin
city: Bonn
country: Germany
facility: Evangelische Kliniken Bonn, Betriebsstätte Johanniter Krankenhaus, Innere Medizin II
city: Borstel
country: Germany
facility: Med. Klinik d. Forschungszentrum Borstel, Fachkrankenhaus f. Lungenerkrankungen, Infektionen u. Allergien
city: Dessau-Roßlau
country: Germany
facility: Städt. Klinikum Dessau, Innere Medizin
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH, Medizinische Klinik (Pneumologie / Infektiologie)
city: Dortmund
country: Germany
facility: Knappschaftskrankenhaus Dortmund, Klinik für Pneumologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, TU Dresden, Medizinische Klinik 1 - Abteilung Pneumologie
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera gGmbH, Medizinische Klinik 2
city: Greifswald
country: Germany
facility: Uniklinikum Greifswald, Zentrum für Innere Medizin B
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle-Dölau, Klinik für Innere Medizin I
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale), Klinik für Innere Medizin III (Kardiologie, Pneumologie, Intensivmedizin, Angiologie)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale
city: Hamburg
country: Germany
facility: ASKLEPIOS Klinik Wandsbek, 1. Medizinische Abteilung
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Pneumologie
city: Heidenheim
country: Germany
facility: Klinkum Heidenheim, Medizinische Klinik II & Innere Intensiv
city: Hofheim
country: Germany
facility: Kliniken d. Main-Taunus-Kreises, Klinik f. Pneumologie u. Allg. Innere Medizin
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum des Saarlandes, Innere Medizin V
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivtherapie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Zentrum für Infektionsmedizin und Krankenhaushygiene, Studienabteilung
city: Karlsruhe
country: Germany
facility: St.Vincentius-Kliniken gAG, Med. Klinik IV / Pneumologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Kiel, Medizin 1
city: Köln
country: Germany
facility: Evangelisches Krankenhaus Kalk gGmbH, Innere Medizin / Pneumologie
city: Leipzig
country: Germany
facility: Universität Leipzig, Innere Medizin, Neurologie und Dermatologie, Pneumologie / Studiensekretariat
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie
city: Linz
country: Germany
facility: Franziskus Krankenhaus Linz, Innere Abteilung
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Med. Klinik III (Pneumologie)
city: Mainz
country: Germany
facility: St. Vincenz und Elisabeth Hospital Mainz, Innere Medizin
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, Studienkoordinierungszentrum, 1. Medizinische Klinik
city: München
country: Germany
facility: Städtisches Klinikum München GmbH - Klinikum Harlaching, Klinik für Gastroent., Pneum., intern. Akut- u. Intensivmedizin
city: München
country: Germany
facility: Krankenhaus München-Neuperlach, Klinik für Kardiologie, Pneumologie und Internistische Intensivmedizin
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Kardiologie 1
city: Neubrandenburg
country: Germany
facility: Dietrich-Bonhoeffer-Klinikum, Klinik f. Innere Medizin 2 (Abt. Pulmologie)
city: Neustadt
country: Germany
facility: Ev. Fachkrankenhaus für Atemwegserkrankungen
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg, Klinik f. Innere Med., Abt. f. Pneumologie
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef, Medizinische Klinik
city: Quakenbrück
country: Germany
facility: Christliches Krankenhaus Quakenbrück e. V., Med. Klinik (Abtl. Pneumologie, Allergologie, Schlafmedizin)
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik Innere Medizin I, Intensivmedizin, Endokrinologie
city: Rheine
country: Germany
facility: Mathias-Spital Rheine, Klinik für Pneumologie und Thoraxonkologie
city: Rotenburg/Wümme
country: Germany
facility: Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie
city: Salzwedel
country: Germany
facility: Altmark-Klinikum gGmbH, Krankenhaus Salzwedel
city: Schwerin
country: Germany
facility: HELIOS Kliniken Schwerin GmbH, Klinik für Internistische und Neurologische Intensivmedizin/Stroke Unit
city: Solingen
country: Germany
facility: Krankenhaus Bethanien gGmbH Solingen, Abt. Pneumologie
city: Trostberg
country: Germany
facility: Kreisklinik Trostberg, Innere Abteilung
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Klinik für Innere Medizin II, Sudienzentrale Innere II, Sektion Pneumologie
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, Klinik für Intensivmedizin
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, Pneumologie, Bergisches Lungenzentrum
city: Würzburg
country: Germany
facility: Missionsärztliche Klinik GmbH Würzburg, Innere Medizin (Pneumologie)
Study officials:
affiliation: Charite University, Berlin, Germany
name: Norbert Suttorp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosolowski M, Oberle V, Ahnert P, Creutz P, Witzenrath M, Kiehntopf M, Loeffler M, Suttorp N, Scholz M. Dynamics of cytokines, immune cell counts and disease severity in patients with community-acquired pneumonia - Unravelling potential causal relationships. Cytokine. 2020 Dec;136:155263. doi: 10.1016/j.cyto.2020.155263. Epub 2020 Sep 4.
citation: Ahnert P, Creutz P, Horn K, Schwarzenberger F, Kiehntopf M, Hossain H, Bauer M, Brunkhorst FM, Reinhart K, Volker U, Chakraborty T, Witzenrath M, Loffler M, Suttorp N, Scholz M; PROGRESS Study Group. Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study. Crit Care. 2019 Apr 4;23(1):110. doi: 10.1186/s13054-019-2316-x.
citation: Ahnert P, Creutz P, Scholz M, Schutte H, Engel C, Hossain H, Chakraborty T, Bauer M, Kiehntopf M, Volker U, Hammerschmidt S, Loeffler M, Suttorp N; PROGRESS study group. PROGRESS - prospective observational study on hospitalized community acquired pneumonia. BMC Pulm Med. 2016 Jul 28;16(1):108. doi: 10.1186/s12890-016-0255-8.