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

• ClinicalTrials.gov Identifier: NCT05688774
• Recruitment Status: Recruiting
• First Posted: January 18, 2023
• Last Update Posted: January 18, 2023
• Sponsor: Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps
• Collaborators: Charite University, Berlin, Germany; University of Leipzig; Jena University Hospital
• Information provided by (Responsible Party): Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps

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
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
• Estimated 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: February 28, 2022
• Estimated Primary Completion Date: February 28, 2024
• Estimated Study Completion Date: February 28, 2025

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. All cause mortality [ Time Frame: up to one year after enrollment ]
2. disease-specific mortality [ Time Frame: up to one year after enrollment ]
3. duration of hospitalization [ Time Frame: up to one year after enrollment ]
4. duration of intensive care treatment [ Time Frame: up to one year after enrollment ]
5. duration of ventilator assisted breathing [ Time Frame: up to one year after enrollment ]

Biospecimen Retention:   Samples With DNA

DNA from EDTA whole blood, RNA from stabilized whole blood, serum, citrate plasma, stabilized EDTA plasma, urin

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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
   • Congestive heart failure New York Heart Association (NYHA) IV stadium
   • Liver insufficiency Child-Pugh C stadium

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. Post-stenotic pneumonia in conjunction with bronchial carcinoma
6. Active tuberculosis
7. Acute lung injury or acute respiratory distress syndrome for extrapulmonary reasons
8. Massive aspiration
9. Sepsis with extrapulmonary focus
10. Acute pulmonary embolism

Contacts and Locations

Contacts

Contact: Sarah Berger, MD; +49-30-450553347; sarah.berger@charite.de

Contact: Peter Ahnert, MD; +49-341-9716282; peter.ahnert@imise.uni-leipzig.de

Locations

Germany

Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Infektiologie und Pneumologie; Recruiting

Berlin, Germany, 13353

Gemeinschaftskrankenhaus Havelhöhe, Kardio-Pneumologie; Recruiting

Berlin, Germany, 14089

Städtisches Klinikum Dessau, Innere Medizin; Recruiting

Dessau, Germany, 06847

Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, Pneumologische Studienzentrale; Recruiting

Hamburg, Germany, 20246

Klinikum St. Georg gGmbH, Klinik für Infektions-/Tropenmedizin und Nephrologie; Recruiting

Leipzig, Germany, 04129

Universitätsklinikum Gießen und Marburg, Klinik für Pneumologie und Anästhesie; Recruiting

Marburg, Germany, 35043

Universitätsklinikum Münster, Kardiologie 1; Recruiting

Münster, Germany, 48149

Diakoniekrankenhaus Rotenburg(Wümme)gGmbH, Zentrum für Pneumologie; Recruiting

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

Investigators

• Principal Investigator: Norbert Suttorp, MD; Charité Univerity, Berlin, Germany

More Information

• Responsible Party: Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps
• ClinicalTrials.gov Identifier: NCT05688774
• Other Study ID Numbers: PROGRESS-COMORB
• First Posted: January 18, 2023
• Last Update Posted: January 18, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual participant data will be made available after conclusion of the study. Participants can apply for clinical and molecular study data by sending structured project proposals to the PROGRESS board. The PROGRESS board will evaluate proposals for scientific quality, adherence to the limits set by patient's informed consent statements and by intellectual property regulations of the funding agency. Proposals shall not be denied without concrete reason.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Seps:

community ascquired pneumonia; CAP; disease progression

Additional relevant MeSH terms:

Pneumonia; Sepsis; Shock, Septic; Disease Progression; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Disease Attributes; Shock