"Escape 10 Study. Epidemiology and Determinants of Outcomes of Severe Community-acquired Pneumonia in the Elderly"
Conditions: Severe Community-Acquired Pneumonia (sCAP), Elderly Infection, Community-Acquired Infections, Health Care Quality, Access, and Evaluation
Sponsor: Joan Sabater Riera

ESCAPE 10 study protocol                                                                version 2, 1st April 2025 
 
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Study Protocol 
 
ESCAPE 10 STUDY 
Epidemiology and determinants of outcomes of Severe Community 
Acquired Pneumonia in the Elderly  
 
 
 
- 
Study Promotor: Study Group Infections in the Elderly (ESGIE), European 
Society 
of 
Clinical 
Microbiology 
and 
Infectious 
Diseases 
ESCMID. 
Aeschenvorstadt 55, 4051 Basel, SWITZERLAND 
 
- 
Principal Investigator: Professor Jordi Rello. Science Officer, European Study 
Group Infections in the Elderly. ESCMID. Email: jrello@crips.es 
 
 
 
 
 
 
 

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- 
Co-ordinating site: Critical Care Department, Bellvitge University Hospital, 
L’Hospitalet de Llobregat, Barcelona, Spain. 
- 
Study Coordinator: Dr. África Lores-Obradors, Critical Care Department, 
Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. 
africa.lores@gmail.com. 
- 
Statistics 
and 
Bioinformatics 
Support: 
Anna 
Sanjuan-Vilaplana. 
anna.sanjuan@vhir.org 
 
 
- 
The Steering Committee: 
o Emine Alp Meşe (TK).  
o Jordi Rello (SP).  
o Virginie Prendki (CH). 
o Joan Sabater-Riera (SP). 
o Despoina Koulenti (UK).  
o Paraskevi Fragkou (GR).  
 
 
 
 
 
 Protocol Version 2.          
1st April 2025 

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STUDY SYNOPSIS 
BACKGROUND AND RATIONALE 
STUDY DESIGN  
Study Type 
Study Population 
Definitions  
Inclusion criteria 
Exclusion criteria 
Sample Size and inclusion periods 
METHODS 
Procedures & recruitment methods 
Primary outcome 
Secondary outcomes 
Objectives: 
Data collection 
Statistical analysis plan 
ETHICAL CONSIDERATIONS 
FUNDING  
RESULTS DISSEMINATION 
REFERENCES 
 
 

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1. STUDY SYNOPSIS 
Title:  
Epidemiology and determinants of outcomes of 
Severe Community Acquired Pneumonia in the 
Elderly.  
Acronym: 
ESCAPE 10 STUDY. 
Version and date of protocol:  
 
Version 2, 1th April 2025. 
Study Promotor: 
Study Group Infections in the Elderly (ESGIE), 
European Society of Clinical Microbiology and 
Infectious Diseases ESCMID. 
Principal Investigator: 
Jordi Rello. 
ClinicalTrials.Gov: 
Pending.  
Medical condition under investigation:  Severe Community-Acquired Pneumonia in the 
Elderly. 
Study Type: 
Multinational, observational, retrospective cohort 
study. 
Inclusion criteria: 
 
1.Patients aged 65 years-old or older. 
2.Patients with clinically and radiologically (Chest X-
Ray (CXR), Computerized Tomography (CT) or lung 
ultrasound (LUS) confirmed pneumonia. 
3.Patients fulfilling the protocol definition of sCAP 
Exclusion criteria: 
 
 
1.Patients aged below the inclusion threshold (65 
years old). 
2.Recent hospitalization (above 48 h within the past 
10 days) in acute healthcare settings. 
3.Terminal events. 
4.Patients receiving comfort care only or with 
documented decisions to forgo intensive medical 
interventions. 
 
Sample Size and inclusion periods:  
 
At least 500 patients will be enrolled over a period 
of 13 months (between January 1, 2024, and 
January 31, 2025). Each recruiting center will enroll 
20 patients: 10 during the winter influenza epidemic 
period and 10 during the non-epidemic (summer) 
period.  
Primary outcome: 
 
28-day mortality. 
Secondary outcomes: 
1. Assessment of “Indicators and Standards of 
Quality in the Care and Medical Management of 
Patients with sCAP” 
2.Case fatality rate. 

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3.Overall (all-cause) mortality. 
4.Ιn-hospital (all cause) mortality. 
5.Pneumonia-attributed in-hospital mortality. 
6.Length of hospital stay (LOS). 
7.Duration of ICU / High-dependency unit/ IMCU 
stay. 
8.Duration of mechanical ventilation and ventilation-
free days. 
9.Rate of pneumonia-related complications: 
Ventilation Associated Pneumonia (VAP), 
Empyema, Acute Respiratory Distress Syndrome 
(ARDS), Bacteraemia, Septic Shock. 
10.Frequency of delirium, Renal Replacement 
Therapy and quality indicators. 
11.Identification of risk factors associated with 
adverse outcomes in sCAP. 
12.Discharge status after stay in acute unit: Home, 
Nursing home, Rehabilitation. 
13.Functional status at discharge. 
14.Cognitive function at discharge.  
Objectives: 
 
1. To obtain a comprehensive overview of the 
epidemiology of the sCAP pathogen and its 
relationship with geographic locations, countries, 
seasonality, coexistence with epidemic influenza 
periods, and patient outcomes in the post-COVID 
era. 
2.To identify a set of quality indicators to be used as 
standard of care. 
3.To assess gender differences in the epidemiology 
of sCAP in the elderly, to refine precision medicine 
management. 
4.To identify clinical sub-phenotypes or endotypes 
associated with different outcomes. 
5.To develop an educational tool to improve care 
and safety based on evidence identified by this 
study. 
 
 
 
 
 
 

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2. BACKGROUND AND RATIONALE 
Community-Acquired Pneumonia (CAP) is one of the most common infections, with an 
incidence ranging from 1 to 25 cases per 1,000 inhabitants per year [1]. Severe CAP 
(sCAP) represents its most lethal form and is associated with high mortality and morbidity 
rates [1]. 
Elderly patients constitute a highly heterogeneous group; yet they are significantly more 
predisposed to severe disease compared to younger individuals [2]. This increased 
vulnerability is attributed to the higher prevalence of comorbidities and the natural decline 
in immune function, known as immuno-senescence, that accompanies aging, reducing 
the differences between immunocompromised and immunocompetent in aging cohorts. 
Indeed, older age has been identified as an independent risk factor for severe disease 
[3], with mortality rates reported to range from 40% to 55.6% [4,5]. Gender differences in 
the incidence and pathogens of CAP have been reported [6] and a gender approach 
(SAGER guidelines) is required. However, no relevant data for sCAP in the post-COVID-
19 era are known. There is a lack of quality indicators and identification of clinical sub-
phenotypes. 
While sCAP is a relatively common condition with a profound impact on the elderly 
population, there remains a disproportionately low number of observational studies 
examining outcomes and potential risk factors in this group. Identifying and characterizing 
risk factors associated with unfavorable outcomes in this heterogeneous population is 
crucial to optimizing treatment and improving care strategies. 

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Conducted across an international network of European countries, the 'Epidemiology and 
Determinants of Outcomes of Severe Community-Acquired Pneumonia in the Elderly 
(ESCAPE 10 study) is a quality improvement initiative aiming at identifying areas for 
improvement in patient care and management and ensuring better short-term clinical 
outcomes for elderly patients with sCAP, as well as improving efficiency, safety, and 
patient satisfaction. 
This study takes into account seasonal variations in sCAP etiology and its association 
with the coexistence of epidemic influenza periods. 
 
 
3. STUDY DESIGN  
Study Type 
The ESCAPE 10 study is a multinational, observational, retrospective cohort study aimed 
at obtaining a comprehensive overview of the epidemiology of the sCAP pathogen and 
its relationship with geographic locations, countries, seasonality, coexistence with 
epidemic influenza periods, and patient outcomes in the post-COVID era. Additionally, 
the study focuses on improving the quality of patient care and short-term outcomes in 
elderly patients with sCAP. The primary emphasis will be on quality indicators and 
standards, as outlined in the Definitions section 
The study will be conducted in countries with markedly different demographic and 
socioeconomic characteristics. The co-ordinating site will be the Critical Care 
Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. 
The Steering Committee is composed by Emine Alp Meşe (TK), Jordi Rello (SP), 

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Virginie Prendki (CH), Joan Sabater-Riera (SP), Despoina Koulenti (UK) & Paraskevi 
Fragkou (GR). JR & JSR are representing the Pneumonia ICP network from Centros de 
Investigación en Red de Enfermedades Respiratorias del Instituto de Salut Carlos III 
(CIBERES-SCIII). JR & VP are representing the ESGIE, DK Is representing Study Group 
for Infections in Critically Ill Patients (ESGCIP), PF is representing Study Group for 
Respiratory Viruses (ESGREV) and EA is representing European Committee on Infection 
Control (EUCIC), who is endorsing the study. 
 
Study Population 
Elderly patients who fulfill the following inclusion and exclusion criteria and definitions 
could be enrolled in the study.  
 
Definitions  
1. Elderly: Patients aged 65 years and older. 
2. Severe CAP: Community-acquired pneumonia (CAP) is considered as an acute 
infection of lung parenchyma which was acquired in the community in patients with 
no recent hospitalization in acute healthcare settings. Severe CAP (sCAP) is 
defined as the CAP patients admitted in an acute hospital as they might require 
organ support [adapted from 1]. For the purposes of this study, patients with 
immunosuppression, aspiration pneumonia or residing in nursing homes will be 
enrolled to have a picture of the real-world, and they will have a differential sub-
analysis. Differentiation between patients requiring a) ward hospitalization, b) high-
dependency unit and c) ICU will be done. 

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3. Indicators and Standards of Quality [7-10] in the Care and Medical 
Management of Patients with sCAP:  
Diagnosis and Evaluation The identification of CAP should be based on clinical 
and radiological criteria, using risk stratification scales 
such as CURB-65, SOFA and PIRO scores to 
determine the severity of the disease. 
Antibiotic Treatment 
 
Quality indicators include the initiation of empirical 
antibiotic treatment is recommended within 6 hours 
after the initial evaluation of the patient. The selection 
of antibiotics should be compliant with clinical 
guidelines that consider local antimicrobial resistance 
and patient characteristics. 
Monitoring and Follow-up 
 
It is essential to assess the clinical response to 
treatment within 48-72 hours.  
Clinical Outcomes 
 
Quality indicators include mortality rates and hospital 
readmissions, as well as improvement in patient quality 
of life after treatment. 
Prevention 
 
Promotion of vaccination, including pneumococcal 
vaccine and influenza vaccine, is essential for the 
prevention of CAP. 
 

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Inclusion criteria: 
Patients will be included if they fulfill all the following criteria: 
1. Patients aged 65 years-old or older. 
2. Patients 
with 
clinically 
and 
radiologically 
(Chest 
X-Ray 
(CXR), 
Computerized Tomography (CT) or lung ultrasound (LUS) confirmed 
pneumonia. 
3. Patients fulfilling the protocol definition of sCAP. 
Exclusion criteria: 
Patients will be excluded if they fulfill at least one of the following criteria: 
1. Patients aged below the inclusion threshold (65 years old). 
2. Recent hospitalization (above 48 h within the past 10 days) in acute 
healthcare settings. 
3. Terminal events. 
4. Patients receiving comfort care only or with documented decisions to forgo 
intensive medical interventions. 
 
Sample Size and inclusion periods.  
We aim to include at least 500 patients. However, rather than targeting a specific sample 
size, we will follow a predefined 13-month (between January 1, 2024, and January 31, 
2025) recruitment period to minimize bias associated with the seasonality of certain 
respiratory pathogens. Each recruiting center will include 20 patients: 10 during the winter 
influenza epidemic period and 10 during the non-epidemic (summer) period to obtain a 
balanced representation. 

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The study sample size has been determined arbitrarily. It is expected that each ESGIE 
member will include approximately 15–20 patients. 
 
 
4. METHODS. 
Procedures & recruitment methods. 
This retrospective international observational quality improvement study aims to collect 
and analyze data from elderly patients with severe community-acquired pneumonia 
(sCAP) To obtain a comprehensive overview of the epidemiology of the sCAP pathogen 
and its relationship with geographic locations, countries, seasonality, coexistence with 
epidemic influenza periods, and patient outcomes in the post-COVID era and identify 
opportunities for enhancing patient care, safety and satisfaction. Elderly patients admitted 
to the participating hospitals who meet the sCAP definition (outlined in the Definitions 
section), fulfill all inclusion criteria, and have no exclusion criteria could be enrolled. We 
will ensure adequate representation of male and female study participants. The 
recruitment period will span 8 months during the previously described periods.  
Required data will be collected from electronic and/or paper medical records, and reviews 
of laboratory and radiology results. Follow-up will be conducted on Day 7 (±1), Day 28 
(±2), since study enrollment if patients remain hospitalized. No interventions or sample 
collections are planned as part of this study as it is a retrospective study. 
 
Primary outcome. 
The primary outcome of the ESCAPE 10 study will be 28-day mortality. 

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Secondary outcomes: 
Additional outcomes will be: 
1. assessment of “Indicators and Standards of Quality in the Care and Medical 
Management of Patients with sCAP” as shown in the Definitions. 
2. Case fatality rate. 
3. Overall (all-cause) mortality. 
4. Ιn-hospital (all cause) mortality. 
5. Pneumonia-attributed in-hospital mortality. 
6. Length of hospital stay (LOS). 
7. Duration of ICU / High-dependency unit/ IMCU stay. 
8. Duration of mechanical ventilation and ventilation-free days. 
9. Rate of pneumonia-related complications: Ventilation Associated Pneumonia 
(VAP), Empyema, Acute Respiratory Distress Syndrome (ARDS), Bacteremia, 
Septic Shock. 
10. Frequency of delirium, Renal Replacement Therapy and quality indicators. 
11. Identification of risk factors associated with adverse outcomes in sCAP. 
12. Discharge status after stay in acute unit: Home, Nursing home, Rehabilitation. 
13. Functional status at discharge. 
14. Cognitive function at discharge. 
 
Objectives: 

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1.To obtain a comprehensive overview of the epidemiology of the sCAP pathogen and its 
relationship with geographic locations, countries, seasonality, coexistence with epidemic 
influenza periods, and patient outcomes in the post-COVID era. 
2. To identify a set of quality indicators to be used as standard of care. 
3.To assess gender differences in the epidemiology of sCAP in the elderly, to refine 
precision medicine management. 
4.To identify clinical sub-phenotypes or endotypes associated with different outcomes. 
5.To develop an educational tool to improve care and safety based on evidence identified 
by this study. 
 
Data collection. 
Data from this study will be collected in coded form, recorded and stored using REDCap 
(Research Electronic Data Capture). Each participant will be identified by a unique code 
automatically generated in REDCap, guaranteeing the dissociation of personal and 
clinical data. Each recruiting centre will have a protected equivalence table where each 
study patient will be collected and identified in REDCap with their identification data. Only 
one researcher from each centre with expertise in data management will have access. 
REDCap is a secure web application designed to support data capture in research 
studies. It includes HIPAA Security Rule compliance features such as real-time validation 
of data entry (e.g. for data types and range checks), a full audit trail, user-based privileges 
and a mechanism for exporting “de-identified” data to statistical packages (SPSS, SAS, 
Stata and R). Access to study data in REDCap will be restricted to study team members 
with authentication via personal user credentials and email. 

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Data of interest include (but not limited to): data related to the quality indicators, 
demographic information (age, self-reported sex, body mass index, ethnicity, recent 
travels abroad, working status, high risk or suspicious contacts), past medical history 
(details of previous respiratory tract infections and hospitalizations, dental status, close 
contact with the healthcare system, immunization status, current medications, baseline 
functional, nutritional and mental status (and relevant scores), chronic/background 
conditions, presence of catheters), previous exposure to antibiotics, known history of 
multi-drug resistant organisms, list of symptoms and symptoms and signs, findings of 
physical examination, disease severity scores (for current infection), routine laboratory 
biomarkers, microbiological and imaging data, treatment and supportive care received 
during current episode and list of possible complications (All variables collected in the 
study can be found in Annex 1). 
 
Statistical analysis plan. 
Data will be reviewed for inconsistencies, missing values, and outliers. Missing data will 
be handled using multiple imputation or sensitivity analysis if appropriate. Patient 
demographics, comorbidities, clinical presentation, and laboratory/radiology findings will 
be summarized. Group comparisons (e.g., survivors vs. non-survivors) using chi-square 
or Fisher’s exact test for categorical variables and independent t-tests or Mann-Whitney 
U tests for continuous variables. For mortality, we will use Kaplan-Meier survival analysis 
for time-to-event data and cox proportional hazards regression to identify predictors of 
mortality. Logistic regression will be used to assess associations between baseline 
characteristics and adverse outcomes. Adjusted odds ratios (aOR) with 95% confidence 

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intervals (95% CI) will be reported. We will examine the relationships between 
laboratory/radiological parameters and clinical outcomes using Spearman or Pearson 
correlation. Sensitivity analysis will be performed if patient data are missing for certain 
variables and outcomes, to assess the robustness of the results and the impact of missing 
data on the study findings. A p-value <0.05 will be considered statistically significant and 
95% CI will be reported for estimates.  
 
 
5. ETHICAL CONSIDERATIONS. 
This is a retrospective study using anonymized data, which will not require informed 
consent. This study will be approved by the Research Ethics Committee of all participating 
institutions and will fully comply with the Declaration of Helsinki and the Sex and Gender 
Equity in Research (SAGER) Guidelines [11] as well as other locally relevant regulations. 
Participants’ data will be collected, analyzed and handled under strict anonymity. No risks, 
harms, direct benefits, or incentives are expected for participants from this study, as it is 
an observational retrospective study. Substantial changes to the project set-up, the 
protocol and any relevant project documents will be submitted to relevant Ethics 
Committees for approval before implementation. 
 
 
6. FUNDING.  

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This study will be initially funded by the research funds accessible to the principal 
investigator. Funding will be requested to cover the costs of study management and 
statistical analysis. 
 
 
7. RESULTS DISSEMINATION. 
Study findings will be submitted to high quality peer-reviewed journals and will be 
presented at national and international conferences and symposia, after approval by the 
Steering Committee. All authors should approve the final manuscript. The “ESCAPE 10 
study group investigators” will be constituted by two representatives from centers with at 
least 15 valid cases. List of authors for global papers will be constituted by the Steering 
Committee members plus three additional authors for the top recruiters sites, plus the list 
of “ESCAPE 10 study group investigators” reported in alphabetical order in an Appendix 
(two designed members by investigator site). Other contributors will be reported in 
acknowledgments. List of authors for national data will be constituted by the principal 
investigators plus two contributors from top 5 recruiters sites, plus a list of “COUNTRY 
ESCAPE 10 study group investigators” reported in alphabetical order in an Appendix (two 
designed members by investigator site). Other contributors will be reported in 
acknowledgments. Findings will also be shared among research collaborators and 
institutional networks to foster discussion and future research opportunities. 
 
 
8. REFERENCES. 

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[1] Martin-Loeches I, Torres A, Nagavci B, et al. ERS/ESICM/ESCMID/ALAT guidelines for the 
management of severe community-acquired pneumonia. Eur Respir J. 2023;61(4):2200735. 
Published 2023 Apr 3. doi:10.1183/13993003.00735-2022 
[2] Osman M, Manosuthi W, Kaewkungwal J, et al. Etiology, Clinical Course, and Outcomes of 
Pneumonia in the Elderly: A Retrospective and Prospective Cohort Study in Thailand. Am J Trop 
Med Hyg. 2021;104(6):2009-2016. Published 2021 May 3. doi:10.4269/ajtmh.20-1393 
[3] Mahendra M, Jayaraj BS, Limaye S, Chaya SK, Dhar R, Mahesh PA. Factors influencing 
severity 
of 
community-acquired 
pneumonia. 
Lung 
India. 
2018;35(4):284-289. 
doi: 
10.4103/lungindia.lungindia_334_17 
[4] Rello J, Rodriguez R, Jubert P, Alvarez B. Severe community-acquired pneumonia in the 
elderly: epidemiology and prognosis. Study Group for Severe Community-Acquired Pneumonia. 
Clin Infect Dis. 1996;23(4):723-728. doi:10.1093/clinids/23.4.723 
[5] Hu HC, Huang CC, Tsai YH, Lee CH, Hsieh MJ. Outcome analysis of patients requiring 
mechanical ventilation with severe community-acquired pneumonia and identified bacterial 
pathogens. Chang Gung Med J. 2005;28(4):229-236. 
[6] Gonzalez Quero, Beatriz, Leyre Serrano Fernandez, and Marta Garcia Moyano. "Differences 
in Community-Acquired Pneumonia According to Gender." European Respiratory Journal, vol. 
50, suppl. 61, 2017, PA4101. https://doi.org/10.1183/1393003.congress-2017.PA4101. 
[7] Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity 
on presentation to hospital: an international derivation and validation study. Thorax. 
2003;58(5):377-382. doi:10.1136/thorax.58.5.377 
[8] Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-
acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and 
Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. 
doi:10.1164/rccm.201908-1581ST 

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[9] World Health Organization. "Vaccination: European Commission and World Health 
Organization Join Forces to Promote the Benefits of Vaccines." World Health Organization, 12 
Sept. 2019, https://www.who.int/news/item/12-09-2019-vaccination-european-commission-and-
world-health-organization-join-forces-to-promote-the-benefits-of-vaccines. 
[10] Blot SI, Rodriguez A, Solé-Violán J, et al. Effects of delayed oxygenation assessment 
on time to antibiotic delivery and mortality in patients with severe community-acquired pneumonia. 
Crit Care Med. 2007;35(11):2509-2514. doi: 10.1097/01.CCM.0000287587.43801.9C 
[11] EASE. SAGER Guidelines: Sex and Gender Equity in Research – SAGER Checklist (2022 
Update). European Association of Science Editors, 2022, https://ease.org.uk/wp-
content/uploads/2023/01/EASE-SAGER-Checklist-2022.pdf.