Advanced Understanding of Staphylococcus Aureus and Pseudomonas Aeruginosa Infections in EuRopE - ICU (ASPIRE-ICU)

• ClinicalTrials.gov Identifier: NCT02413242
• Recruitment Status: Completed
• First Posted: April 9, 2015
• Last Update Posted: May 8, 2019
• Sponsor: Jan Kluytmans
• Collaborators: MedImmune LLC; Universiteit Antwerpen
• Information provided by (Responsible Party): Jan Kluytmans, UMC Utrecht

Study Description

Brief Summary:

Intensive Care Unit (ICU) acquired pneumonia, including ventilator-associated pneumonia, is a frequently occurring health-care associated infection, which causes considerable morbidity, mortality and health care costs. Important pathogens causing ICU pneumonia are Staphylococcus aureus and Pseudomonas aeruginosa. The epidemiology of ICU pneumonia and patient-related and contextual factors is not fully described, but is urgently needed to support the development of effective interventions.

Condition or disease	Intervention/treatment
Pneumonia; Pneumonia, Ventilator-Associated; Nosocomial Pneumonia	Other: Various observed exposure(s) of interest

Study Design

• Study Type: Observational
• Actual Enrollment: 2031 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Advanced Understanding of Staphylococcus Aureus and Pseudomonas Aeruginosa Infections in EuRopE - ICU
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: April 30, 2019
• Actual Study Completion Date: April 30, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
ICU subjects, S. aureus+ at ICU admission; Adult ICU patients, with a positive colonization status for S. aureus at ICU admission, who are mechanically ventilated within 24 hours of ICU admission and have an expected length of stay of 48h or more. Colonization status will be measured at ICU admission using a nose swab and an ETA (or sputum/throat if unavailable). Positivity of either of the two qualifies the patient to be enrolled as a subject in this group.	Other: Various observed exposure(s) of interest; A risk prediction model will be developed to assess which risk factors are associated with the development of ICU pneumonia during ICU stay
ICU subjects, S. aureus- at ICU admission; Adult ICU patients, with a negative colonization status for S. aureus at ICU admission, who are mechanically ventilated within 24 hours of ICU admission and have an expected length of stay of 48h or more. Colonization status will be measured at ICU admission using a nose swab and an ETA (or sputum/throat if unavailable). Negativity of both qualifies the patient to be enrolled as a subject in this group.	Other: Various observed exposure(s) of interest; A risk prediction model will be developed to assess which risk factors are associated with the development of ICU pneumonia during ICU stay

Outcome Measures

Primary Outcome Measures :

1. Incidence of S. aureus ICU pneumonia [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
2. Incidence of P. aeruginosa ICU pneumonia [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]

Secondary Outcome Measures :

1. Prevalence of S. aureus / P. aeruginosa colonization [ Time Frame: at ICU admission ]
2. Incidence of all cause ICU pneumonia [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
3. Incidence of S. aureus ICU pneumonia stratified by MRSA vs. MSSA [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
4. Incidence of P. aeruginosa ICU pneumonia stratified by MDR-PA vs. S-PA [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
5. Incidence of ICU bacteremia per etiologic agent (in case of S. aureus and/or P. aeruginosa and for all clinically relevant other pathogens) [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
6. All-cause mortality [ Time Frame: date of ICF until ICU discharge (on average 7 days after ICF) ]
7. All-cause mortality [ Time Frame: At day 30 after ICU admission ]
8. All-cause mortality [ Time Frame: At day 90 after ICU admission ]
9. Time to S. aureus ICU pneumonia [ Time Frame: day of ICU admission until ICU discharge (on average 7 days after ICU admission) ]
10. Time to P. aeruginosa ICU pneumonia [ Time Frame: day of ICU admission until ICU discharge (on average 7 days after ICU admission) ]
11. Time to all cause ICU pneumonia [ Time Frame: day of ICU admission until ICU discharge (on average 7 days after ICU admission) ]
12. Time to all cause ICU bacteremia [ Time Frame: day of ICU admission until ICU discharge (on average 7 days after ICU admission) ]
13. Time to death of any cause [ Time Frame: day of ICU admission until day 90 or ICU discharge, whichever comes first ]

Other Outcome Measures:

1. Magnitude of healthcare utilization as measured by: a. Duration of ICU stay including readmissions [ Time Frame: day of ICU admission until day 30 after ICU discharge ]
2. Magnitude of healthcare utilization as measured by: b. Days on mechanical ventilation [ Time Frame: day of ICU admission until ICU discharge (on average 9 days after ICU admission) ]
3. Magnitude of healthcare utilization as measured by: c. Days of antibiotic usage [ Time Frame: day of ICU admission until ICU discharge (on average 9 days after ICU admission) ]
4. Magnitude of healthcare utilization as measured by: d. Duration of hospital stay, including readmissions [ Time Frame: day of ICU admission until ICU discharge (on average 9 days after ICU admission) ]
5. Incidence of S. aureus colonization [ Time Frame: from day of ICU admission until onset of ICU pneumonia (on average 7 days after ICU admission) ]
6. Incidence of P. aeruginosa colonization [ Time Frame: from day of ICU admission until onset of ICU pneumonia (on average 7 days after ICU admission) ]

Biospecimen Retention:   Samples Without DNA

• Microbiological samples:

  • Nose swabs - at day of informed consent form (ICF), day 4, day 7.
  • Peri-anal swabs - at day of ICF, day 4, day 7, then twice weekly until day 30.
  • Lower respiratory tract (LRT) sample - at day of ICF, day 4, day 7, then twice weekly until day 30, day of ICU pneumonia, day 7 after ICU pneumonia. The LRT sample can be defined as the collection of an endotracheal aspirate (ETA). If an ETA cannot be collected, a sputum sample may be taken.
  • Broncho alveolar lavage - If available through clinical procedures, BAL specimens will be collected for study purposes.
• Blood samples * Blood samples will be taken at day of ICF, day 7 and day 30 or day of ICU discharge (whichever occurs first), day of ICU pneumonia, day 7 after ICU pneumonia and day 30 after ICU pneumonia.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

ICU patients in approximately 30 sites in 6-12 European countries will be selected based on eligibility criteria that are described below.

Inclusion will be based on S. aureus (SA) colonization status at ICU admission (ratio 1:1). These subjects will be followed through their ICU stay for assessment of the primary outcomes.

Criteria

Inclusion Criteria:

1. Participant is 18 years or older at the time of enrollment.
2. Participant is on mechanical ventilation at ICU admission, or is (expected to be) within 24 hours thereafter, based on investigator's judgment.
3. Expected stay in ICU is 48 hours or longer based on investigator's judgment.
4. SA colonization status is known within 72 hours after start of first episode of mechanical ventilation and according to the result, the patient qualifies for enrollment.
5. Written informed consent from subject / legally accepted representative within 72 hours after start of first episode of mechanical ventilation.

Exclusion Criteria:

1. Previous participation as a subject in the study cohort of this study.
2. Simultaneous participation of the subject in any preventive experimental study into anti-staphylococcus or anti-pseudomonas aeruginosa interventions.
3. Expected death (moribund status) within 48h, or ICU discharge of the participant within 24h, at the moment of informed consent.

Contacts and Locations

Locations

Netherlands

UMC Utrecht

Utrecht, Netherlands

Sponsors and Collaborators

Jan Kluytmans

MedImmune LLC

Universiteit Antwerpen

Investigators

• Principal Investigator: Jan A.J.W. Kluytmans, Prof.; UMC Utrecht

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paling FP, Troeman DPR, Wolkewitz M, Kalyani R, Prins DR, Weber S, Lammens C, Timbermont L, Goossens H, Malhotra-Kumar S, Sifakis F, Bonten MJM, Kluytmans JAJW. Rationale and design of ASPIRE-ICU: a prospective cohort study on the incidence and predictors of Staphylococcus aureus and Pseudomonas aeruginosa pneumonia in the ICU. BMC Infect Dis. 2017 Sep 25;17(1):643. doi: 10.1186/s12879-017-2739-4.

• Responsible Party: Jan Kluytmans, Professor, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT02413242
• Other Study ID Numbers: NL51762.041.14
• First Posted: April 9, 2015
• Last Update Posted: May 8, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Jan Kluytmans, UMC Utrecht:

S. aureus; P. aeruginosa; Colonization; Pneumonia; ICU

Additional relevant MeSH terms:

Pneumonia; Pseudomonas Infections; Healthcare-Associated Pneumonia; Pneumonia, Ventilator-Associated; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes