Clinical trial NCT03651635: MR-proADM and CT-proET-1 During ICU Treatment
Official title: To Assess and Validate the Use of MR-proADM and the CT-proET-1/MR-proADM Ratio as Prognostic Markers During the First 7 Days of ICU Treat-ment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Phase Biomarkers
Medical ICU Admitted Patients
Keywords: ICU
Biomarkers
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: ThermoFisher Scientific Brahms Biomarkers France
First posted: 2018-08-29
Enrollment: 533
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: All patients admitted to the medical intensive care unit of the University hospital of Zurich during the recruitment period

Brief summary: This pilot-study will be a prospective, single-centre, observational study including 100 critically ill patients consecutively admitted to the medical intensive care unit (ICU) of the University hospital of Zurich, Switzerland, to assess and validate the use of MR-proADM and the CT-proET1/MR-proADM-ratio as prognostic markers in critically ill patients.

Detailed description: This pilot-study will be a prospective, single-centre, observational study including 100 critically ill patients consecutively admitted to the medical intensive care unit (ICU) of the University hospital of Zurich, Switzerland, to assess and validate the use of MR-proADM and the CT-proET1/MR-proADM-ratio as prognostic markers in critically ill patients. After obtaining informed consent of the patient or approval of a legal representative and meeting of the inclusion, as well as missing exclusion criteria the patients will be enrolled.

At study enrolment patient health status will be assessed by health related diagnosis and the Charlson comorbidity index. This information is obtained routinely in every patient in our ICU. The Charlson comorbidity index is calculated based on the medical history of the patient. The values of MR-proADM and CT-proET-1 will be measured daily over the first 7 days of the ICU stay. If a patient is discharged before day 7, no further measurements will be performed. The blood samples will be collected together with the routine blood check on admission, as well as each morning. Clinical evaluation of the patients will take place each morning including the evaluation of the hemodynamics, organ dysfunction, microcirculation and the need for vasopressors.

The severity of illness of the patient will be assessed using the SAPS II score and the SOFA score. SAPS-II reflects the physiological status of the patient within the first 24 hours (admission severity) and the SOFA score the number of failing organs (respiration, coagulation, liver, cardiovascular, CNS, renal). The SAPS-II will be assessed on Visit 3 and the SOFA daily using the information obtained during the routine clinical examination and the laboratory results of the day. SAPS II and SOFA scores are part of the routine assessment of all our patients in the ICU and are used as quality indicators.

The status of the microcirculation is assessed using clinical signs (mottling score, capillary refill time and sublingual microcirculation functional status) and laboratory parameters reflecting the degree of tissue oxygen extraction such as SaO2-SvO2 gap, Pv-aCO2 gap and the arterial lactate concentration. All these parameters are delivered by the blood gas analyser located in the ICU from an arterial and a venous blood sample of 1.5 ml each drawn via the arterial and central venous line respectively. These catheters and blood samples are part of the routine hemo-dynamic monitoring and assessment of the critically ill patient in our ICU.

The patients' survival status will be assessed on day 7 and day 28 after study enrolment. In addition, ICU and hospital mortality are recorded. If the patient is still in the hospital on day 28, survival data will be taken from the medical record. In the case the patient is dismissed from the hospital the study team will contact him by phone call. If he is not reachable (documented attempts) the study team will contact his general practitioner. To be in line with data protection requirements the patient gives the consent to contact the general practitioner in the informed consent form. No other information than the survival status will be collected at this stage. Data collection for the study ends 28 (± 3 days) days after enrolment.

Eligibility criteria: Inclusion Criteria:

* All patients admitted to the medical intensive care unit of the University hospital of Zurich during the recruitment period
* Male and female participants ≥ 18 years
* Written informed consent by the participant after information about the research project or if the patient is incapable of giving informed consent, a legal representative has confirmed the presumed will of the participant (according Art. 15 KlinV emergency patients)

Exclusion Criteria:

* Inability of the conscious patients to follow the experimental procedure, e.g. because of insufficient language skills (German), mental illness, dementia etc.
* Pregnancy
* Participation in ongoing clinical trials of other departments of the University Hospital Zurich

Primary outcomes:
measure: Area under the concentration-time curve (AUROCCs) for MR-proADM
timeFrame: 7 days
measure: Area under the concentration-time curve (AUROCCs) for the CT-proET-1/MR-proADM-ratio
timeFrame: 7 days
Secondary outcomes:
measure: Correlation between area under the concentration-time curve for MR-proADM and microcirculation status
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for the CT-proET1/MR-proADM-ratio and microcirculation status
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for MR-proADM and cardiac biomarkers
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for the CT-proET1/MR-proADM-ratio and cardiac biomarkers
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for MR-proADM and biomarkers of inflammation
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for the CT-proET-1/MR-proADM-ratio and biomarkers of inflammation
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for MR-proADM and renal dysfunction
timeFrame: 7 days
measure: Correlation between area under the concentration-time curve for the CT-proET1/MR-proADM-ratio and renal dysfunction
timeFrame: 7 days
measure: Admission plasma levels of MR-proADM as a predictor of multiorgan dysfunction
timeFrame: 7 days
measure: Admission plasma levels of the CT-proET1/MR-proADM-ratio as a predictor of multiorgan dysfunction
timeFrame: 7 days
measure: AUROCCs for MR-proADM during the first 7 days of ICU treatment as predictors of mortality
timeFrame: 28 days
measure: AUROCCs for the MR-proADM/CT-proET-1-ratio during the first 7 days of ICU treatment as predictors of mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Medical intensive care unit
state: ZH
Study officials:
affiliation: University Zürich/ University Hospital Zürich
name: Marco Maggiorini, MD
role: PRINCIPAL_INVESTIGATOR
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