InfectionNCT03931967
Proadrenomedullin and Microcirculation in Monitoring Organ Dysfunction in Patient With Infection
An observational study of Infection and Sepsis, run by Università Politecnica delle Marche at 1 site in Italy.
Trial summary
This study evaluates the association between plasmatic levels of Mid Regional Proadrenomedullin (MR-proADM) and the sublingual microcirculation in critical care patients admitted with infection, sepsis or septic shock. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Sepsis, Septic Shock
- What is being tested?
- MR-proADM
- How many people
- 21 participants
- Where
- 1 siteItaly
- Study dates
- 8 Nov 2018to 4 Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 20 patients with suspected infection, infection, sepsis or septic shock admitted to ICU
Who may be able to join
- Suspected Infection, Infection, Sepsis or Septic Shock in patient admitted in ICU from no more than 24 hours and which have previously monitored blood pressure and have a central venous catheter in place.
Who cannot join
- Age < 18 yo
- Length of stay in ICU > 24 hours;
- Length of stay in other hospital unit, ward or surgery > 48 hours;
- Refusal of informed consent;
- Conditions that do not allow the possibility of getting a monitoring of sublingual microcirculation (maxillofacial trauma, serious inability to jaw, copious blood loss or secretions from the mouth)
Trial locations and contacts
1 site in 1 country.
Italy1 site
AOU Ospedali Riuniti Ancona - Università Politecnica delle Marche
Ancona, 60126
About this study
Official title: Proadrenomedullin and Microcirculation in Monitoring Organ Dysfunction in Patient With Infection: Prospective Observational Study
This study evaluates the association between plasmatic levels of Mid Regional Proadrenomedullin (MR-proADM) and the sublingual microcirculation in critical care patients admitted with infection, sepsis or septic shock.
Read the detailed description
MR-proADM (Mid Region proAdrenomedullin) is a fragment of 48 amino-acids of ADM (Adrenomedullin), a protein belonging to the super-family of calcitonin-related peptides. MR-proADM is released in a 1:1 ratio with its native protein ADM. Blood levels of ADM are high in several conditions including infection, sepsis of septic shock. MR-proADM seems to be a promising marker for early diagnosis, prognosis and mortality in sepsis and it is also related to sepsis-induced organ failure.
The microcirculatory and endothelial damages represent two corner stones of the sepsis pathophysiology. They involved the loss of functional capillaries density and the loss of red blood cells deformability, the endothelial cell disfunction induced by sepsis, the induction of the apoptosis and necrosis, the alteration in the capillary permeability due to the loss of vasomotor tone and control. Moreover sepsis is characterised by the increased levels of adhesion molecules and the consequent interaction between neutrophils and endothelium, the fibrin deposition and the activation of the coagulation.
The aim of the study is to evaluate the correlation between the alteration in microcirculation and the levels of MR-proADM.
MFI (Microvascular Flow Index) is a qualitative measurement of microcirculation and the microcirculatory alterations during sepsis are crucial in the pathophysiology of this syndrome. It is related to prognosis and mortality in patient with sepsis in ICU (Intensive Care Unit)
Studying the relations between MFI and MR-proADM in the first five days of ICU stay could represent a good way to connect the pathophysiological background to a laboratory marker for an early diagnosis and for a measure of prognosis in patient with infections.
It is also important to compare the levels of MR-proADM with the other microcirculatory parameters (Total Vessel Density, Perfused Vessels Density, Percentage of Perfused Vessels, DeBacker score, Flow Heterogeneity index) and with the parameters of glycocalix and endothelial disfunction (Perfused Boundary Region and Endothelin-1)
When inclusion criteria are present and there are no exclusion criteria, patients will be enrolled for this five-days long study. Informed consent will be taken from the patient before enrollment or from the legal representative but when the neurological conditions do not allow
At the beginning of the study anthropometric data will be collected together with the main clinical and laboratory parameters (systolic, diastolic and mean arterial pressure, heart rate, mechanical ventilation parameters, blood gas parameters, vasoactive therapy, main parameters for renal, hepatic and haematological function, infectious condition and cultures).
Arterial blood samples will be collected and blood will be immediately centrifuged and plasma and serum samples will be stored at -80°C for the measurement of MR-proADM and Endothelin-1.
Moreover at the beginning of the study, the day after and the fifth days from the enrolment, the main microcirculatory parameters will be taken through Incident Dark Field Technology. Glycocheck Technology will be used to collect glycocalix conditions.
- Conditions
- Infection, Sepsis, Septic Shock
- Being tested
- MR-proADM
- Keywords
- Sepsis, Septic shock, Microcirculation, Glycocalix, Proadrenomedullin, Organ dysfunction, Critical Care, Intensive Care
- Medical subject headings
- Infections, Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR-proADMDiagnostic test
to evaluate the plasmatic level of MR-proADM and endothelin-1 in the first five days of ICU stay.
| Study group | Role | What they receive |
|---|---|---|
| MR-proADM | Not described Receives: Diagnostic Test: MR-proADM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Microvascular Flow Index (MFI)
Correlation between plasmatic value of MR-proADM and variation in Microvascular Flow Index (MFI) in patients admitted in ICU with suspected infection. MFI is detected in vivo by Incident Dark Field (IDF) Imaging at sublingual microcirculation. It represents the quality of blood flow at microcirculatory level.
Measured: Five days
Assessment of the concentration of Mid Regional Proadrenomedullin (MR-proADM)
Correlation between plasmatic value of MR-proADM and variation in Microvascular Flow Index (MFI) in patients admitted in ICU with suspected infection. Mid Regional Proadrenomedullin (MR-proADM, unity of measurement nmol/L) is measured through a specify immunoenzymatic assay. MR-proADM is a diagnostic and prognostic marker of infection and sepsis.
Measured: Five days
Secondary outcomes (7)
Cut-off for Microvascular Flow Index (MFI) based on Mid Regional Proadrenomedullin (MR-proADM) levels
Founding a MR-proADM cut-off which would be able to predict a variation in MFI in patients admitted in ICU with suspected infection.
Measured: Five days
Assessment of patient's mortality
Correlation between mortality (in percentage) and plasmatic levels of MR-proADM, based on MR-proADM clearance.
Measured: Five days
Assessment of new organ failure
Correlation between organ failures and MRproADM, based on daily calculation of Sequential Organ Failure Assessment Score(SOFA score, 0 best value up to 24 worst value).Score subscales:Respiratory(PaO2/FiO2 (mmHg)≥ 400,score 0,< 400,+1,< 300, +2,< 200 and mechanically ventilated,+3,< 100 and mechanically ventilated,+4);Nervous(Glasgow coma scale 15,score 0,13-14,+1,10-12 +2,6-9 and mechanically ventilated,score +3,<6,+4);Cardiovascular(Mean arterial pressure/vasopressors:MAP≥70 mmHg,score 0,MAP<70 mmHg,+1,dopamine≤5 µg/kg/min or dobutamine (any dose),+2,dopamine>5 µg/kg/min OR epinephrine≤0.1 µg/kg/min OR norepinephrine≤ 0.1µg/kg/min,+3,dopamine>15 µg/kg/min OR epinephrine>0.1µg/kg/min OR norepinephrine>0.1µg/kg,+4);Liver(Bilirubin(mg/dl)[μmol/L],< 1.2[< 20],score 0,1.2-1.9[20-32],+1,2.0-5.9[33-101], +2,6.0-11.9[102-204],+3,> 12.0[> 204],+4);Kidney(Creatinine (mg/dl)[μmol/L] < 1.2[< 110],score 0,1.2-1.9[110-170],+1,2.0-3.4[171-299],+2,3.5-4.9[300-440],+3,> 5.0[> 440], +4),Coagulation
Measured: Five days
Assessment of Procalcitonine (PCT)
Correlation between PCT (Unity of measurement, ng/ml) and MR-proADM as combined score for outcome measurement in term of mortality.
Measured: Five days
Assessment of other microcirculatory parameters in patient with sepsis or septic shock.
Correlation between plasmatic value of MR-proADM and variation in Perfused Vessels Density (PVD, unity of measure 1/mm), Percentage of Perfused Vessels (PPV, unity of measure %), Total Vessels Density (TVD, unity of measure mm/mm2), Flow Heterogeneity Index (FHI), DeBacker Score (unit of measure, 1/mm). The parameters are detected in vivo by Incident Dark Field (IDF) Imaging at sublingual microcirculation. MR-proADM is a diagnostic and prognostic marker of infection and sepsis.
Measured: Five days
Mid Regional Proadrenomedullin (MR-proADM) in patient with difference infectious condition.
Comparison of the MR-proADM blood concentration (nmol/L) in patient with suspected infection, infection, sepsis and septic shock.
Measured: Five days
Correlation between Mid Regional Proadrenomedullin (MR-proADM) and glycocalix and endothelial damage.
Association between plasmatic value of MR-proADM and variation in Perfused Boundary Region (PBR, the parameters is detected in vivo by Sidestream Dark Field (SDF) Imaging at sublingual microcirculation) and Endothelin-1. MR-proADM is a diagnostic and prognostic marker of infection and sepsis.
Measured: Five days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start8 Nov 2018
- Primary completion4 Jun 2019
- Study completion4 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Università Politecnica delle Marche
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Abele Donati, MD, Università Politecnica delle Marche
- Investigators
- Abele Donati, MD, PhD, Principal investigator, UNIVERSITA' POLITECNICA DELLE MARCHE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03931967
- Sponsor's protocol ID
- MicroMRproADM
- Status last verified
- Apr 2019
- First submitted
- 5 Mar 2019
- Last updated
- 18 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proadrenomedullin and Microcirculation in Monitoring Organ Dysfunction in Patient With Infection: Prospective Observational Study
- ClinicalTrials.gov ID
- NCT03931967
- Acronym / sponsor ID
- MicroMRproADM
- Conditions
- Infection, Sepsis, Septic Shock
- Keywords
- Sepsis, Septic shock, Microcirculation, Glycocalix, Proadrenomedullin, Organ dysfunction, Critical Care, Intensive Care
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Università Politecnica delle MarcheUniversity, hospital or other
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 4 Jun 2019 (actual)
- Study completion
- 4 Jun 2019 (actual)
- First posted
- 30 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the association between plasmatic levels of Mid Regional Proadrenomedullin (MR-proADM) and the sublingual microcirculation in critical care patients admitted with infection, sepsis or septic shock.
Detailed description
MR-proADM (Mid Region proAdrenomedullin) is a fragment of 48 amino-acids of ADM (Adrenomedullin), a protein belonging to the super-family of calcitonin-related peptides. MR-proADM is released in a 1:1 ratio with its native protein ADM. Blood levels of ADM are high in several conditions including infection, sepsis of septic shock. MR-proADM seems to be a promising marker for early diagnosis, prognosis and mortality in sepsis and it is also related to sepsis-induced organ failure.
The microcirculatory and endothelial damages represent two corner stones of the sepsis pathophysiology. They involved the loss of functional capillaries density and the loss of red blood cells deformability, the endothelial cell disfunction induced by sepsis, the induction of the apoptosis and necrosis, the alteration in the capillary permeability due to the loss of vasomotor tone and control. Moreover sepsis is characterised by the increased levels of adhesion molecules and the consequent interaction between neutrophils and endothelium, the fibrin deposition and the activation of the coagulation.
The aim of the study is to evaluate the correlation between the alteration in microcirculation and the levels of MR-proADM.
MFI (Microvascular Flow Index) is a qualitative measurement of microcirculation and the microcirculatory alterations during sepsis are crucial in the pathophysiology of this syndrome. It is related to prognosis and mortality in patient with sepsis in ICU (Intensive Care Unit)
Studying the relations between MFI and MR-proADM in the first five days of ICU stay could represent a good way to connect the pathophysiological background to a laboratory marker for an early diagnosis and for a measure of prognosis in patient with infections.
It is also important to compare the levels of MR-proADM with the other microcirculatory parameters (Total Vessel Density, Perfused Vessels Density, Percentage of Perfused Vessels, DeBacker score, Flow Heterogeneity index) and with the parameters of glycocalix and endothelial disfunction (Perfused Boundary Region and Endothelin-1)
When inclusion criteria are present and there are no exclusion criteria, patients will be enrolled for this five-days long study. Informed consent will be taken from the patient before enrollment or from the legal representative but when the neurological conditions do not allow
At the beginning of the study anthropometric data will be collected together with the main clinical and laboratory parameters (systolic, diastolic and mean arterial pressure, heart rate, mechanical ventilation parameters, blood gas parameters, vasoactive therapy, main parameters for renal, hepatic and haematological function, infectious condition and cultures).
Arterial blood samples will be collected and blood will be immediately centrifuged and plasma and serum samples will be stored at -80°C for the measurement of MR-proADM and Endothelin-1.
Moreover at the beginning of the study, the day after and the fifth days from the enrolment, the main microcirculatory parameters will be taken through Incident Dark Field Technology. Glycocheck Technology will be used to collect glycocalix conditions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MR-proADM | – | Diagnostic Test: MR-proADM |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 20 patients with suspected infection, infection, sepsis or septic shock admitted to ICU
Key inclusion criteria (1 listed)
- Suspected Infection, Infection, Sepsis or Septic Shock in patient admitted in ICU from no more than 24 hours and which have previously monitored blood pressure and have a central venous catheter in place.
Key exclusion criteria (5 listed)
- Age < 18 yo
- Length of stay in ICU > 24 hours;
- Length of stay in other hospital unit, ward or surgery > 48 hours;
- Refusal of informed consent;
- Conditions that do not allow the possibility of getting a monitoring of sublingual microcirculation (maxillofacial trauma, serious inability to jaw, copious blood loss or secretions from the mouth)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MR-proADMto evaluate the plasmatic level of MR-proADM and endothelin-1 in the first five days of ICU stay. | Diagnostic test | MR-proADM |
Primary outcome
Assessment of Microvascular Flow Index (MFI)
Time frame: Five days
Correlation between plasmatic value of MR-proADM and variation in Microvascular Flow Index (MFI) in patients admitted in ICU with suspected infection. MFI is detected in vivo by Incident Dark Field (IDF) Imaging at sublingual microcirculation. It represents the quality of blood flow at microcirculatory level.
Assessment of the concentration of Mid Regional Proadrenomedullin (MR-proADM)
Time frame: Five days
Correlation between plasmatic value of MR-proADM and variation in Microvascular Flow Index (MFI) in patients admitted in ICU with suspected infection. Mid Regional Proadrenomedullin (MR-proADM, unity of measurement nmol/L) is measured through a specify immunoenzymatic assay. MR-proADM is a diagnostic and prognostic marker of infection and sepsis.
7 secondary outcomes
Cut-off for Microvascular Flow Index (MFI) based on Mid Regional Proadrenomedullin (MR-proADM) levels
Time frame: Five days
Assessment of patient's mortality
Time frame: Five days
Assessment of new organ failure
Time frame: Five days
Assessment of Procalcitonine (PCT)
Time frame: Five days
Assessment of other microcirculatory parameters in patient with sepsis or septic shock.
Time frame: Five days
Mid Regional Proadrenomedullin (MR-proADM) in patient with difference infectious condition.
Time frame: Five days
Correlation between Mid Regional Proadrenomedullin (MR-proADM) and glycocalix and endothelial damage.
Time frame: Five days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abele Donati, MD, PhD principal investigator
UNIVERSITA' POLITECNICA DELLE MARCHE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infection and Sepsis, run by Università Politecnica delle Marche at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Microvascular Flow Index (MFI) (time frame: Five days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2019.