Evolution of Molecular Biomarkers in Acute Heart Failure Induced by Shock

NCT ID: NCT02141607

Last Updated: 2018-06-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2017-09-30

Brief Summary

The relationship between shock, ischemia and reperfusion (I/R) injury, hemodynamic instability, systemic inflammatory response syndrome and multiorgan failure has been extensively investigated, but there is no consensus on the trigger mechanisms of tissue injury at the molecular level.

Current therapies are targeted to reduce symptoms of shock and multiorgan damage but they are unable to act at the "beginning of the cascade", because of the lack of a model explaining the molecular basis of shock induced tissue injury and ensuing organ damage.

The present observational study is aimed at identifying the molecular triggers of acute heart failure (HF) induced by shock and to identify inflammatory mediators and markers that are activated in shock, with a particular emphasis on the role of uncontrolled proteolytic activity.

Conditions

Acute Heart Failure; Shock

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Hemorrhagic Shock

Hypovolemic shock characterized by:

• Hypotension: systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation.
• Rapid loss of significant amount of blood
• Lactate levels ≥ 2 mmol/L

No interventions assigned to this group

Cardiogenic shock

State of inadequate circulation of blood because of ventricular failure due to acute cardiac conditions, concomitant presence of:

• Hypotension: systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation.
• Need for a continuous infusion of inotropic drugs
• Cardiac Index <2.2 L/min/m2 or use of inotropic drugs (dobutamine/isoprenaline/phosphodiesterase inhibitors or levosimendan)
• Signs of reduced heart function
• Cardiac overload or altered left/right ventricular function

No interventions assigned to this group

Septic shock

Septic shock is defined as sepsis-induced hypotension, defined as systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation.

Only community medical acquired sepsis with a sepsis onset within 48 hours from hospital admission (i.e. different from nosocomial infection).

Lactate levels ≥ 2mmol/L.

No interventions assigned to this group

control group

The control group will consist on:

1. 5 healthy blood donors: serving only for the purposes of obtaining reference values for proteomics analysis

2. a cohort of 20 patients hospitalized for sepsis OR cardiac syndromes not developing shock: will be recruited from patients admitted to the hospital during the study period. The clinical status of the patients will be assessed during hospitalization to ascertain shock and AHF development. Shock development will be an exclusion criteria.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• For patients in septic shock, Severity: SOFA score > 5
• For patients in cardiogenic shock, Severity: SOFA score > 5
• First blood sample available within 16 hours from admission to the ICU.
• Only community medical acquired septic shock. We include patients with shock symptoms and shock diagnosis occurring within the first 48 hours from hospital admission
• Informed Consent available

Exclusion Criteria

• Risk of rapidly fatal illness and death within 24 hours
• Patients already enrolled in other interventional studies
• N > 4 units of red blood cells transfused
• Patients treated with plasma or whole blood
• Active hematological malignancy
• Metastatic cancer
• Immunodepression, including transplant patients: HIV+, constitutive immune system deficiency, immunosuppressive therapy, systemic corticosteroids (aerosols allowed)
• Patients with pre-existing end stage renal disease needing renal replacement therapy (RRT). The introduction of continuous veno-venous hemofiltration (CVVH), from the day of admission onward is allowed.
• Cardiac surgery patients
• Cirrhosis Child C

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seventh Framework Programme

OTHER

Sponsor Role: collaborator

Shockomics Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Baselli, MS

Role: PRINCIPAL_INVESTIGATOR

Politecnico di Milano

Locations

Department of Intensive Care, Erasme University Hospital

Brussels, , Belgium

Servei de Medicina Intensiva, Hospital Universitari Mútua Terrassa

Barcelona, , Spain

Intensive Care Division, Geneva University Hospitals

Geneva, , Switzerland

Countries

Belgium; Spain; Switzerland

References

Carrara M, Bollen Pinto B, Baselli G, Bendjelid K, Ferrario M. Baroreflex Sensitivity and Blood Pressure Variability can Help in Understanding the Different Response to Therapy During Acute Phase of Septic Shock. Shock. 2018 Jul;50(1):78-86. doi: 10.1097/SHK.0000000000001046.

Reference Type: RESULT

PMID: 29112634 (View on PubMed)

Cambiaghi A, Pinto BB, Brunelli L, Falcetta F, Aletti F, Bendjelid K, Pastorelli R, Ferrario M. Characterization of a metabolomic profile associated with responsiveness to therapy in the acute phase of septic shock. Sci Rep. 2017 Aug 29;7(1):9748. doi: 10.1038/s41598-017-09619-x.

Reference Type: RESULT

PMID: 28851978 (View on PubMed)

Maegele M, Aletti F, Efron PA, Relja B, Orfanos SE. NEW INSIGHTS INTO THE PATHOPHYSIOLOGY OF TRAUMA AND HEMORRHAGE. Shock. 2023 Mar 1;59(3S Suppl 1):6-9. doi: 10.1097/SHK.0000000000001954. Epub 2022 Jul 24.

Reference Type: DERIVED

PMID: 36867756 (View on PubMed)

Braga D, Barcella M, Herpain A, Aletti F, Kistler EB, Bollen Pinto B, Bendjelid K, Barlassina C. A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock. Crit Care. 2019 Dec 19;23(1):414. doi: 10.1186/s13054-019-2670-8.

Reference Type: DERIVED

PMID: 31856860 (View on PubMed)

Bauza-Martinez J, Aletti F, Pinto BB, Ribas V, Odena MA, Diaz R, Romay E, Ferrer R, Kistler EB, Tedeschi G, Schmid-Schonbein GW, Herpain A, Bendjelid K, de Oliveira E. Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality. Br J Anaesth. 2018 Nov;121(5):1065-1074. doi: 10.1016/j.bja.2018.05.072. Epub 2018 Jul 26.

Reference Type: DERIVED

PMID: 30336851 (View on PubMed)

Aletti F, Conti C, Ferrario M, Ribas V, Bollen Pinto B, Herpain A, Post E, Romay Medina E, Barlassina C, de Oliveira E, Pastorelli R, Tedeschi G, Ristagno G, Taccone FS, Schmid-Schonbein GW, Ferrer R, De Backer D, Bendjelid K, Baselli G. ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock. Scand J Trauma Resusc Emerg Med. 2016 Jan 28;24:9. doi: 10.1186/s13049-016-0197-4.

Reference Type: DERIVED

PMID: 26822963 (View on PubMed)

Carrara M, Baselli G, Ferrario M. Mortality prediction in septic shock patients: Towards new personalized models in critical care. Annu Int Conf IEEE Eng Med Biol Soc. 2015 Aug;2015:2792-5. doi: 10.1109/EMBC.2015.7318971.

Reference Type: DERIVED

PMID: 26736871 (View on PubMed)

Other Identifiers

602706

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

FP7#602706

Identifier Type: -

Identifier Source: org_study_id