Evolution of Molecular Biomarkers in Acute Heart Failure Induced by Shock (Shockomics)

Shockomics Consortium

Status: Completed

Conditions: Shock; Acute Heart Failure

Study type: Observational

Funder types: Other; NETWORK

Identifiers

NCT02141607

FP7#602706

602706 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

70 participants in 4 patient groups

Hemorrhagic Shock

Description:

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

Cardiogenic shock

Description:

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

Septic shock

Description:

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.

control group

Description:

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.