Evolution of Molecular Biomarkers in Acute Heart Failure Induced by Shock

NCT02141607 | Completed

• 2 other identifiers: FP7#602706602706
• Study Type: observational
• Target: 70
• Locations: 3 countries
• Sites: 3

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

Keywords

shock; heart failure; inflammation; biomarkers; cardiovascular instability; metabolic pathways; proteolysis

Outcome Measures

Primary Outcomes (1)

• Progression/occurrence of acute heart failure and changes in omics markers in acute phase of shock

  The clinical endpoint will be Acute Heart Failure (AHF), assessed by a pool of measures/estimates of cardiac function and filling pressures, based on cardiac output monitoring, inotropic drugs requirements, left and right ventricles assessment using echocardiography. The molecular biomarkers changes will be evaluated by means of proteomics, transcriptomics and metabolomics analysis of blood samples collected at the ICU admission and within 48hr after admission.

  within 48 hr after admission in ICU (acute phase of shock)

Secondary Outcomes (1)

• Progression/Occurence of Acute Heart Failure and changes in omics markers in survivors

  within 7 days after admission in ICU (patient stabilization)

Other Outcomes (1)

• Long term effects of AHF in survivors assessed by changes in omics markers

  at about 100 days from ICU admission and enrollment

Study Arms (4)

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

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

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.

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.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All the patients admitted to ICU

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shockomics Consortium: lead
• Seventh Framework Programme: collaborator

Study Sites (3)

Department of Intensive Care, Erasme University Hospital

Brussels, Belgium

Location

Servei de Medicina Intensiva, Hospital Universitari Mútua Terrassa

Barcelona, Spain

Location

Intensive Care Division, Geneva University Hospitals

Geneva, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 29112634 RESULT

• 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.

  PMID: 28851978 RESULT

• 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.

  PMID: 36867756 DERIVED

• 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.

  PMID: 31856860 DERIVED

• 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.

  PMID: 30336851 DERIVED

• 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.

  PMID: 26822963 DERIVED

• 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.

  PMID: 26736871 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum

MeSH Terms

Conditions

Shock; Heart Failure; Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Study Officials

• Giuseppe Baselli, MS

  Politecnico di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 19, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: September 1, 2017
• Last Updated: June 15, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); ES (1); CH (1)