Clinical trial NCT03104933: Proadrenomedullin and Copeptin in Patients With Septic Shock
Official title: Proadrenomedullin and Copeptin as Predictors of Vasopressor Requirements and Volume Resuscitation in Patients With Septic Shock
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Septic Shock
Keywords: Proadrenomedullin
Copeptin
Vasopressors
Septic Shock
Lead sponsor: Spanish Network for Research in Infectious Diseases
Sponsor class: OTHER
First posted: 2017-04-07
Enrollment: 103
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: Critically ill patients with septic shock

Brief summary: This study evaluates the usefulness of pro-adrenomedullin (precursor of a vasodilatory peptide involved in septic shock pathogenesis) and copeptin (a stable peptide of the arginine vasopressin precursor) to predict, at the moment of septic shock diagnosis or their changes at 6 hours, the vasopressor requirements (measured by inotropic index and vasopressor dependency ratio) and volume requirement for resuscitation.

Detailed description: Physiologically, adrenomedullin has a potent and prolonged vasodilatory effect. In both experimental animals and humans, the intravenous administration of ADM induces a marked and prolonged hypotension. Serum ADM levels are elevated in patients with septic shock. In fact, ADM seems to be one of the main mediators involved in hypotension that these patients present.

ADM is not stable in plasma due to its short half-life and rapid binding to receptors. ADM levels can be measured indirectly by determining proadrenomedullin (proADM) which is a more stable molecule and whose levels are reflected in the plasma of ADM.

Copeptin is released primarily in response to changes in serum osmolarity or blood volume by increasing peripheral vascular resistance and blood pressure.

Copeptin is elevated in patients with shock of different etiologies such as hemorrhagic shock or septic shock.

It is not defined in what situations and at what moment an invasive monitoring of the cardiac output and the different hemodynamic variables that reflect the preload and afterload in patients with septic shock should be performed. In fact, there is great variability in the management and treatment of patients with sepsis and septic shock, which includes the selection of patients who require invasive monitoring and the time of onset.

Having a biomarker or the combination of biomarkers that allow early determination of which patients will evolve poorly with the development of a shock that requires volume in large quantities and high doses of vasopressors will allow identifying a subgroup of patients that should be performed early hemodynamic monitoring and intensify medical treatment to try to reverse these severe hemodynamic changes.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years
* Diagnosis of septic shock
* Obtaining written informed consent.

Exclusion Criteria:

* Initial dose of norepinephrine at ICU admission ≥ 0.6 mg / kg / min.
* Acute myocardial infarction in the previous month.
* History of pituitary surgery.
* Pregnancy.

Primary outcomes:
measure: Levels of proADM as predictor of vasopressor requirements
timeFrame: the first 72 hours.
measure: Levels o Copeptin as predictor of vasopressor requirements (measured by index inotropic and vasopressor dependency ratio) and fluid requirement
timeFrame: the first 72 hours.
Secondary outcomes:
measure: Levels of proADM and Copeptin as predictors of organ dysfunction
timeFrame: 28 days
measure: Levels of proADM and Copeptin as predictor of 28-day mortality rate
timeFrame: 28 days
measure: Levels of proADM and Copeptin as predictors of lactate clearance
timeFrame: 6 hours
Other outcomes:
Locations:
city: Seville
country: Spain
facility: José Garnacho-Montero
Study officials:
affiliation: Hospital Universitario Virgen Macarena
name: José Garnacho-Montero, MD
role: PRINCIPAL_INVESTIGATOR
References: