Proadrenomedullin and Copeptin in Patients With Septic Shock

Completed

• Conditions: Septic Shock

• Registration Number: NCT03104933
• Lead Sponsor: Spanish Network for Research in Infectious Diseases

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.

Study Timeline

• Study Start: 2016-07-01
• Study First Submitted: 2017-03-20
• Study First Submitted QC: 2017-04-03
• Study First Posted: 2017-04-07
• Status Verified: 2019-06
• Primary Completion: 2019-09-30
• Study Completion: 2021-03-11
• Last Update Submitted: 2021-03-30
• Last Update Posted: 2021-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Levels of proADM as predictor of vasopressor requirements	the first 72 hours.	measured by index inotropic and vasopressor dependency ratio) and fluid requirement
Levels o Copeptin as predictor of vasopressor requirements (measured by index inotropic and vasopressor dependency ratio) and fluid requirement	the first 72 hours.	measured by index inotropic and vasopressor dependency ratio) and fluid requirement

Secondary Outcome Measures

Name	Time	Method
Levels of proADM and Copeptin as predictor of 28-day mortality rate	28 days	Mortality
Levels of proADM and Copeptin as predictors of lactate clearance	6 hours	Lactate clearance
Levels of proADM and Copeptin as predictors of organ dysfunction	28 days	SOFA scale

Trial Locations

Locations (1)

José Garnacho-Montero; 🇪🇸 Seville, Spain