Proadrenomedullin and Copeptin in Patients With Septic Shock (proADM)

Proadrenomedullin and Copeptin as Predictors of Vasopressor Requirements and Volume Resuscitation in Patients With Septic Shock

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock

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 Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41108
    • Jose Garnacho-Montero

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients with septic shock

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with septic shock; patients in septic shock admitted to the ICU

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Spanish Network for Research in Infectious Diseases
• Investigators: Principal Investigator: José Garnacho-Montero, MD, Hospital Universitario Virgen Macarena

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): March 11, 2021

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 2, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Septic Shock; Copeptin; Vasopressors; Proadrenomedullin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Endocrine System Diseases; Sepsis; Pituitary Diseases; Shock, Septic; Shock; Diabetes Insipidus
• Other Study ID Numbers: 0530-N-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO