Ignite Creation Date:
2024-05-06 @ 9:35 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03014063
Status:
COMPLETED
Last Update Posted:
2019-01-31
First Post:
2017-01-04
Brief Title:
Vasopressin Plasma Concentrations in Patients Receiving Exogenous Vasopressin Infusion for Septic Shock
Sponsor:
The Cleveland Clinic
Organization:
The Cleveland Clinic
Study Overview
Official Title:
Vasopressin Plasma Concentrations in Responders and Non-responders to Exogenous Vasopressin Infusion in Patients With Septic Shock
Status:
COMPLETED
Status Verified Date:
2019-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a prospective observational cohort trial evaluating a single plasma vasopressin concentration in patients receiving exogenous adjunctive vasopressin for septic shock The trial is designed to determine whether plasma vasopressin concentration influences the likelihood of hemodynamic response to exogenous vasopressin therapy
Detailed Description:
Vasopressin is an endogenous hormone that decreases serum osmolarity and increases blood pressure As a part of the stress response to hypotension vasopressin is released from the posterior pituitary and leads to vasoconstriction through agonism of the vascular vasopressin V1 receptor In patients with septic shock endogenous vasopressin levels are initially elevated but quickly fall to levels at or below those of normal physiology 14-36pgmL because of the depletion of endogenous store Sharshar et al evaluated two sets of patients with septic shock one of which was evaluated earlier in the septic shock course 36 23 hours n18 and one evaluated at a later time from shock onset mean 387 284 hours n44 The group of patients evaluated earlier in their septic shock course were more likely than patients evaluated later to have elevated 36 pgmL plasma vasopressin levels 889 vs 386 respectively Similarly a case series evaluated single vasopressin levels in three patients with septic shock one of whom was in the first day of shock onset and two of whom were in the fifth and sixth day of shock onset The patient in the earlier stages of septic shock had a plasma vasopressin level that was increased 16pgmL while the two patients in the later stages of septic shock had decreased plasma vasopressin levels 16 and 18pgmL The exact timing of when patients transition from having elevated endogenous vasopressin levels to having normal levels of vasopressin is currently unclear In a clinical trial enrolling patients within the first 12 hours of shock onset median endogenous vasopressin levels were 35 pgmL interquartile range 18 53 pgmL n54 Some have even hypothesized that vasopressin levels rise before clinical hypotension is apparent and the decline in vasopressin levels is associated with the onset of apparent hypotension Further complicating this issue endogenous vasopressin levels have been shown to be lower in patients with septic shock compared to other shock etiologies such cardiogenic shock 31 1pgmL in patients with septic shock vs 227 22pgmL in patients with cardiogenic shock p0001 The etiology of this discrepancy in endogenous vasopressin response by shock type is unclear but a relative deficiency of vasopressin is theorized to exist in patients with septic shock
In light of these findings exogenous arginine vasopressin AVP has been added to exogenous catecholamines to increase mean arterial pressure MAP and to decrease catecholamine requirements in patients with vasodilatory shock The use of AVP for these purposes in patients with septic shock is in keeping with the Surviving Sepsis Campaign Guidelines In the Vasopressin and Septic Shock Trial VASST low-dose AVP was infused at a rate of 001-003 unitsmin in combination with norepinephrine to achieve a goal MAP of 65-75mmHg Plasma vasopressin levels in patients receiving AVP were elevated at 6 683pgmL and 24 hours 905pgmL in comparison to patients not receiving AVP 30pgmL at baseline with no significant change at 6 or 24 hours Association of plasma vasopressin levels with hemodynamic response to AVP though was not evaluated in VASST
Concomitant corticosteroid use has been observed to decrease the total dose of administered AVP to increase the proportion of patients alive and free of vasopressors at day 7 to increase plasma vasopressin concentrations by 33 at 6 hours and 67 at 24 hours and to lead to lower 28- and 90-day mortality 359 vs 447 p003 and 425 vs 555 p001 respectively than in those that received AVP alone These findings generated the hypothesis that concomitant administration of AVP and corticosteroids results in increased plasma vasopressin levels versus AVP administration alone leading to positive clinical outcomes in septic shock Furthering the hypothesis that plasma vasopressin levels may influence outcomes in septic shock genetic differences in leucylcystinyl aminopeptidase the primary vasopressin metabolic enzyme have been associated with more rapid vasopressin clearance lower plasma vasopressin levels and increased mortality in patients with septic shock However a study evaluating vasopressin plasma concentrations in patients with multiple shock types not administered exogenous AVP observed higher vasopressin concentrations in those with hemodynamic dysfunction than in those without mean 141 26 vs 87 108pgmL respectively regardless of shock type This suggests that plasma vasopressin concentration may not directly correlate with MAP
The impact of body mass which may influence vasopressin levels when fixed-dose AVP is administered on hemodynamic response to AVP has been inconsistent Studies have observed a negative correlation between BMI and change in MAP at 6 hours and a correlation between increasing weight-adjusted AVP dose and reduction in catecholamine requirements suggesting that hemodynamic response to AVP is associated with body mass In contrast a third study observed no association between BMI and AVP dose required to meet goal MAP when AVP was administered as the sole vasopressor Finally a fourth found an inverse correlation between BMI and APACHE II-adjusted 28-day mortality regardless of the fact that overweight and obese patients received less weight-adjusted vasopressin than underweight or normal weight patients This suggests that while BMI may impact plasma vasopressin concentration the change in vasopressin concentration may not have an impact on clinical outcomes
Recently a retrospective study was completed at the Cleveland Clinic to evaluate predictors of hemodynamic response to fixed-dose AVP in patients with septic shock Patients were considered to be responders to AVP if a decrease in catecholamine dose was achieved with MAP65mmHg at 6 hours The overall response rate to fixed-dose vasopressin was 454 Within this study only admission to surgical or neurosciences intensive care units ICU vs medical ICU and lower lactate level were associated with increasing chance of response to AVP OR 171 95 CI 1175-2463 p00049 and OR 0925 95 CI 0887-0965 p00003 respectively on logistic regression Factors previously found to impact vasopressin levels such as concomitant use of corticosteroids were not associated with hemodynamic response However plasma vasopressin levels were not evaluated in this retrospective study
The relationship between plasma vasopressin concentration and hemodynamic response in patients receiving AVP is unclear While concomitant corticosteroids have been observed to increase plasma vasopressin concentrations corticosteroids themselves have been shown to shorten time in septic shock possibly confounding any relationship between plasma vasopressin concentration and hemodynamic response in patients receiving both agents As previously mentioned data correlating body mass with hemodynamic response have been inconsistent but vasopressin levels in patients receiving fixed dose AVP seem to be lower in patients with higher body mass The recent study at the Cleveland Clinic found no association between factors associated with increased plasma vasopressin level and hemodynamic response Together these data call into question the idea of a dose-response relationship between plasma vasopressin concentration and hemodynamic response This study seeks to prospectively evaluate whether plasma vasopressin levels are associated with improved rates of hemodynamic response to fixed-dose AVP therapy in patients with septic shock
In light of these findings exogenous arginine vasopressin AVP has been added to exogenous catecholamines to increase mean arterial pressure MAP and to decrease catecholamine requirements in patients with vasodilatory shock The use of AVP for these purposes in patients with septic shock is in keeping with the Surviving Sepsis Campaign Guidelines In the Vasopressin and Septic Shock Trial VASST low-dose AVP was infused at a rate of 001-003 unitsmin in combination with norepinephrine to achieve a goal MAP of 65-75mmHg Plasma vasopressin levels in patients receiving AVP were elevated at 6 683pgmL and 24 hours 905pgmL in comparison to patients not receiving AVP 30pgmL at baseline with no significant change at 6 or 24 hours Association of plasma vasopressin levels with hemodynamic response to AVP though was not evaluated in VASST
Concomitant corticosteroid use has been observed to decrease the total dose of administered AVP to increase the proportion of patients alive and free of vasopressors at day 7 to increase plasma vasopressin concentrations by 33 at 6 hours and 67 at 24 hours and to lead to lower 28- and 90-day mortality 359 vs 447 p003 and 425 vs 555 p001 respectively than in those that received AVP alone These findings generated the hypothesis that concomitant administration of AVP and corticosteroids results in increased plasma vasopressin levels versus AVP administration alone leading to positive clinical outcomes in septic shock Furthering the hypothesis that plasma vasopressin levels may influence outcomes in septic shock genetic differences in leucylcystinyl aminopeptidase the primary vasopressin metabolic enzyme have been associated with more rapid vasopressin clearance lower plasma vasopressin levels and increased mortality in patients with septic shock However a study evaluating vasopressin plasma concentrations in patients with multiple shock types not administered exogenous AVP observed higher vasopressin concentrations in those with hemodynamic dysfunction than in those without mean 141 26 vs 87 108pgmL respectively regardless of shock type This suggests that plasma vasopressin concentration may not directly correlate with MAP
The impact of body mass which may influence vasopressin levels when fixed-dose AVP is administered on hemodynamic response to AVP has been inconsistent Studies have observed a negative correlation between BMI and change in MAP at 6 hours and a correlation between increasing weight-adjusted AVP dose and reduction in catecholamine requirements suggesting that hemodynamic response to AVP is associated with body mass In contrast a third study observed no association between BMI and AVP dose required to meet goal MAP when AVP was administered as the sole vasopressor Finally a fourth found an inverse correlation between BMI and APACHE II-adjusted 28-day mortality regardless of the fact that overweight and obese patients received less weight-adjusted vasopressin than underweight or normal weight patients This suggests that while BMI may impact plasma vasopressin concentration the change in vasopressin concentration may not have an impact on clinical outcomes
Recently a retrospective study was completed at the Cleveland Clinic to evaluate predictors of hemodynamic response to fixed-dose AVP in patients with septic shock Patients were considered to be responders to AVP if a decrease in catecholamine dose was achieved with MAP65mmHg at 6 hours The overall response rate to fixed-dose vasopressin was 454 Within this study only admission to surgical or neurosciences intensive care units ICU vs medical ICU and lower lactate level were associated with increasing chance of response to AVP OR 171 95 CI 1175-2463 p00049 and OR 0925 95 CI 0887-0965 p00003 respectively on logistic regression Factors previously found to impact vasopressin levels such as concomitant use of corticosteroids were not associated with hemodynamic response However plasma vasopressin levels were not evaluated in this retrospective study
The relationship between plasma vasopressin concentration and hemodynamic response in patients receiving AVP is unclear While concomitant corticosteroids have been observed to increase plasma vasopressin concentrations corticosteroids themselves have been shown to shorten time in septic shock possibly confounding any relationship between plasma vasopressin concentration and hemodynamic response in patients receiving both agents As previously mentioned data correlating body mass with hemodynamic response have been inconsistent but vasopressin levels in patients receiving fixed dose AVP seem to be lower in patients with higher body mass The recent study at the Cleveland Clinic found no association between factors associated with increased plasma vasopressin level and hemodynamic response Together these data call into question the idea of a dose-response relationship between plasma vasopressin concentration and hemodynamic response This study seeks to prospectively evaluate whether plasma vasopressin levels are associated with improved rates of hemodynamic response to fixed-dose AVP therapy in patients with septic shock
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None