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Effects of Paroxetine on Cardiovascular Function in Septic Patients

Phase 2
Recruiting
Conditions
Sepsis
Septic Shock
Interventions
Registration Number
NCT05725837
Lead Sponsor
Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude
Brief Summary

It is known that septic shock is characterized by arterial hypotension, decreased peripheral vascular resistance and hyporeactivity to vasoconstrictor agents, with NO being an important mediator of this organ dysfunction. Data in the literature have shown that hyporeactivity to catecholamines is associated with a decrease in the density of α and ß receptors in the aorta and heart, respectively, as well as an increase in GRK2 levels and that NO contributes to the increase of this kinase in sepsis .

Based on this, it is hypothesized that cardiac dysfunction and decreased peripheral vascular resistance observed in sepsis may result from an increase in GRK2 activity and/or expression and its inhibition may be a relevant therapeutic target in septic shock patients. Based on this line, a measurable clinical benefit of paroxetine through the regulation of GRK2 expression in patients with septic shock is postulated.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
92
Inclusion Criteria
  • Patient over 18 years of age;
  • Patient diagnosed with septic shock for less than 48 hours and using a minimum dose of noradrenaline (0.01 mcg/kg/min);
  • Patients and/or legal guardians who consented to participate in the study through the free and informed consent term before randomization.
Exclusion Criteria
  • Pregnant women;
  • Patients with inability to use the gastrointestinal tract;
  • Patients with known intolerance to paroxetine and/or fluoxetine;
  • Patients on concomitant use of medications that may potentiate the occurrence of serotonin syndrome (tramadol, citalopram, escitalopram, sertraline, desvenlafaxine, venlafaxine, duloxetine, sibutramine, bupropion, amitriptyline, nortriptyline, lithium);
  • Patients in end-of-life care or with an expected survival of less than 24 hours at the time of eligibility

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboParoxetine40mg, single dose a day, by mouth or enteric tube
ParoxetineParoxetine40mg, single dose a day, by mouth or enteric tube
Primary Outcome Measures
NameTimeMethod
Time to vasopressor discontinuation28 days of enrollment

Discontinuation of all vasopressors for at least 48 consecutive hours

Secondary Outcome Measures
NameTimeMethod
Mortality during ICU stay90 daus

Mortality in the ICU

Total sequential organ failure assessment score score variation 24 to 120 hours after randomization120 hours

Variation of the total sequential organ failure assessment score score between baseline daily until 120 hours later. Total sequential organ failure assessment score varies between 0 and +24 points, higher scores meaning worse organ dysfunction

Variation in cardiovascular sequential organ failure assessment score score 24 to 120 hours after randomization120 hours

Variation of the cardiovascular sequential organ failure assessment score score between baseline daily until 120 hours later. Cardiovascular sequential organ failure assessment score varies between 0 and +4 points, higher scores meaning worse cardiovascular dysfunction

Cumulative vasopressor dose for 120 hours after randomization120 hours

Dose of infused norephineprine and/or vasopressin during 120 hours after randomization

Length of stay in the ICU90 days

time spent in ICU

Cumulative vasopressor dose in the first 48 hours after randomization Translation results Cumulative vasopressor dose in the first 48 hours after randomization48 hours

Dose of infused norephineprine and/or vasopressin during the first 48 hours after randomization

Trial Locations

Locations (2)

Hospital São José

🇧🇷

Criciúma, Santa Catarina, Brazil

Hospital Maternidade São José de Colatina

🇧🇷

Colatina, Espirito Santo, Brazil

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