Effects of Paroxetine on Cardiovascular Function in Septic Patients

Sepsis Clinical Trial

Official title:

Effects of Paroxetine on Cardiovascular Function in Septic Patients: a Randomized Placebo Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05725837
• Other study ID #: Paroxetine
• Status: Recruiting
• Phase: Phase 2
• Start date: June 10, 2023
• Est. completion date: July 15, 2024

Study information

• Verified date: May 2024
• Source: Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude
• Contact: felipe dal-pizzol, MD
• Phone: +55 48 991852300
• Email: fdpizzol[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: July 15, 2024
• Est. primary completion date: July 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Shock, Septic

Intervention

Drug:
• Paroxetine
Paroxetine, 40mg/day, once a day, for 05 consecutive days or 24 hours after shock resolution

Locations

Country	Name	City	State
Brazil	Hospital Maternidade São José de Colatina	Colatina	Espirito Santo
Brazil	Hospital São José	Criciúma	Santa Catarina

Sponsors (1)

Lead Sponsor	Collaborator
Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neutrophilic levels of total and phosphorylated GRK2	Expression of GRK-2 measured by western blot in isolated neutrophils	120 hours
Other	Plasma levels of cytokines and chemokines	Plasma levels of different cytokines and chemokines measured by ELISA	120 hours
Other	Internalization of CXCR2 receptors in neutrophils	Internalization of receptors known to be influenced by GRK-2 inhibitor by flow cytometry	120 hours
Primary	Time to vasopressor discontinuation	Discontinuation of all vasopressors for at least 48 consecutive hours	28 days of enrollment
Secondary	Cumulative vasopressor dose in the first 48 hours after randomization Translation results Cumulative vasopressor dose in the first 48 hours after randomization	Dose of infused norephineprine and/or vasopressin during the first 48 hours after randomization	48 hours
Secondary	Variation in cardiovascular sequential organ failure assessment score score 24 to 120 hours after randomization	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	120 hours
Secondary	Cumulative vasopressor dose for 120 hours after randomization	Dose of infused norephineprine and/or vasopressin during 120 hours after randomization	120 hours
Secondary	Total sequential organ failure assessment score score variation 24 to 120 hours after randomization	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	120 hours
Secondary	Length of stay in the ICU	time spent in ICU	90 days
Secondary	Mortality during ICU stay	Mortality in the ICU	90 daus