Effects of Paroxetine on Cardiovascular Function in Septic Patients

NCT05725837 | Recruiting Phase 2

• 1 other identifier: Paroxetine
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

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.

Conditions

Septic Shock; Sepsis

Outcome Measures

Primary Outcomes (1)

• Time to vasopressor discontinuation

  Discontinuation of all vasopressors for at least 48 consecutive hours

  28 days of enrollment

Secondary Outcomes (6)

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

  48 hours

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

  120 hours

• Cumulative vasopressor dose for 120 hours after randomization

  120 hours

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

  120 hours

• Length of stay in the ICU

  90 days

Other Outcomes (3)

• Neutrophilic levels of total and phosphorylated GRK2

  120 hours

• Plasma levels of cytokines and chemokines

  120 hours

• Internalization of CXCR2 receptors in neutrophils

  120 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

40mg, single dose a day, by mouth or enteric tube

Drug: Paroxetine

Paroxetine

EXPERIMENTAL

40mg, single dose a day, by mouth or enteric tube

Drug: Paroxetine

Interventions

Paroxetine DRUG

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

Paroxetine; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude: lead

Study Sites (2)

Hospital Maternidade São José de Colatina

Colatina, Espírito Santo, Brazil

RECRUITING

Hospital São José

Criciúma, Santa Catarina, 88801460, Brazil

RECRUITING

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

felipe dal-pizzol, MD

CONTACT

+55 48 991852300; fdpizzol@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: After 20 patients randomized the advisory board will unblind subjects to determine if the fluoxetine arm should be continued. Since it is not expected to have any beneficial effect of this treatment (it is only a comparative control to the effect of paroxetine on serotonin metabolism). Based on the decision of the committee the study could exclude the serotonin arm and the definitive sample size is going to be calculated. The fluoxetine group was removed from the study after analysis of the first 20 patients (as foreseen in the initial protocol, after 20 patients included the blind would be broken to determine the final sample size) as it did not present an apparent benefit in the primary outcome. Considering that it had been included as a comparator for the effect of paroxetine on serotonin metabolism, and no beneficial effect from its use was anticipated, the study management committee decided to withdraw it.

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 13, 2023
• Study Start: June 10, 2023
• Primary Completion: March 15, 2025
• Study Completion: April 15, 2025
• Last Updated: January 6, 2025

Record last verified: 2025-01

Locations

BR (2)