Effects of Paroxetine on Cardiovascular Function in Septic Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: Paroxetine
Paroxetine, 40mg/day, once a day, for 05 consecutive days or 24 hours after shock resolution
Other Names:
|
| Sham Comparator: Fluoxetine Fluoxetine, as paroxetine, has activity upon serotonin uptake, but not on GRK-2 |
Drug: Paroxetine
Paroxetine, 40mg/day, once a day, for 05 consecutive days or 24 hours after shock resolution
Other Names:
|
| Experimental: Paroxetine
|
Drug: Paroxetine
Paroxetine, 40mg/day, once a day, for 05 consecutive days or 24 hours after shock resolution
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Variation of the cardiovascular sequential organ failure assessment score [48 hours]
Variation of the cardiovascular sequential organ failure assessment score score between baseline (shortly after enrollment in the study, before administration of the investigational product) and the value 48 hours later (time at which greater effect size is expected in view of the kinetics of paroxetine on expression / GRK2 phosphorylation). Cardiovascular sequential organ failure assessment score varies between 0 and +4 points, higher scores meaning worse cardiovascular dysfunction
Secondary Outcome Measures
- Cumulative vasopressor dose in the first 48 hours after randomization Translation results Cumulative vasopressor dose in the first 48 hours after randomization [48 hours]
Dose of infused norephineprine and/or vasopressin during the first 48 hours after randomization
- Variation in cardiovascular sequential organ failure assessment score score 24 to 120 hours after randomization [120 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 randomization [120 hours]
Dose of infused norephineprine and/or vasopressin during 120 hours after randomization
- Total sequential organ failure assessment score score variation 24 to 120 hours after randomization [120 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
- Length of stay in the ICU [90 days]
time spent in ICU
- Mortality during ICU stay [90 daus]
Mortality in the ICU
Other Outcome Measures
- Neutrophilic levels of total and phosphorylated GRK2 [120 hours]
Expression of GRK-2 measured by western blot in isolated neutrophils
- Plasma levels of cytokines and chemokines [120 hours]
Plasma levels of different cytokines and chemokines measured by ELISA
- Internalization of adrenergic and CXCR2 receptors in neutrophils [120 hours]
Internalization of receptors known to be influenced by GRK-2 inhibitor by flow cytometry
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient over 18 years of age;
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Patient diagnosed with septic shock for less than 48 hours and using a minimum dose of noradrenaline (0.01 mcg/kg/min);
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Patients and/or legal guardians who consented to participate in the study through the free and informed consent term before randomization.
Exclusion Criteria:
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Pregnant women;
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Patients with inability to use the gastrointestinal tract;
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Patients with known intolerance to paroxetine and/or fluoxetine;
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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);
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Patients in end-of-life care or with an expected survival of less than 24 hours at the time of eligibility
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Maternidade São José de Colatina | Colatina | Espirito Santo | Brazil | |
| 2 | Hospital São José | Criciúma | Santa Catarina | Brazil | 88801460 |
Sponsors and Collaborators
- Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Paroxetine