COMBINATION_PRODUCT
Noradrenaline plus Terlipressin
Comparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock
Clinical Trial Comparing Noradrenaline (NA) Plus Placebo Versus Noradrenaline Plus Terlipressin (TP) in Septic Shock
Status
Unknown
Phase
Phase 3
Enrollment
152
Locations
10
Results
Not posted
Publications
0
Study summary
What the protocol is testing.
Septic shock is a major health problem. In the clinical practice guidelines of the Surviving Sepsis Campaign is recommended to add vasopressin (VP) or epinephrine in case of not reaching the goal of mean arterial pressure (MAP) although with a low level of evidence. This is a clinical trial with the purpose of comparing the efficacy and safety of norepinephrine (NE) plus placebo versus NE plus terlipressin (TP) in adult patients with septic shock and with a Sepsis related Organ Failure Assessment score (SOFA)\> 4 points. The primary objective will be a combined end-point: reduction of organic dysfunction measured at 72 h by SOFA score and by the increase in ICU (Intensive care unit) -free days measured at 28 days.
Full detailed description
Introduction: Septic shock is a major health problem. The clinical practice guidelines of the Surviving Sepsis Campaign establish the use of NE if after resuscitation with fluids a MAP\> 65 mm Hg is not achieved. In these guidelines, it is recommended to add VP or epinephrine in case of not reaching the goal of MAP although with a low level of evidence. TP is a synthetic analogue of VP with a long half-life. Preliminary studies on the use of TP associated with NE have not shown a decrease in mortality, although a reduction in organic dysfunction at 72 h, with discordant data regarding the rate of adverse events. Material and Methods: Randomized, parallel, double-blind and multicenter clinical trial with the purpose of comparing the efficacy and safety of NE plus placebo versus NE plus TP in adult patients with septic shock and with a SOFA score\> 4 points. The threshold dose of NE\> 0.2 µg / kg / min is chosen to associate the second vasopressor (TP or placebo). The primary objective will be a combined end-point: reduction of organic dysfunction measured at 72 h by SOFA score and by the increase in ICU -free days measured at 28 days. The secondary objectives will be: mortality at 28 and 90 days, the need of renal replacement therapies, mechanical ventilation-free days, vasopressor-free days, and adverse reactions. Sample size of 152 patients (76 per arm), stratified by center and severity of illness. In addition, 6 single nucleotide polymorphisms of the vasopressin V1a receptor and a polymorphism of leucyl / cystinyl aminopeptidase or vasopressinase will be determined to establish its association with mortality in septic shock and with the efficacy and the occurrence of adverse effects due to the use of TP.
Interventions
Treatment arms and agents.
Timeline
From registration to results.
First posted
Jan 26, 2022
Study start
Oct 11, 2022
Primary completion
Nov 2024
Study completion
Nov 2024
Results posted
Not reported
Registry updated
Apr 27, 2023
Outcomes
What the study measures.
Primary outcomes
Organ failure
Time frame · 72 hours
Number of organ failures related sepsis. Assessment Sepsis related Organ Failure Assessmen scale (SOFA scale) after administration of terlipressin / placebo. These scale assesses organ dysfunction. In patients with infection, a SOFA score ≥ 2 points (in patients with chronic organ dysfunction, a 2 point increase from baseline score) is diagnostic of sepsis.
Days of life free of stay in the Intensive Care Unit
Time frame · 28 days
Number of the days of life free of stay in the Intensive Care Unit measured after the administration of terlipressin / placebo
Secondary outcomes
Lactate clearance
Time frame · 6, 12, 24 and 72 hours
Measure of the difference between lactate in arterial blood measured at the beginning of vasopressor treatment and that measured at 6, 12, 24 and 72 hours.
Vasopressor-free days of life
Time frame · 28 days
Measure of vasopressor-free days of life
Need of renal replacement therapies
Time frame · 28 days
Assessment of the change in the need of renal replacement therapies
Mechanical ventilation-free days of life
Time frame · 28 days
Measure of days free of mechanical ventilation, by means of the difference between 28 and the sum of the days the patient is under invasive mechanical ventilation or has died.
vasopressor index
Time frame · 28 days
Calculation of the vasopressor index, defined as dose of dopamine + dose of dobutamine + dose of epinephrine (x100) + dose of phenylephrine (x100) + dose of terlipressin / placebo.
Mortality
Time frame · 28 days
Evaluation of the number of patients who die from the signing of the informed consent until day 28
Mortality
Time frame · 90 days
Evaluation of the number of patients who die from the signing of the informed consent until day 90
Adverse effects related to the administration of vasopressors
Time frame · 90 days
Measure of the adverse effects related to the administration of vasopressors until the end of study
Relation between organ failure and days of life free of stay in the Intensive Care Unit with the genetic variants of the receptor 1a and LNPEP
Time frame · 90 days
Measure of the relation between number of organ failures related sepsis and number of the days of life free of stay in the Intensive Care Unit with the genetic variants of the vasopressin receptor 1a and LNPEP
Relation between the appearance of adverse effects and genetic variants of the receptor 1a and LNPEP.
Time frame · 90 days
Measure of the relation between adverse effects due to the use of terlipressin and genetic variants of the vasopressin receptor 1a and LNPEP
Eligibility
Who can take part.
- Minimum age
- 18 Years
- Maximum age
- Not reported
- Sex
- ALL
- Healthy volunteers
- No
Inclusion Criteria: 1. Adult patients (18 years or older). 2. Patients with septic shock 3. Patients with a SOFA \> 4 points. 5\. Oxygen saturation in the central venous system \> 70% 5. Central venous pressure\> 8 mmHg. 6. Signature of the informed consent by the patient or her legal representative. Exclusion Criteria: 1. Pregnant or lactating patients. 2. Pathologies in which terlipressin is clinically indicated: gastrointestinal bleeding due to esophageal-gastric varices, hepatorenal syndrome. 3. Patients diagnosed with unstable acute coronary syndrome. 4. Patients with acute or chronic mesenteric ischemia. 5. Patients with Raynaud's Phenomenon, or vasospastic disease. 6. Patients participating in another intervention clinical trial. 7. Patients with active bleeding. 8. Patients with renal replacement technique at the time of randomization. 9. Patients with some limitation of life support treatment 10. Previous use of terlipressin during your stay in the intensive Care Unit
Study locations
10 registered sites.
Spain. Showing up to 24 locations stored in the fast local snapshot.
Hospital Universitario Jerez de la Frontera
Jerez de la Frontera, Cádiz, Spain
Hospital San Juan de Dios del Aljarafe
Bormujos, Sevilla, Spain
Hospital Puerta del mar
Cadiz, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
Hospital Universitario Virgen de las Nieves
Granada, Spain
Hospital Universitario Clínico San Cecilio
Granada, Spain
Complejo Hospitalario de Jaén
Jaén, Spain
Hospital Universitario Regional de Málaga
Málaga, Spain
Hospital Universitario Virgen Macarena
Seville, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
Publications
Results and literature.
No PMID-linked publications were present in this registry snapshot.
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