Septic ShockPhase 3NCT05207280
Clinical Trial Comparing Noradrenaline (NA) Plus Placebo Versus Noradrenaline Plus Terlipressin (TP) in Septic Shock
A Phase 3 study testing Noradrenaline plus Terlipressin in people with Septic Shock, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 10 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Noradrenaline plus Terlipressin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 10 sitesSpain
- Study dates
- 11 Oct 2022to Nov 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (18 years or older).
- Patients with septic shock
- 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.
Who cannot join
- Pregnant or lactating patients.
- Pathologies in which terlipressin is clinically indicated: gastrointestinal bleeding due to esophageal-gastric varices, hepatorenal syndrome.
- Patients diagnosed with unstable acute coronary syndrome.
- Patients with acute or chronic mesenteric ischemia.
- Patients with Raynaud's Phenomenon, or vasospastic disease.
- Patients participating in another intervention clinical trial.
Show all 10Show fewer
- Patients with active bleeding.
- Patients with renal replacement technique at the time of randomization.
- Patients with some limitation of life support treatment
- Previous use of terlipressin during your stay in the intensive Care Unit
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites, 10 recruiting
- Recruiting
Hospital San Juan de Dios del Aljarafe
Bormujos, Sevilla, 41930
José Luis García Garmendia, JoseLuis.GarciaGarmendia@sjd.es
- Recruiting
Hospital Puerta del mar
Cadiz, 11009
Rafael Sierra Camerino, rasierraca@gmail.com
- Recruiting
Hospital Universitario Reina Sofía
Córdoba, 14004
Carmen de la Fuente Martos, carmen.fuente.sspa@juntadeandalucia.es
Carmen de la Fuente Martos
- Recruiting
Hospital Universitario Virgen de las Nieves
Granada, 18014
María del Mar Jiménez Quintana, mmarjimenezquintana@hotmail.com
María del Mar Jiménez Quintana
- Recruiting
Hospital Universitario Clínico San Cecilio
Granada, 18016
Manuel Colmenero Ruiz, manuel.colmenero.sspa@juntadeandalucia.es
- Recruiting
Complejo Hospitalario de Jaén
Jaén, 23007
Ricardo Rivera Fernández, rriverafernandez@hotmail.com
Ricardo Rivera Fernández
- Recruiting
Hospital Universitario Jerez de la Frontera
Jerez de la Frontera, Cádiz, 11407
Rafael Estella García, litoestella@hotmail.com
- Recruiting
Hospital Universitario Regional de Málaga
Málaga, 29010
Manuel Herrera Gutiérrez, mehguci@gmail.com
Manuel Herrera Gutiérrez
- Recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
Clara Rosso Fernández, 955012144, claram.rosso.sspa@juntadeandalucia.es
Irene Borreguero Borreguero, 955007609, irene.borreguero@juntadeandalucia.es
- Recruiting
Hospital Universitario Virgen del Rocío
Seville, 41013
Rosario Amaya Villar, ramayavillar@gmail.com
Rosario Amaya Villar
About this study
Official title: Randomized Clinical Trial Comparing Noradrenaline Plus Placebo Versus Terlipressin Plus Noradrenaline for the Treatment of Septic Shock
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.
Read the 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.
- Conditions
- Septic Shock
- Being tested
- Noradrenaline plus Terlipressin
- Keywords
- Septic Shock
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Noradrenaline plus TerlipressinCombination product
Also called Noradrenaline plus placebo
Comparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock
| Study group | Role | What they receive |
|---|---|---|
| Noradrenaline plus Terlipressin | Experimental | Patients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours. Solution for infusion (Intravenous). And: Terlipressin with dose 1 mg every 6 hours diluted in a 50 mL serum to pass in 15-30 minutesin injectable solution. Intravenous (diluted in a 50 mL serum to pass in 15-30 minutes) Receives: Combination Product: Noradrenaline plus Terlipressin |
| Noradrenaline plus placebo | Placebo comparator | Patients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours in solution for infusion (Intravenous), and placebo with solution in vial with the same external appearance as terlipressin. 1 mg every 6 hours, diluted in a 50 mL serum to pass in 15-30 minutes in injectable solution Route of administration: Intravenous, diluted in a 50 mL serum to pass in 15-30 minutes Receives: Combination Product: Noradrenaline plus Terlipressin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Organ failure
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.
Measured: 72 hours
Days of life free of stay in the Intensive Care Unit
Number of the days of life free of stay in the Intensive Care Unit measured after the administration of terlipressin / placebo
Measured: 28 days
Secondary outcomes (11)
Lactate clearance
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.
Measured: 6, 12, 24 and 72 hours
Vasopressor-free days of life
Measure of vasopressor-free days of life
Measured: 28 days
Need of renal replacement therapies
Assessment of the change in the need of renal replacement therapies
Measured: 28 days
Mechanical ventilation-free days of life
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.
Measured: 28 days
vasopressor index
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.
Measured: 28 days
Mortality
Evaluation of the number of patients who die from the signing of the informed consent until day 28
Measured: 28 days
Mortality
Evaluation of the number of patients who die from the signing of the informed consent until day 90
Measured: 90 days
Adverse effects related to the administration of vasopressors
Measure of the adverse effects related to the administration of vasopressors until the end of study
Measured: 90 days
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
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
Measured: 90 days
Relation between the appearance of adverse effects and genetic variants of the receptor 1a and LNPEP.
Measure of the relation between adverse effects due to the use of terlipressin and genetic variants of the vasopressin receptor 1a and LNPEP
Measured: 90 days
Relation of the mortality with genetic variants of the receptor 1a and LNPEP.
Measure of the relation between the mortality with genetic variants of the vasopressin receptor 1a and LNPEP
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start11 Oct 2022
- Primary completionNov 2024 (estimated)
- Study completionNov 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, parallel, multicenter, double-blind clinical trial with two treatment arms
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- José Garnacho Montero, Principal investigator, Hospital Universitario Virgen Macarena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05207280
- Sponsor's protocol ID
- CONTENTSS
- Status last verified
- Apr 2023
- First submitted
- 18 Nov 2021
- Last updated
- 27 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial Comparing Noradrenaline Plus Placebo Versus Terlipressin Plus Noradrenaline for the Treatment of Septic Shock
- ClinicalTrials.gov ID
- NCT05207280
- Acronym / sponsor ID
- CONTENTSS
- Conditions
- Septic Shock
- Keywords
- Septic Shock
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 11 Oct 2022 (actual)
- Primary completion
- Nov 2024 (estimated)
- Study completion
- Nov 2024 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, parallel, multicenter, double-blind clinical trial with two treatment arms
| Arm | Type | Receives |
|---|---|---|
| Noradrenaline plus Terlipressin | Experimental | Combination Product: Noradrenaline plus TerlipressinPatients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours. Solution for infusion (Intravenous). And: Terlipressin with dose 1 mg every 6 hours diluted in a 50 mL serum to pass in 15-30 minutesin injectable solution. Intravenous (diluted in a 50 mL serum to pass in 15-30 minutes) |
| Noradrenaline plus placebo | Placebo comparator | Combination Product: Noradrenaline plus TerlipressinPatients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours in solution for infusion (Intravenous), and placebo with solution in vial with the same external appearance as terlipressin. 1 mg every 6 hours, diluted in a 50 mL serum to pass in 15-30 minutes in injectable solution Route of administration: Intravenous, diluted in a 50 mL serum to pass in 15-30 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients (18 years or older).
- Patients with septic shock
- 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.
Key exclusion criteria (10 listed)
- Pregnant or lactating patients.
- Pathologies in which terlipressin is clinically indicated: gastrointestinal bleeding due to esophageal-gastric varices, hepatorenal syndrome.
- Patients diagnosed with unstable acute coronary syndrome.
- Patients with acute or chronic mesenteric ischemia.
- Patients with Raynaud's Phenomenon, or vasospastic disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Noradrenaline plus TerlipressinAlso: Noradrenaline plus placeboComparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock | Combination product | Noradrenaline plus Terlipressin, Noradrenaline plus placebo |
Primary outcome
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
11 secondary outcomes
Lactate clearance
Time frame: 6, 12, 24 and 72 hours
Vasopressor-free days of life
Time frame: 28 days
Need of renal replacement therapies
Time frame: 28 days
Mechanical ventilation-free days of life
Time frame: 28 days
vasopressor index
Time frame: 28 days
Mortality
Time frame: 28 days
Mortality
Time frame: 90 days
Adverse effects related to the administration of vasopressors
Time frame: 90 days
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
Relation between the appearance of adverse effects and genetic variants of the receptor 1a and LNPEP.
Time frame: 90 days
Relation of the mortality with genetic variants of the receptor 1a and LNPEP.
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2023.
- Individual participant dataSharing planned: No
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ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
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Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
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Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Garnacho Montero principal investigator
Hospital Universitario Virgen Macarena
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Noradrenaline plus Terlipressin in people with Septic Shock, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 10 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Clara Rosso Fernández (955012144, claram.rosso.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Organ failure (time frame: 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023; AzTrials last refreshed its copy on 7 Nov 2026.