Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
152
Countries
1
Sites
10
Septic Shock
Main objective is composed by: -Reduction of organ failure evaluated by Sepsis realted Organ failure Assessment score (SOFA scale) 72 h after administration of terlipressin / placebo. -Increase in ICU-free days of life measured 28 days after administration of terlipressin / placebo
Key facts
- Sponsor
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 26 Jun 2024 → 28 Dec 2024
- Decision date (initial)
- 2024-06-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Insituto de Salud Carlos III
External identifiers
- EU CT number
- 2024-514149-12-00
- EudraCT number
- 2020-005756-37
- ClinicalTrials.gov
- NCT05207280
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacoeconomic, Therapy, Efficacy
Main objective is composed by:
-Reduction of organ failure evaluated by Sepsis realted Organ failure
Assessment score (SOFA scale) 72 h after administration of terlipressin
/ placebo.
-Increase in ICU-free days of life measured 28 days after administration
of terlipressin / placebo
Secondary objectives 10
- Increase in lactate clearance at 6, 12, 24 and 72 h after administration of terlipressin / placebo
- Increase in the days with life free of mechanical ventilation measured at 28 days
- Increase in vasopressor-free days of life measured at 28 days
- Mortality at 28 days and 90 days
- Reduction of the need for continuous renal replacement therapy
- Reduction of the total equivalent dose of vasopressors
- No increase in adverse effects related to the administration of vasopressors.
- Association with mortality of genetic variants of the vasopressin receptor 1a and LNPEP
- Association between achievement of the combined primary objective and genetic variants of the vasopressin receptor 1a and LNPEP.
- Association between the appearance of adverse effects due to the use of terlipressin and genetic variants of the vasopressin receptor 1a and LNPEP.
Conditions and MedDRA coding
Septic Shock
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.1 | PT | 10040070 | Septic shock | 100000004862 |
| 20.0 | LLT | 10040089 | Septicemia | 10021881 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Noradrenaline plus placebo vs noradrenaline plus terlipressin for the treatment of septic shock Double blind randomized clinical trial comparing noradrenaline plus placebo versus noradrenaline plus terlipressin in septic shock
|
Randomised Controlled | Double | [{"id":67373,"code":1,"name":"Subject"},{"id":67372,"code":3,"name":"Monitor"},{"id":67371,"code":2,"name":"Investigator"}] | Experimental treatment: Patients who require noradrenaline at a dose equal to or greater than 0.2 μg/kg/min for at least 3 hours and no more than 12 hours from the moment the patient becomes recruitable, considered for inclusion in the study, are administered terlipressin at a dose of 1 mg every 6 hours diluted in 50 mL of saline to be administered over 15-30 minutes, at a dose of 1 mg every 6 hours. Control treatment: Patients who require a baseline noradrenaline infusion at a dose equal to or greater than 0.2 μg/kg/min for at least 3 hours and no more than 12 hours from the moment the patient becomes recruitable, considered for inclusion in the study, are subsequently administered a placebo, indistinguishable from the terlipressin vial, every 6 hours. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Adult patients (18 years or older).
- Patients with septic shock.
- Patients with a SOFA index> 4 points. (If the patient is going to be intubated at the time of randomization, take the neurological SOFA score from the medical record)
- Signature of the informed consent by the patient or his or her legal representative. (Informed consent may be granted by phone if the legal representative is not present at the center at the time of signing, with written re-consent required as soon as possible)
Exclusion criteria 12
- Pregnant or lactating patients
- Pathologies on 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.
- Patients with active bleeding.
- Patients with renal replacement technique at the time of randomization.
- Patients with some limitation of life support treatment (LLST).
- Previous use of terlipressin during your stay in the ICU
- Previous use of vasopressin.
- Known allergy to terlipressin
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Reduction of organ failure evaluated by SOFA scale
- Increase in ICU-free days of life
Secondary endpoints 10
- Increase in lactate clearance.
- Increase of the days with life free of mechanical ventilation.
- Increase in vasopressor-free days of life
- Mortality
- Reduction of the need for continuous renal replacement therapy (CRRT).
- Reduction of the total equivalent dose of vasopressors
- No increase in adverse effects related to the administration of vasopressors
- Association of mortality with genetic variants of the vasopressin 1a receptor and the LNPEP gene.
- Association between the achievement of the combined primary endpoint and the genetic variants of the vasopressin receptor 1a and the LNPEP gene.
- Association between the appearance of adverse effects due to the use of terlipressin, and the genetic variants of the Vasopressin 1a receptor and LNPEP gene.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Terlipresina acetato EVER Pharma 1 mg solución inyectable
PRD5781489 · Product
- Active substance
- Terlipressin Acetate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 4 mg/kg milligram(s)/kilogram
- Max total dose
- 4 mg/kg milligram(s)/kilogram
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- H01BA04 — TERLIPRESSIN
- Marketing authorisation
- 82806
- MA holder
- EVER VALINJECT GMBH
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
SCP14402750 · ATC
- Active substance
- Noradrenaline Tartrate
- Substance synonyms
- NOREPINEPHRINE BITARTRATE, LEVARTERENOL ACID TARTRATE, ARTERENOL ACID TARTRATE, NOREPINEPHRINE HYDROGEN TARTRATE
- Route of administration
- SOLUTION FOR INFUSION
- Max daily dose
- 0.2 µg/Kg microgram(s)/kilogram
- Max total dose
- 5.6 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CA03 — NOREPINEPHRINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Solution in a vial with the same external appearance as terlipressin
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Sponsor organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Address
- Avenida De Manuel Siurot Sn
- City
- Sevilla
- Postcode
- 41013
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Contact name
- UICEC HUVR-HUVM
Public contact point
- Organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Contact name
- UICEC HUVR-HUVM
Locations
1 EU/EEA country · 10 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ended | 152 | 10 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario Regional De Malaga
UGC Cuidados Intensivos, Avenida De Carlos De Haya Sn, 29010, Malaga
Hospital Universitario Virgen De Las Nieves
UGC Cuidados Intensivos, Avenida De Las Fuerzas Armadas 2, 18014, Granada
Hospital Universitario Puerta Del Mar
UGC Cuidados Intensivos, Avenida De Ana De Viya 21, 11009, Cadiz
Hospital Universitario Clínico San Cecilio
UGC Cuidados Intensivos, Avda. del Conocimiento, s/n, Granada
Hospital De Jerez De La Frontera
UGC Cuidados Intensivos, Carretera De La Ronda Circunvalacion S/n, 11407, Jerez De La Frontera
Hospital Universitario De Jaen
UGC Cuidados Intensivos, Avenida Del Ejercito Espanol 10, 23007, Jaen
Hospital Universitario Reina Sofia
UGC Cuidados Intensivos, Avda. Menéndez Pidal s/n, 14004, Córdoba
Hospital Universitario Virgen del Rocío
UGC Cuidados Intensivos, Avda. Manuel Siurot, S/n, Sevilla
Hospital San Juan de Dios del Aljarafe
UGC Cuidados Intensivos, Ada. San Juan de Dios S/N, 41930, Bormujos
Hospital Universitario Virgen De La Macarena
UGC Cuidados Intensivos, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2024-06-26 | 2024-06-26 | 2024-09-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| INFORME RESUMEN RESULTADOS ENSAYO CONTENTSS SUM-129439
|
2026-04-16T12:47:38 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| INFORME RESUMEN RESULTADOS ENSAYO CONTENTSS PARA PÚBLICO NO EXPERTO | 2026-04-16T12:48:32 | Submitted | Laypersons Summary of Results |
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | CONTENTSS_Informe Resumen Resultados PERSONAL LEGO | 1 |
| Protocol (for publication) | D1_Protocol 2024-514149-12-00 | 5.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Terlipresina | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | ES_SmPC_Noradrenalina | 1 |
| Summary of results (for publication) | CONTENTSS_Informe Resumen Resultados | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-514149-12-00 | 4 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-20 | Spain | Acceptable 2024-06-04
|
2024-06-04 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-01 | Spain | Acceptable 2024-08-29
|
2024-08-29 |