Clinical Trials Register

Summary
EudraCT Number:	2022-001858-33
Sponsor's Protocol Code Number:	SURVIC_STUDY
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-01-10
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2022-001858-33

A.3

Full title of the trial

Randomized controlled trial comparing conventional antibiotic strategies versus regimens guided by epidemiological surveillance in infected patients with cirrhosis.

Estidio controlado aleatorizado que compara estrategias antibióticas convencionales frente a regímenes guiados por la vigilancia epidemiológica en pacientes infectados con cirrosis.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Randomized controlled study comparing conventional antibiotic regimens versus antimicrobial strategies guided by epidemiological surveillance in patients infected with cirrhosis.

Estudio aleatorizado y controlado en el que se comparan esquemas antibióticos convencionales frente a estrategias antimicrobianas guiadas por vigilancia epidemiológica en pacientes infectados con cirrosis.

A.4.1

Sponsor's protocol code number

SURVIC_STUDY

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	IDIBAPS (Institit d'Investigacions Biomèdiques August Pi I Sunyer)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Instituto de Salud Carlos III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hospital Clinic - IDIBAPS
B.5.2	Functional name of contact point	Javier Fernández
B.5.3	Address:
B.5.3.1	Street Address	Villarroel, 170
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08036
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34932275400
B.5.6	E-mail	jfdez@clinic.cat

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Treatment according to the germs detected in nasal and rectal swabs.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Empirical treatment according to the guidelines "Prophylaxis and treatment of bacterial and fungal infections in cirrhosis" of the Hospital Clínic de Barcelona.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hospitalized patients with decompensated cirrhosis, diagnosed with bacterial infection evolution lasting for 48 hours or less.

Pacientes hospitalizados con cirrosis descompensada, diagnosticados de infección bacteriana de 48 horas o menos de evolución.

E.1.1.1

Medical condition in easily understood language

Patients with cirrhosis, aggravated by the development of a bacterial infection and requiring hospital admission.

Pacientes con cirrosis, agravada por el desarrollo de una infección bacteriana y que ha requirido ingreso en el hospital.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10021804
E.1.2	Term	Infection bacterial
E.1.2	System Organ Class	100000004862

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10064704
E.1.2	Term	Decompensated cirrhosis
E.1.2	System Organ Class	100000004871

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the probability/rate of antibiotic resistance development at 28 days after inclusion in both groups of patients, defined based on the appearance of new colonizations and/or infections by MDROs.

Evaluar la probabilidad/tasa de desarrollo de resistencia a antibióticos a los 28 días tras la inclusión en ambos grupos de pacientes, definida en base a la aparición de nuevas colonizaciones y/o infecciones por MDROs.

E.2.2

Secondary objectives of the trial

1. Evaluate:
- Probability and rate of antibiotic resistance development during hospitalization.
- Probability and rate of MDROs colonization during hospitalization and at 28 days.
- Probability and rate of MDROs infection during hospitalization and at 28 days.
- Infection resolution rate.
- Evolution of severity scores: ACLF, MELD, Child-Pugh, CLIF-OF, CLIF-C AD, and CLIF-C ACLF score (inclusion, infection resolution or day 7, reinfection, hospital discharge and hospital readmission).
2. To determinate the days of admission to the ICU if needed.
3. To determinate the days of life support if needed.
4. To determinate the days of hospital stay.
5. To determinate the number of rehospitalizations.
6. To determinate the antibiotics consumption and health costs.
7. To evaluate the safety of both antibiotic strategies (AE and SAE related and SUSARS and other SAEs).
8. Hospital and 28 days survival (rate and probability).

1. Evaluar:
- Probabilidad y tasa de desarrollo de resistencia a antibióticos durante hospitalización
- Probabilidad y tasa de colonización de MDROs durante la hospitalización y a los 28 días
- Probabilidad y tasa de infección por MDROs durante la hospitalización y a los 28 días
- Tasa de resolución de la infección
- Evolución de las puntuaciones de gravedad: ACLF, MELD, Child-Pugh, CLIF-OF, CLIF-C AD y puntuación CLIF-C ACLF (inclusión, resolución de la infección o día 7, reinfección, alta hospitalaria y reingreso hospitalario)
2. Determinar los días de ingreso en la UCI si es necesario
3. Determinar los días de soporte vital si es necesario
4. Determinar los días de estancia hospitalaria
5. Determinar el número de rehospitalizaciones
6. Determinar el consumo de antibióticos y los costes sanitarios
7. Evaluar la seguridad de ambas estrategias antibióticas (AA, AAGs relacionados y RAGIs y otros AAGs)
8. Supervivencia hospitalaria y a los 28 días (tasa y probabilidad).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients included into the study must meet all the following criteria:

1. Cirrhotic patients with acute decompensation aged ≥18 years.
2. Proven or suspected bacterial infection requiring antibiotic therapy (diagnosis will be established according to local guidelines, Appendix 1).
3. Signed informed consent or consent given by their legal representatives or close relatives.

Los pacientes incluidos en el estudio deberán cumplir los siguientes criterios:

1. Pacientes cirróticos con descompensación aguda de edad ≥18 años.
2. Confirmación o sospecha de infección bacteriana que requiera tratamiento antibiótico (el diagnóstico se establecerá según las directrices locales, Apéndice 1).
3. Paciente, represente legal o familiares cercanos firmen el consentimiento informado.

E.4

Principal exclusion criteria

Potential participants who meet any of the following criteria will be excluded from participation in this study:
1. Bacterial infection lasting for > 48 hours.
2. Infection in a critically ill cirrhotic patient (ICU admission). In this population, epidemiological surveillance is standard clinical prac-tice.
3. Evidence of current locally advanced or metastatic malignancy (pa-tients with hepatocellular carcinoma within the Milan criteria and non-melanocytic skin cancer can be included).
4. Pregnant and/or breast-feeding woman.
5. Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surro-gate decision-maker and it appears unlikely that the patient will re-gain consciousness or sufficient ability to provide delayed informed consent.

Los potenciales participantes que cumplan algunos de los siguientes criterios serán excluidos del estudio:
1. Infección bacteriana de duración > 48 horas.
2. Infección en un paciente cirrótico en estado crítico (ingreso en la UCI). En esta población, la vigilancia epidemiológica es una práctica clínica habitual.
3. Evidencia de malignidad actual localmente avanzada o metastásica (pueden incluirse Pacientes con carcinoma hepatocellular dentro de los criterios de Milan y cáncer de piel no melanocítico).
4. Mujer embarazada y/o en período de lactancia
5. Pacientes que no puedan dar el consentimiento informado previo y cuando haya pruebas documentadas de que el paciente no tiene un sustituto legal para tomar decisiones y parezca poco probable que el paciente recupere la conciencia o la capacidad suficiente para dar un consentimiento informado tardío.

E.5 End points

E.5.1

Primary end point(s)

Probability/rate of participants of developing antibiotic resistance in both treatment arms at 28 days (composite variable: MDRO colonization and/or infection).

Probabilidad/tasa de los participantes de desarrollar resistencia a los antibióticos en ambos brazos de tratamiento a los 28 días (variable compuesta: colonización y/o infección por MDRO).

E.5.1.1

Timepoint(s) of evaluation of this end point

28 day

día 28

E.5.2

Secondary end point(s)

1. Evaluate the impact of both antibiotic strategies on:
- Rate and probability of developing antibiotic resistance during hospitalization.
- Rate and probability of MDRO colonization during hospi-talization and at 28 days.
- Rate and probability of MDRO infection during hospitaliza-tion and at 28 days.
- Infection resolution rate with initial and final strategies.
- Evolution of scores: ACLF, MELD, Child-Pugh, CLIF-OF, CLIF-C AD, and CLIF-C ACLF score (inclusion, infection resolution or day 7, reinfection, hospital discharge and hospital readmission).
2. Days of admission to the ICU if needed.
3. Days of life support (dialysis, vasopressors, and mechanical ventila-tion) if needed.
4. Days of hospital stay.
5. Number of rehospitalizations.
6. Antibiotics consumption (days, dose and type of antibiotics) and health costs (cost of antibiotic, cost of hospital/ICU stay and of organ support(s)).
7. Proportion of participants with antibiotic-related AE, SAEs, SUSARs and other SAEs.
8. Hospital and 28-day survival.

1. Evaluar el impacto de ambas estrategias antibióticas en:
- Tasa y probabilidad de desarrollar resistencia a los antibió-ticos durante la hospitalización.
- Tasa y probabilidad de colonización por MDRO durante la hospitalización y a los 28 días.
- Tasa y probabilidad de infección por MDRO durante la hospitalización y a los 28 días.
- Tasa de resolución de infecciones con estrategias iniciales y finales.
- Evolución de las puntuaciones: ACLF, MELD, Child-Pugh, CLIF-OF, CLIF-C AD y CLIF-C ACLF score (inclusión, resolu-ción de la infección o día 7, reinfección, alta hospitalaria y reingreso hospitalario).
2. Días de ingreso en la UCI si es necesario.
3. Días de soporte vital (diálisis, vasopresores y ventilación mecánica) si es necesario.
4. Días de estancia en el hospital.
5. Número de rehospitalizaciones.
6. Consumo de antibióticos (días, dosis y tipo de antibióticos) y costes sanitarios (coste del antibiótico, coste de la estancia en el hospi-tal/UCI y de los órganos de soporte).
7. Proporción de participantes con AA y AAGs relacionados con los antibióticos y RAGIs y otros AAGs.
8. Supervivencia hospitalaria y a los 28 días.

E.5.2.1

Timepoint(s) of evaluation of this end point

Inclusion, infection resolution or day 7, reinfection, during hospitalization, hospital discharge, hospital readmission and at 28 days.

Inclusión, resolución de la infección o día 7, reinfección, durante la hospitalizaciób, alta hospitalaria, reingreso hospitalario y a los 28 días.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLP

LVLS (última visita último paciente)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

188

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

In case the subjects are unable to give informed consent, a legal representative can give consent.

En caso que los sujetos no puedan dar el consentimiento informado, un reperentante legal puede dar el consentimiento.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

198

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-01

P. End of Trial
P.	End of Trial Status	Ongoing

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