Clinical Trials Register

Summary
EudraCT Number:	2019-004328-39
Sponsor's Protocol Code Number:	INFUTER
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:	2020-02-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2019-004328-39

A.3

Full title of the trial

Hemodynamic profile of terlipressin and octreotide in patients with cirrhosis and portal hypertension. A randomised, single blinded clinical trial.

Perfil hemodinámico de la terlipresina y el octreotido en paciente con cirrosis e hipertensión portal. Ensayo clínico aleatorizado y enmascarado a ciego simple.

A.3.1

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

Clinical trial to compare the administration of a single dose of two different medicines in patients with hepatic cirrhosis and portal hypertension.

Ensayo clínico para comparar la administración de una única dosis de dos medicamentos distintos en pacientes con cirrosis hepática e hipertensión portal.

A.3.2

Name or abbreviated title of the trial where available

INFUTER

A.4.1

Sponsor's protocol code number

INFUTER

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	Fundació Clínic per a la Recerca Biomèdica_FCRB
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	FCRB
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	Fundació Clínic per a la Recerca Biomèdica_FCRB
B.5.2	Functional name of contact point	FCRB
B.5.3	Address:
B.5.3.1	Street Address	C. Rosselló, 149-153
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	349322754009838
B.5.6	E-mail	jcgarcia@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	Glypressin
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring SAU
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	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TERLIPRESSIN
D.3.9.1	CAS number	14636-12-5
D.3.9.4	EV Substance Code	SUB10927MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.86
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	Sandostatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica SA
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	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Octreotide
D.3.9.1	CAS number	79517-01-4
D.3.9.3	Other descriptive name	OCTREOTIDE ACETATE
D.3.9.4	EV Substance Code	SUB03490MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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

The proposed study aims to investigate the hemodynamic effects of terlipressin and the time profile of these effects in patients with cirrhosis and portal hypertension when given as continuous infusion and compare it with that achieved when given as a bolus. In addition it also aims to evaluate the hemodynamic effects of octreotide in patients with cirrhosis and portal hypertension

El estudio propuesto tiene como objetivo investigar los efectos hemodinámicos de la terlipresina y el perfil de tiempo de estos efectos en pacientes con cirrosis e hipertensión portal cuando se administra como infusión continua y compararlo con el logrado cuando se administra como un bolo. Además tiene también como objetivo evaluar los efectos hemodinámicos de octreotida en pacientes con cirrosis e hipertensión portal.

E.1.1.1

Medical condition in easily understood language

To investigate the hemodynamic effects of terlipressin and octreotide the time profile of these effects in patients with cirrhosis and portal hypertension

Tiene como objetivo investigar los efectos hemodinámicos de la terlipresina yel octreotido y el perfil de tiempo de estos efectos en pacientes con cirrosis e hipertensión portal

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

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 compare the reduction in HVPG caused by three different regimens at 30 minutes, 1 and 2 hours after its administration. Terlipressin at continuous infusion, terlipressin as a bolus, octreotide as a bolus followed by a continuous infusion.

Comparar la reducción de HVPG causada por tres regímenes diferentes a los 30 minutos, 1 y 2 horas después de su administración. Terlipresina en infusión continua, terlipresina como bolo, octreótido como bolo seguido de una infusión continua.

E.2.2

Secondary objectives of the trial

Safety:
To compare the safety of the three regimens with regard to cardiovascular and GI effects

Exploratory Objective:
To evaluate the hemodynamic and cardiopulmonary effects of octreotide and terlipressin in patients with cirrhosis and portal hypertension

La seguridad:
Comparar la seguridad de los tres regímenes con respecto a los efectos cardiovasculares y gastrointestinales.

Objetivo exploratorio:
Evaluar los efectos hemodinámicos y cardiopulmonares de octreotida y terlipresina en pacientes con cirrosis e hipertensión portal.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18-75 years old.
2. Liver cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. Cirrhosis of any aetiology may be included.
3. Child-Pugh B patients or Child-Pugh C patients (up to 12 points).
4. Portal hypertension (defined as HVPG ≥12mmHg, confirmed during hepatic vein catheterisation)
5. Stable disease in the absence of vasoactive agents
6. Signed informed consent form

1. Edad: 18-75 años.
2. Cirrosis hepática
3. Hipertensión portal
4. Enfermedad estable en ausencia de fármacos vasoactivos
5. Firma del consentimiento informado

E.4

Principal exclusion criteria

1. Patients on medications that can prolong the QT interval, a prior history of QT prolongation or on any medication with a known risk of QT prolongation and Torsade de Pointes.
2. Morbid obesity
3. Prior history of cardiovascular disease including ischemic heart disease or intestinal ischemia.
4. Plasma sodium <130mmol/l
5. Serum creatinine ≥2 mg/dL (176.8 µmol/L).
6. Serum bilirubin>5 mg/dL (85.5 µmol/L).
7. INR ≥2.5.
8. Bacterial infection within 10 days before study inclusion.
9. Gastrointestinal bleeding within 10 days before study inclusion.
10. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
11. Child-Pugh C patients (≥ 12 points).
12. Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months for uninodular HCC or for less than 12 months for multinodular HCC within Milan criteria. (Patients with HCC not fulfilling Milan criteria for liver transplant)
13. HIV infection.
14. Patients with a history of significant extra hepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD >2, chronic kidney disease with serum creatinine >2mg/dL or under renal replacement therapy.
15. Patients with current extra hepatic malignancies including solid tumours and hematologic disorders.
16. Pregnancy or breastfeeding.
17. Patients included in other clinical trials in the month before inclusion.
18. Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
19. Refusal to give informed consent.

1. Pacientes tratados con fármacos que prolongan el intervaloQT
2. Pacientes con carcinoma hepatocellular que no cumple los criterios de Milan para trasplante
3. Encefalopatía hepática grado II-IV
4. Sangrado digestivo en los últimos 10 días
5. Child-Pugh C de más de 12 puntos
6. Infección bacteriana en los últimos 10 días
7. HVPG <12mmHg
8. Sodio en plasma <130mmol/l
9. Creatinina sérica >2mg/dl
10. Biilirrubina >5mg/dl
11. INR>2.5
12. Enfermedad cardiovascular no controlada
13. Infección por HIV
14. Cáncer extrahepático
15. Insuficiencia cardiaca NYHA Grado III/IV, EPOC GOLD>2
16. Obesidad mórbida
17. Cardiopatía isquémica o isquemia intestinal
18. Embarazo o lactancia

E.5 End points

E.5.1

Primary end point(s)

Change in HVPG after 30 minutes, 1 hour and 2 hours of the administration of the three treatment regimens.

Cambio en HVPG después de 30 minutos, 1 hora y 2 horas de la administración de los tres regímenes de tratamiento.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 minutes, 1 hour and 2 hours

30 minutos, 1 hora y 2 horas

E.5.2

Secondary end point(s)

Safety measured by changes in blood pressure and ECG, and adverse effects of the three treatment guidelines
Changes in cardiopulmonary pressures and minute heart volume (blood pressure, heart rate, suprahepatic nailing and free pressure, nailed and free pulmonary blood pressure, right atrial pressure and cardiac output) after 30 minutes, 1 hour and 2 hours of administration of the three treatment guidelines

Seguridad medida mediante cambios en la presión arterial y ECG, y efectos adversos de las tres pautas de tratamiento
Cambios en las presiones cardiopulmonares y en el volumen minute cardiaco (presión arterial, frecuencia cardiaca, presión suprahepática enclavada y libre, presión arterial pulmonar enclavada y libre, presión auricular derecha y gasto cardiaco) tras 30 minutos, 1 hora y 2 horas de la administración de las tres pautas de tratamiento

E.5.2.1

Timepoint(s) of evaluation of this end point

30 minutes, 1 hour and 2 hours

30 minutos, 1 hora y 2 horas

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

LV/LP

Última visita del 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:

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

F.3.3.1

Women of childbearing potential not using contraception

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

Ninguno

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

2020-04-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-30

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials