Clinical Trials Register

Summary
EudraCT Number:	2014-003597-17
Sponsor's Protocol Code Number:	FAR-NP-2014-01
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:	2014-10-16
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

2014-003597-17

A.3

Full title of the trial

Pilot, randomized, double-blind clinical trial to determine the phytosterolaemia in hospitalized patients treated with total parenteral nutrition and gamma-glutamyltransferase alteration

ENSAYO CLÍNICO PILOTO, RANDOMIZADO, DOBLE CIEGO, PARA DETERMINAR LA FITOSTEROLEMIA PLASMÁTICA EN PACIENTES ADULTOS HOSPITALIZADOS, TRATADOS CON NUTRICIÓN PARENTERAL TOTAL Y CON ALTERACIÓN DE LA GAMMAGLUTAMILTRANSFERASA

A.3.1

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

Pilot, randomized, double-blind clinical trial to determine the phytosterols in blood in hospitalized patients treated with total parenteral nutrition and gamma-glutamyltransferase alteration

ENSAYO CLÍNICO PILOTO, RANDOMIZADO, DOBLE CIEGO, PARA DETERMINAR LOS FITOSTEROLES EN SANGRE EN PACIENTES ADULTOS HOSPITALIZADOS, TRATADOS CON NUTRICIÓN PARENTERAL TOTAL Y CON ALTERACIÓN DE LA GAMMAGLUTAMILTRANSFERASA

A.3.2

Name or abbreviated title of the trial where available

Phystosterolemia and liver function in hospitalized adults treated with parenteral nutrition

Fistosterolemia y función hepática en adultos hospitalizados con nutrición parenteral

A.4.1

Sponsor's protocol code number

FAR-NP-2014-01

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	Josep Llop Talaveron
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	Sociedad Española de Farmacia Hospitalaria (SEFH) 2013/2014
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 Universitari de Bellvitge
B.5.2	Functional name of contact point	Josep M Llop Talaveron
B.5.3	Address:
B.5.3.1	Street Address	Feixa Llarga sn
B.5.3.2	Town/ city	L'Hospitalet de Llobregat
B.5.3.3	Post code	08907
B.5.3.4	Country	Spain
B.5.6	E-mail	josep.llop@bellvitgehospital.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	Omegaven
D.2.1.1.2	Name of the Marketing Authorisation holder	Fresenius Kabi
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Emulsion for 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	EICOSAPENTANOIC ACID/DOCOSAHEXAENOIC ACID
D.3.9.3	Other descriptive name	Fish oil
D.3.9.4	EV Substance Code	SUB28845
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Clinoleic
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter
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	Emulsion for 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	REFINED OLIVE OIL AND REFINED SOYA OIL
D.3.9.2	Current sponsor code	8524839
D.3.9.4	EV Substance Code	SUB32333
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

Adult hospitalized patients with parenteral nutrition and liver disfunction

Pacientes adultos hospitalizados con función hepática alterada y en tratamiento con nutrición parenteral

E.1.1.1

Medical condition in easily understood language

Adult hospitalized patients with parenteral nutrition and liver alteration

Pacientes adultos hospitalizados con alteración en el hígado y en tratamiento con nutrición parenteral

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10008641
E.1.2	Term	Cholestatic liver disease
E.1.2	System Organ Class	100000004871

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10074151
E.1.2	Term	Parenteral nutrition associated liver disease
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

In hospitalized adult patients with alteration of the liver function parameters after seven days of administration of the parenteral nutrition, lipid supply will be reduced by 50%. After this reduction, the main objectives are:
- To determine whether to switch to lipid emulsions of fish oil are more effective in reducing plasma levels of phytosterols than to maintain an emulsion of vegetable origin.
- To determine the correlation between phytosterolaemia in both groups with the changing values ??of gamma glutamyl transferase.

En pacientes adultos hospitalizados que presenten alteración de los parámetros de la función hepática después de siete días de administración de nutrición parenteral se reducirá el aporte lipídico un 50%. Tras esta reducción, los objetivos principales son:
- Determinar si cambiar a emulsiones lipídicas de aceite de pescado es más efectiva en la reducción de valores plasmáticos de fitoesteroles plasmáticos que mantener una emulsión de origen vegetal.
- Determinar la correlación entre los niveles plasmáticos de fitoesteroles en ambos grupos con la evolución de los valores de gamma glutamil transferasa.

E.2.2

Secondary objectives of the trial

Secondary objectives are:
- To determine the correlation between plasma levels of phytosterols and the evolution of the values ??of GGT.
- To determine the correlation between plasma levels of phytosterols in both groups with alkaline phosphatase, alanine aminotransferase and total bilirubin values.
- To determine the correlation between plasma levels of phytosterols in both groups with inflammatory response, expressed as C-reactive protein, interleukin 6, tumor necrosis factor and interleukin-10
- To evaluate the safety of switching to emulsions with omega 3 fatty acids by monitoring plasma determinations: triglycerides, platelet count and prothrombin time.
- To determine the correlation between plasma levels of phytosterols in patients and the amount of phytosterols administered.

Los objetivos secundarios son:
- Determinar la correlación entre los niveles plasmáticos de fitoesteroles y la evolución de los valores de la GGT.
- Determinar la correlación entre los niveles plasmáticos de fitoesteroles en ambos grupos con la evolución de los valores de la fosfatasa alcalina, alanina aminotransferasa y bilirrubina total.
- Determinar la correlación entre los niveles plasmáticos de fitoesteroles en ambos grupos con la respuesta inflamatoria: proteina C reactiva, interleucina 6, factor de necrosis tumoral e interleucina 10
- Evaluar la seguridad del cambio a emulsiones con ácidos grasos omega 3 mediante el seguimiento de las determinaciones plasmáticas: triglicéridos, recuento de plaquetas y el tiempo de protrombina.
- Determinar la correlación entre los niveles plasmáticos de fitoesteroles de los pacientes y la cantidad de fitoesteroles administrados.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients admitted to the Department of General and Digestive Surgery who meet ALL the criteria:
1. Adult hospitalized patients with parenteral nutrition and normal initial values ??of the liver function parameters (GGT, ALT, AST, ALP and total bilirubin), who after at least 7 days of treatment with NP present GGT values ??greater than or equal to twice the normal value (2 x the upper limit of normal).
2. Must be 18 years or more and may be of either sex and of any race / ethnicity.
3 shall be ready to give their written informed consent to the test and be able to do consent. If a subject can not give written informed consent independently, you can do your legal representative in place.3. Subjects must be willing to give their written informed consent for the test and be able to do. If a subject can not grant your informe consent written independently, you can do your legal representative in place in those cases included in the RD223/2004.

Pacientes ingresados en el Servicio de Cirugía General y Digestiva del centro hospitalario participante que cumplan TODOS los criterios:
1. Pacientes adultos hospitalizados con NP y valores iniciales normales de los parámetros de la función hepática (GGT, ALT, AST, FA y bilirrubina total) que después de un mínimo de 7 días de tratamiento con NP presenten valores de GGT superiores o iguales al doble del valor normal (2 x el límite superior de normalidad).
2. Deberán tener 18 años o más y podrán ser de ambos sexos y de cualquier raza/etnia.
3. Deberán estar dispuestos a otorgar su consentimiento informado por escrito para el ensayo y ser capaces de hacerlo. Si un sujeto no puede otorgar su consentimiento informado por escrito de forma independiente, podrá hacerlo su representante legal en su lugar.

E.4

Principal exclusion criteria

1. Background of type I hypersensitivity or idiosyncratic reaction to any component of the intravenous lipid emulsions.
2. Pregnant or lactating
3. Plasma triglycerides> 3 mmol/L
4. Treatment with corticosteroids or immunosuppressive chronically in the previous month.
5. AIDS patients
6. Transplanted
7 Contraindications according to the data sheet of the lipid emulsions

1. Antecedentes de hipersensibilidad de tipo I ni de reacciones idiosincrásicas a ningún componente de las emulsiones lipídicas intravenosas.
2. Mujeres embarazadas o en período de lactancia
3. Triglicéridos plasmáticos >3 mmol/L
4. Tratamiento con corticoides de forma crónica o inmunosupresores en el mes previo.
5. Enfermos de SIDA
6. Trasplantados
7. Contraindicaciones de la ficha técnica de los medicamentos

E.5 End points

E.5.1

Primary end point(s)

The main endpoints are:
a. Total plasma phytosterols and the following fractions: brassicasterol, beta-sitostanol, beta-sitosterol, campesterol, cholesterol, desmosterol, ergosterol, lanosterol, lathosterol and stigmasterol
b. GGT

Las variables principales son:
a. Fitoesteroles plasmáticos totales y las fracciones brasicaesterol, beta-sitostanol, beta-sitosterol, campesterol, colesterol, desmosterol, ergosterol, lanosterol, latosterol y stigmasterol
b. GGT

E.5.1.1

Timepoint(s) of evaluation of this end point

The main endpoints will be collected on days 0 (day of randomization) and on days 7, 14 and 21 after randomization

Las variables principales se recogerán los días 0 (día de randomización) y los días 7, 14 y 21 postradomización

E.5.2

Secondary end point(s)

Secondary endpoints collected are:
a. Liver parameters: alkaline phosphatase, ALT and total bilirubin
b. Safety parameters: triglycerides, platelet count and prothrombin time
c. Total amount of phytosterols administered in grams/Kg
d. Parameters of renal function: Creatinine
e. Inflammatory response parameters: C-reactive protein, interleukin-6, tumor necrosis factor and interleukin-10
f. Nutritional parameters: Albumin, Prealbumin and Lymphocytes

Las variables secundarias que se recogerán son:
a. Parámetros hepáticos: Fosfatasa alcalina, ALT y bilirrubina total
b. Parámetros de seguridad: Triglicéridos, recuento de plaquetas y tiempo de protrombina
c. Cantidad total de fitoesteroles administrdos en gramos/Kg
d. Parámetros de función renal: Creatinina
e. Parámetros de respuesta inflamatoria: Proteina C reactiva, interleucina-6, factor de necrosis tumoral e interleucina 10
f. Parámetros nutricionales: Albúmina, Prealbúmina y Linfocitos

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints will be collected on days 0 (day of randomization) and on days 7, 14 and 21 after randomization

Los valores plasmáticos como variables secundarias también se recogerán los días 0 (día de randomización) y los días 7, 14 y 21 postradomización .

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

Yes

E.6.4

Safety

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

emulsión lipídica con patrón oliva/soja

Olive/soy fatty acids

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

The trial will finished at the end of the last visit of the las patient included.

El ensayo finalizará después del seguimiento del último paciente reclutado.

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

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

2014-11-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-06

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

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