Clinical Trials Register

Summary
EudraCT Number:	2016-004361-12
Sponsor's Protocol Code Number:	FER-CIT-2016-01
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:	2017-02-10
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-004361-12

A.3

Full title of the trial

Oxidative stress and extracellular nucleosomes in critically ill patients with acute kidney failure treated with continuous renal replacement therapies.
Effect of two anticoagulation strategies of the extracorporeal purification system in renal function recovery.

Estudio del estrés oxidativo y de los nucleosomas extracelulares en pacientes críticos con disfunción renal aguda en tratamiento con técnicas continuas de reemplazo renal.
Efecto de dos estrategias de anticoagulación del sistema de depuración extracorpóreo en la recuperación de la función renal.

A.3.1

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

A study to assess the effect in renal function recovery of two anticoagulation strategies (ways of making blood more fluent) in critically ill patients with acute kidney failure treated with continuous renal replacement therapies.

Estudio para evaluar el efecto en la recuperación de la función renal de dos estrategias de anticoagulación (formas de hacer la sangre más fluida) en pacientes críticos con insuficiencia renal aguda que necesitan tratamiento con terapias de reemplazo renal continuo.

A.4.1

Sponsor's protocol code number

FER-CIT-2016-01

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	Fernando Sánchez
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	Fernando Sánchez
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Hospital Universitario de La Plana
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	Fernando Sánchez
B.5.2	Functional name of contact point	Fernando Sánchez
B.5.3	Address:
B.5.3.1	Street Address	Sanz de Bremond 8, 1º
B.5.3.2	Town/ city	Castellon
B.5.3.3	Post code	12004
B.5.3.4	Country	Spain
B.5.4	Telephone number	34625978412
B.5.5	Fax number	34964399858
B.5.6	E-mail	sanchez_fermor@gva.es

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	Heparin sodium
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira Invicta, S.A.
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	Anticoagulant and preservative solution for blood
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Haemodialysis
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HEPARIN SODIUM
D.3.9.3	Other descriptive name	HEPARIN SODIUM
D.3.9.4	EV Substance Code	SUB02478MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 10
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

Acute renal failure (ARF).

Insuficiencia renal aguda.

E.1.1.1

Medical condition in easily understood language

Acute renal failure is the inability of the kidneys to perform their functions to purify and clean the blood, and in this setting we use machines to temporarily replace renal function.

La insuficiencia renal es la incapacidad de los riñones para realizar sus funciones de purificar y limpiar la sangre, por lo que se recurre a máquinas para sustituir temporalmente la función renal.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	PT
E.1.2	Classification code	10074746
E.1.2	Term	Renal replacement therapy
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10038436
E.1.2	Term	Renal failure acute
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To compare the effect on bio-incompatibility induced oxidative stress and systemic oxidative stress in critically ill patients with ARF using two anticoagulation strategies of the extracorporeal system in continuous renal replacement therapies (CRRT) (heparin vs citrate).
2. To compare the effect on extracellular levels of circulating nucleosomes in critically ill patients with ARF employing two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate).
3. To evaluate the clinical impact in terms of recovery of renal function in critically ill patients with ARF when two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate) are used.

1. Comparar el efecto en el estrés oxidativo inducido por bioincompatibilidad
así como el estrés oxidativo sistémico, en pacientes críticos con FRA al
emplear dos estrategias de anticoagulación del sistema extracorpóreo en las
TCRR (heparina vs citrato).
2. Comparar el efecto en los niveles de nucleosomas extracelulares circulantes
en pacientes críticos con FRA al emplear dos estrategias de anticoagulación
del sistema extracorpóreo en las TCRR (heparina vs citrato).
3. Evaluar el impacto clínico en términos de recuperación de la función renal,
en pacientes críticos con FRA cuando se utilizan dos estrategias de
anticoagulación del sistema extracorpóreo en las TCRR (heparina vs citrato).

E.2.2

Secondary objectives of the trial

1. To evaluate the differences in activation and in elimination of biomarkers of inflammation and infection with two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate).
2. To measure the mass transfer, clearance and impact on the plasma concentration of free radicals, antioxidants and circulating nucleosomes during the course of therapy and compare the differences between the two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate).
3. To compare the final result, in terms of stay and survival in critically ill patients with ARF when two anticoagulation strategies of the extracorporeal system CRRT (heparin vs citrate) are used.

1. Evaluar las diferencias de activación y eliminación de marcadores de
inflamación y de infección cuando se utilizan dos estrategias de
anticoagulación del sistema extracorpóreo en las TCRR (heparina vs citrato).
2. Medir la transferencia de masas, aclaramiento e impacto en la concentración
plasmática de radicales libres y antioxidantes durante el curso de la terapia y
comparar las diferencias entre las dos estrategias de anticoagulación del
sistema extracorpóreo en las TCRR (heparina vs citrato).
3. Comparar el resultado final, en términos de estancia y supervivencia, en
pacientes críticos con FRA cuando se utilizan dos estrategias de
anticoagulación del sistema extracorpóreo en las TCRR (heparina vs citrato).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Adult intensive care patients (age ≥ 18 years) admitted to the ICU with ARF requiring treatment with continuous renal replacement technique.
• Patients able to accept being included in the study by signing the Informed Consent (IC). If the patient can not give consent, family consent is requested and, by default, the opinion of the person of trust or designated decision, if present. If there is no family present, trusted person or legal representative designated, the possibility of deferred consent is not contemplated. In this case the patient will not be included in the study.

• Hombres y mujeres mayores de 18 años ingresados en UCI con FRA que requiera tratamiento con técnica de reemplazo renal continuo.
• Pacientes capaces de aceptar ser incluidos en el estudio mediante firma del Consentimiento Informado (CI). Si el paciente no puede dar su consentimiento, se solicitará el consentimiento de los familiares y, por defecto, la opinión de la persona de confianza o designada para la toma de decisiones, si están presentes. Si no hay familia presente, o persona de confianza designada, se contempla la posibilidad del consentimiento diferido. En este caso el paciente no será incluido en el estudio.

E.4

Principal exclusion criteria

• Age under 18 or over 80 years.
• Pregnancy and/or lactation.
• Terminal diseases or life expectancy lower than 48 hours.
• Increased risk of bleeding (defined as platelet count less than 40x109 / L, partial thromboplastin time -TTPA- over 60 seconds, prothrombin time international normalized ratio -PT-INR- greater than 2.0 or recent major bleeding).
• Need of systemic anticoagulation therapy.
• Contraindication for heparin.
• Heparin-induced Thrombocytopenia (HIT).
• Dialysis in the 24 hours prior to inclusion.
• hypercalcemia (> 3 mmol / L).
• Severe Hepatitis (GOT or GPT> 1000 IU / L).
• Cirrhosis.
• Inclusion in another research protocol.

• Edad menor de 18 años o mayor de 80 años.
20 v.1 01/10/2016
• Embarazo o lactancia.
• Pacientes enfermedades terminales o con expectativa de vida menor de 48 horas.
• Riesgo aumentado de sangrado (definido como recuento de plaquetas inferior a 40x109/L, tiempo de tromboplastina parcial activada -TTPA- mayor de 60 segundos, tiempo de protrombina-ratio normalizado internacional -PT-INRmayor de 2.0 o sangrado mayor reciente).
• Necesidad de anticoagulación sistémica terapéutica.
• Contraindicación para el uso de heparina.
• Trombopenia inducida por heparina (HIT).
• Diálisis en las 24 horas previas a su inclusión.
• Hipercalcemia (>3 mmol/L).
• Hepatitis grave (GOT o GPT > 1000 UI/L).
• Cirrosis.
• Inclusión en otro protocolo de investigación.

E.5 End points

E.5.1

Primary end point(s)

• Lenght of renal replacement therapy (RRT).
• Renal function at discharge from the ICU and hospital.

• Agregado días con terapia de remplazo renal (TRR)
• Función renal al alta de la UCI y del Hospital.

E.5.1.1

Timepoint(s) of evaluation of this end point

• Definitive discontinuation of RRT.
• ICU and hospital discharge.

• Desconexión definitiva de la TCRR.
• Alta de UCI y alta del hospital.

E.5.2

Secondary end point(s)

• Plasma clearance of free radicals and inflammation biomarkers.
• Changes in plasma concentration of free radicals and inflammation biomarkers.
• Sieving coefficient of free radicals and inflammation biomarkers.
• Lenght of stay in ICU.
• Lenght of stay in hospital.
• ICU mortality.
• Hospital mortality.

• Aclaramiento plasmático de los radicales libres y de los biomarcadores de inflamación.
• Variación en la concentración plasmática de los radicales libres y de los marcadores de inflamación.
• Coeficiente de cribado de los radicales libres y de los marcadores de inflamación.
• Duración de la estancia en la UCI.
• Duración de la estancia en el hospital.
• Mortalidad en la UCI.
• Mortalidad hospitalaria.

E.5.2.1

Timepoint(s) of evaluation of this end point

• 24 hours after de initiation of the therapy.
• Definitive discontinuation of RRT.
• ICU and hospital discharge.

• A las 24 horas del inicio de la terapia.
• Desconexión definitiva de la TCRR.
• Alta de UCI y alta del hospital.

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

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Citrato Trisodico

Trisodium Citrate

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

LVLS

Última visita del último sujeto

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

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients admited ICUs are often unable of providing consent personally.

Es frecuente que los pacientes admitidos en UCI no sean capaces de dar su consentimiento personalmente.

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

2017-03-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-02

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