Clinical Trials Register

Summary
EudraCT Number:	2014-000449-65
Sponsor's Protocol Code Number:	Desprobioxa
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:	2014-04-25
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

2014-000449-65

A.3

Full title of the trial

PILOT STUDY OF the EFFECTIVENESS of PROBIOTICS and LACTITOL for the INTESTINAL Decolonization of PEOPLE CARRIERS of Klebsiella pneumoniae producers of carbapenemase OXA-48 TYPE: STUDIO DESPROBIOXA

ESTUDIO PILOTO DE EFICACIA DE LACTITOL Y PROBIÓTICOS PARA LA DESCOLONIZACIÓN INTESTINAL DE PERSONAS PORTADORAS DE KLEBSIELLA PNEUMONIAE PRODUCTORAS DE CARBAPENEMASA TIPO OXA-48: ESTUDIO DESPROBIOXA

A.3.1

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

PILOT STUDY OF the EFFECTIVENESS of PROBIOTICS and LACTITOL for the INTESTINAL Decolonization of PEOPLE CARRIERS of Klebsiella pneumoniae producers of carbapenemase OXA-48 TYPE.

ESTUDIO PILOTO DE EFICACIA DE LACTITOL Y PROBIÓTICOS PARA LA DESCOLONIZACIÓN INTESTINAL DE PERSONAS PORTADORAS DE KLEBSIELLA PNEUMONIAE PRODUCTORAS DE CARBAPENEMASA TIPO OXA-48

A.3.2

Name or abbreviated title of the trial where available

Desprobioxa

A.4.1

Sponsor's protocol code number

Desprobioxa

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	Fundacion para La Investigación Biomédica Hospital Universitario La Paz (FIBHULP)
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	Hospital Universitario La Paz
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	FIBHULP
B.5.2	Functional name of contact point	Maria Posada
B.5.3	Address:
B.5.3.1	Street Address	Paseo de la Castellana 261
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28046
B.5.3.4	Country	Spain
B.5.4	Telephone number	34912071876
B.5.5	Fax number	34912071876
B.5.6	E-mail	maria.posada@idipaz.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	Emportal
D.2.1.1.2	Name of the Marketing Authorisation holder	Angelini Farmacéutica, 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	Powder for oral solution in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AC1L3M5J
D.3.9.1	CAS number	81025-04-9
D.3.9.3	Other descriptive name	LACTITOL MONOHYDRATE
D.3.9.4	EV Substance Code	SUB12097MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
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	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	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	Infloran Berna
D.2.1.1.2	Name of the Marketing Authorisation holder	Desma Laboratorio
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	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LACTOBACILLUS ACIDOPHILUS
D.3.9.1	CAS number	68333-16-4
D.3.9.3	Other descriptive name	LACTOBACILLUS ACIDOPHILUS
D.3.9.4	EV Substance Code	SUB14308MIG
D.3.10	Strength
D.3.10.1	Concentration unit	CFU/g colony forming unit(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000000
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LACTOBACILLUS BIFIDUS
D.3.9.1	CAS number	8500008-73-3
D.3.9.3	Other descriptive name	LACTOBACILLUS BIFIDUS, LYOPHILIZED
D.3.9.4	EV Substance Code	SUB14311MIG
D.3.10	Strength
D.3.10.1	Concentration unit	CFU/g colony forming unit(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000000
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	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

Intestinal Decolonization

Descolonizacion intestinal

E.1.1.1

Medical condition in easily understood language

Intestinal Decolonization

Descolonizacion intestinal

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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	10069718
E.1.2	Term	Bacterial colonization
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the effectiveness of the combination of lactitol and probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum), administered orally to achieve intestinal decolonization of KP-OXA-48 in people after 6 weeks of completing treatment (Sustained Response) .

Evaluar la eficacia de la combinación de lactitol y probióticos (Lactobacillus acidophilus y Bifidobacterium bifidum), administrados por vía oral, para lograr la descolonización intestinal de KP-OXA-48 en personas portadoras a las 6 semanas del fin del tratamiento (Repuesta Sostenida).

E.2.2

Secondary objectives of the trial

?Evaluate the effectiveness of lactitol and probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum ) administered orally for intestinal decolonization of KP- OXA -48 in people at the time of the end of treatment ( End of treatment Response) and 3 weeks after end of treatment ( Short-term response ) .
? To evaluate the safety and tolerability of the combination of lactitol and probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum ) orally administered to people with KP- OXA -48 .
? Analyze the effect of the combination of lactitol and probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum ) administered orally on intestinal microbiota of carriers of KP- OXA -48 .
? Evaluate the time from the start of treatment with lactitol and probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum ) to intestinal decolonization in those patients who achieved sustained response .

?Evaluar la eficacia de lactitol y probióticos (Lactobacillus acidophilus y Bifidobacterium bifidum), administrados por vía oral, para la descolonización intestinal de KP-OXA-48 en personas portadoras, en el momento del fin del tratamiento (Respuesta de fin de tratamiento) y a las 3 semanas del fin del tratamiento (Respuesta a corto plazo) .
?Evaluar la seguridad y tolerabilidad de la combinación de lactitol y probióticos (Lactobacillus acidophilus y Bifidobacterium bifidum) administrados por vía oral a personas portadoras de KP-OXA-48.
?Analizar el efecto de la combinación de lactitol y probióticos (Lactobacillus acidophilus y Bifidobacterium bifidum) administrados por vía oral sobre la microbiota intestinal de personas portadoras de KP-OXA-48.
?Evaluar el tiempo desde el inicio del tratamiento con lactitol y probióticos (Lactobacillus acidophilus y Bifidobacterium bifidum) hasta la descolonización intestinal en aquellos pacientes en que se consigue respuesta sostenida.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Men and women between 18 and 75 years
? Have signed the informed consent to participate.
? have evidence of intestinal colonization by KP-OXA-48 during the period of screening.
? Start of intestinal colonization by KP-OXA-48, ? 6 months of starting treatment
? Absence of exclusion criteria

? Hombres y mujeres entre 18 y 75 años
? Haber firmado el consentimiento informado para participar.
? Disponer de evidencia de colonización intestinal por KP-OXA-48 durante el periodo de screening.
? Inicio de colonización intestinal por KP-OXA-48, ? 6 meses al inicio del tratamiento
? Ausencia de criterios de exclusión

E.4

Principal exclusion criteria

?Be hospitalized for an acute process at the time of inclusion
? Take antibiotics ( oral , intramuscular or intravenous ) at the time of inclusion
? Having diarrhea in the two weeks prior to the inclusion
? baseline electrolyte abnormalities requiring supplementation : Hypokalemia (K <3 mEq / L ), hypomagnesemia (Mg <1.8 mEq / L ), hypocalcemia (Ca < 8mg/dL )
? Suffering from digestive diseases : Crohn's disease, ulcerative colitis , celiac disease, irritable bowel syndrome , intestinal resection, colostomies .
? Neutropenia ( neutrophil count < 1.00 x 10 3 / uL ) or other situations of severe immunosuppression , including continued use of systemic steroids (at least 1mg/kg/day of prednisone or equivalent for more than 1 month) and other forms of pharmacological immunosuppression deemed by the investigator
? Diabetes mellitus poorly controlled ( HgA1c > 8 mmol / mol )
? Taking antisecretory inhibitors, proton pump or anti -H2
? advanced chronic renal failure ( GFR < 30 ml / min)
? Being a carrier of endovascular prosthetic devices , including long-term central catheters
? Having significant valvulopathy on the opinion of the investigator .
? Surgical intervention of gastrointestinal tract in the last three months
? Treatment with systemic corticosteroids or immunosuppressive
?Allergy or intolerance to lactose or lactitol or Infloran .

? Encontrarse hospitalizado por un proceso agudo en el momento de la inclusión
? Precisar tratamiento antibiótico por vía sistémica (oral, intramuscular o intravenoso) en el momento de la inclusión
? Padecer diarrea en las dos semanas previas a la inclusión
? Alteraciones hidroelectrolíticas basales que requieran suplementación: Hipopotasemia ( K < 3 mEq/L); Hipomagnesemia (Mg < 1,8 mEq/L); Hipocalcemia (Ca < 8mg/dL)
? Padecer enfermedades digestivas: enfermedad de Crohn, colitis ulcerosa, enfermedad celiaca, sindrome de colon irritable, resección intestinal, colostomias.
? Neutropenia (neutrófilos < 1,00 x 10 3 / µL) u otras situaciones de inmunosupresión grave, incluyendo uso de mantenido de esteroides sistémicos (al menos 1mg/Kg/día de prednisona o equivalente durante más de 1 mes) y otras formas de inmunosupresión farmacológica que a juicio del investigador
? Diabetes mellitus mal controlada (HgA1c > 8 mmol/mol)
? Toma de antisecretores: inhibidores de la bomba de protones o anti-H2
? Insuficiencia renal crónica avanzada (FGE < 30 ml/min)
? Ser portador de dispositivos protésicos endovasculares, incluyendo catéteres centrales de larga duración
? Padecer valvulopatía significativa a juicio del investigador.
? Intervención quirúrgica de aparato digestivo en los últimos tres meses
? Precisar tratamiento con corticoides sistémicos o inmunosupresores
Alergia o intolerancia a lactosa o lactitol o Infloran.

E.5 End points

E.5.1

Primary end point(s)

? Response to treatment: if the presence of KP-OXA-48 in fecal / rectal sample was not detected at the end of treatment visit.
? Short Term Response: If the presence of KP-OXA-48 is not detected in rectal / fecal sample three weeks after treatment ended (V7) or any visits since the end of treatment
? Long-term Response (primary endpoint) in patients with short-term response that 6 weeks after the end of treatment visit theOXA-48 KP is not detected

? Respuesta de fin de tratamiento: si no se detecta la presencia de KP-OXA-48 en muestra fecal/rectal en la visita de fin de tratamiento
? Respuesta a corto plazo: si no se detecta la presencia de KP-OXA-48 en muestra rectal/fecal a las tres semanas de haber finalizado tratamiento (V7) ni en ninguna de las visitas desde el fin de tratamiento
? Respuesta a largo plazo (variable principal): en aquellos pacientes con respuesta a corto plazo en los que no se detecte la presencia de KP-OXA-48 a las 6 semanas de haber finalizado el tratamiento (V8)

E.5.1.1

Timepoint(s) of evaluation of this end point

V4: Visit End of treatment (Day 21 + / - 2)
V7: Follow up Visit S3 (Day 42 + / - 2)
V8: End of Follow up visit S4 (Day 63 + / - 2)

V4: Visita de Fin de Tratamiento T3 (Día 21 +/- 2)
V7: Visita de Seguimiento S3 (Día 42 +/- 2)
V8: Visita de Fin de Seguimiento S4 (Día 63 +/- 2)

E.5.2

Secondary end point(s)

Safety and tolerability
Microbiological determinations

Variables de seguridad y tolerabilidad
Determinaciones microbiológicas

E.5.2.1

Timepoint(s) of evaluation of this end point

During all the study

Durante todo el estudio

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Un unico brazo

Single arm

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

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

Ultima visita del ultimo 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
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-05-08

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

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