Clinical Trials Register

Summary
EudraCT Number:	2013-000586-37
Sponsor's Protocol Code Number:	BACSARM
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:	2013-05-16
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

2013-000586-37

A.3

Full title of the trial

Randomized multicenter study to assess efficacy of Daptomycin plus Fosfomycin versus Daptomycin monotherapy for treatment of methicillin resistant Staphylococcus aureus bacteremia in hospitalized patients.

Estudio aleatorizado, multicentrico que compara la eficacia de la combinación de Daptomicina y Fosfomicina frente a la Daptomicina en monoterapia para el tratamiento de la bacteriemia por Staphylococcus aureus resistente a la meticilina en pacientes hospitalizados.

A.3.1

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

Randomized multicenter study to compare survival and clinical improvement of methicillin resistant Staphylococcus aureus bacteremia in hospitalized patients when they are treated with combination of Daptomycin plus Fosfomycin versus Daptomycin alone.

Ensayo Clínico randomizado para comparar la supervivencia y la respuesta clínica de la bacteriemia por Staphylococcus aureus resistente a meticilina en pacientes hospitalizados cuando se tratan con la combinación de Daptomicina más Fosfomicina frente al tratamiento con Daptomicina sola.

A.4.1

Sponsor's protocol code number

BACSARM

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	Miquel Pujol Rojo (Infectious Diseases Service-Hospital Universitari de Bellvitge-IDIBELL)
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	Fondo de Investigaciones Sanitarias (FIS)-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	Miquel Pujol Rojo (Infectious diseases service)
B.5.2	Functional name of contact point	Hospital Universitario de Bellvitge
B.5.3	Address:
B.5.3.1	Street Address	Feixa Llarga s/n
B.5.3.2	Town/ city	Hospitalet Llobregat/Barcelona
B.5.3.3	Post code	08907
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349326073837383
B.5.5	Fax number	+349326072747274
B.5.6	E-mail	mpujol@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	FOSFOCINA
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratorios ERN
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.3.1	Product name	FOSFOMICYN
D.3.4	Pharmaceutical form	Powder and solvent for 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	FOSFOMYCIN
D.3.9.1	CAS number	23155-02-4
D.3.9.4	EV Substance Code	SUB07797MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
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	CUBICIN
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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 and solution for solution for injection
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	DAPTOMYCIN
D.3.9.1	CAS number	103060-53-3
D.3.9.4	EV Substance Code	SUB06910MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
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: 3
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	CUBICIN
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
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 and solution for solution for injection
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	DAPTOMYCIN
D.3.9.1	CAS number	103060-53-3
D.3.9.4	EV Substance Code	SUB06910MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
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

Methicillin resistant Staphylococcus aureus bacteremia, complicated or uncomplicated

Bacteriemia por Staphylococcus aureus resistente a meticilina complicada o no complicada.

E.1.1.1

Medical condition in easily understood language

Severe infection by Methicillin resistant Staphylococcus aureus

Infección grave por Staphylococcus aureus resistente a meticilina

E.1.1.2

Therapeutic area

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

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 show a higher response at 6th week of end of therapy (EOT visit)on methicillin-resistant Staphylococcus aureus bacteremia when it's treated with a combination of Daptomycin plus Fosfomycin versus monotherapy with Daptomycin.

Demostrar la superioridad en la respuesta al tratamiento en la semana 6 post finalización de éste (visita EOT), al tratar la bacteriemia por Staphylococcus aureus resistente a meticilina con una combianción de Daptomicina y Fosfomicina frente a la monoterapia con Daptomicina.

E.2.2

Secondary objectives of the trial

To compare clinical efficacy of Daptomycin plus Fosfomicyn versus Daptomycin monotherapy on patients with methicillin-resistant Staphylococcus aureus bacteremia at the end of therapy (TOC visit).
To assess security of Daptomycin plus Fosfomycin versus Daptomycin monotherapy on patients with methicillin-resistant Staphylococcus aureus bacteremia.
To assess overall mortality in both treatment groups during the study period.
To asses frequency of persistant or recurrent bacteremia in both groups
To determine emergency of Daptomycin or Fosfomycin resistence during therapy in both groups

Comparar la eficacia clínica de la combinación de daptomicina y Fosfomicina frente a Daptomicina en monoterapia en pacientes con bacteriemia por Staphylococcus aureus resistente a meticilina, al finalizar el tratamiento antibiótico (TOC)
Evaluar la seguridad de la combinación de daptomicina y Fosfomicina comparada con Daptomicina en monoterapia en apceintes con bacteriemia por Staphylococcus aureus resistente a meticilina.
Evaluar la mortalidad global en los dos grupos de tratamiento durante el periodo de estudio.
Evaluar la frecuencai de bacteriemia persistente o recurrente en los 2 grupos.
Determinar la emergencia de resistencia a Daptomicina o Fosfomicina en los 2 grupos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with at least 1 positive blood culture to meticillin-resistant Staphylococcus aureus within the first 72h to the recruitment
2. Adult patients, equal or older than 18 years
3. Mandatory use of contraceptive for fertile women during the study period and the next 6 months to finalization
4.Signed informed consent

1. Pacientes con 1 o más hemocultivos positivos para SARM obtenidos dentro de las 72 horas previas a la inclusión en el estudio en un contexto sugestivo de infección.
2. Edad igual o superior a 18 años.
3. En caso de pacientes mujeres en edad fértil, éstas deberán seguir un tratamiento contraceptivo adecuado, según criterio del clínico, durante el estudio y hasta 6 meses después de finalizado.
4. El sujeto o su representante legal otorgan el consentimiento informado voluntariamente.

E.4

Principal exclusion criteria

1. Polymicrobial bacteremia
2. Neumonia associated to bacteremia
3. Severe clinical status with survival expectancy inferior to 24h.
4. Liver function impairment (grade C Child-Pugh)
5. Allergy to Daptomycin or Fosfomycin.
6. Positive pregnant test.
7. The clinical status required an antibiotic with MRSA activity and do not allow to stop it during the study.
8. Patient included in another clinical trial.
9. Eosinophilic pneumonia history.

1. Bacteriemia polimicrobiana.
2. Pacientes con neumonía asociada, como origen de la bacteriemia.
3. Situación clínica comprometida con una expectativa de vida ? a 24h.
4. Deterioro de la función hepática grave (grado C de Child-Pugh)
5. Alergia a Daptomicina o Fosfomicina.
6. Test de embarazo positivo en la visita basal o mujer en periodo de lactancia.
7. Paciente que por la condición clínica requiere realizar un tratamiento antibiótico con actividad frente a SARM, de forma concomitante al antibiótico del estudio (p.e Rifampicina, Cotrimoxazol, Clindamicina)
Se acepta el uso tópico de antibióticos o antisépticos con actividad anti SARM
8. Paciente que este participando en otro ensayo clínico de tratamiento.
9. Antecedentes de neumonía eosinofílica diagnosticada o sospechada.

E.5 End points

E.5.1

Primary end point(s)

Therapy response (defined as clinical and microbiological response)

Respuesta al tratamiento (definida como respuesta clinica y microbiologica)

E.5.1.1

Timepoint(s) of evaluation of this end point

At 6 week post-therapy

A las 6 semanas de finalizado el tratamiento.

E.5.2

Secondary end point(s)

1. Therapy response (defined as clinical and microbiological response)
2. Mortality
3. Severe adverse effects
4. Persistent bacteremia (defined as a positive blood culture at day 7)
5. Recurrent bacteremia (defined as a positive blood culture with a previous negative sample)

1. Respuesta al tratamiento (definida como respuesta clinica y microbiologica)
2. Mortalidad
3. Efectos adversos graves
4. Bacteriemia persistente (definida como un hemocultivo positivo el dia 7 de iniciado el tratamiento)
5. bacteriemia recurrente (definido como un hemocultivo positivo cuando existia uno previo negativo)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. At end of therapy (it could be at week 2 or 4)
2. At the end of the study
3. At the end of the study
4. At the end of the study
5. At the end of the study

1. Al final del tratamiento (que puede ser a la semana 2 o a la semana 4)
2. Al final del estudio
3. Al final del estudio
4. Al final del estudio
5. Al final del 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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Daptomicina

Daptomycin

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Yes

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

Las visit of the last subject (LVLS)

Última visita del último sujeto incluido en el estudio

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:

126

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

Yes

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

206

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

2013-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-11

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

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