Clinical Trials Register

Summary
EudraCT Number:	2021-006908-32
Sponsor's Protocol Code Number:	PNEUMONOVA
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:	2022-02-10
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

2021-006908-32

A.3

Full title of the trial

Intrapulmonary penetration of ceftolozane / tazobactam and ceftazidime / avibactam administered in continuous infusion in critically ill patients with nosocomial pneumonia

PENETRACIÓN INTRAPULMONAR DE CEFTOLOZANO/TAZOBACTAM Y CEFTAZIDIME/AVIBACTAM ADMINISTRADOS EN INFUSIÓN CONTINUA EN PACIENTES CRÍTICOS CON NEUMONÍA NOSOCOMIAL

A.3.1

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

Pulmonary beta-lactam levels in ICU pneumonia

Niveles intra-pulmonares de betalactámicos en neumonías en UCI

A.3.2

Name or abbreviated title of the trial where available

Beta-lactam monitoring in continuous infusion in nosocomial pneumonia

Monitorización de betalactámicos en perfusión continua en neumonía nosocomial

A.4.1

Sponsor's protocol code number

PNEUMONOVA

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	Sonia Luque Pardos
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	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	Sonia Luque Pardos
B.5.2	Functional name of contact point	Sonia Luque Pardos
B.5.3	Address:
B.5.3.1	Street Address	Passeig Marítim de la Barceloneta, 25, 29
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08003
B.5.3.4	Country	Spain
B.5.6	E-mail	SLuque@parcdesalutmar.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	ZAVICEFTA 2 G/0,5 G POLVO PARA CONCENTRADO PARA SOLUCION PARA PERFUSION
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Ireland Pharmaceuticals
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	ceftazidima/avibactam
D.3.2	Product code	EMA/369737/2020
D.3.4	Pharmaceutical form	Powder for concentrate for solution 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	Ceftazidime
D.3.9.1	CAS number	73547-61-2
D.3.9.3	Other descriptive name	CEFTAZIDIME SODIUM
D.3.9.4	EV Substance Code	SUB130849
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Avibactam
D.3.9.1	CAS number	689293-68-3
D.3.9.3	Other descriptive name	AVIBACTAM SODIUM
D.3.9.4	EV Substance Code	SUB179984
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	0.5
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	Zerbaxa 1 g/0,5 g polvo para concentrado para solución para perfusión
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V
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	ceftolozano\tazobactam
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CEFTOLOZANE
D.3.9.1	CAS number	689293-68-3
D.3.9.3	Other descriptive name	CEFTOLOZANE SULFATE
D.3.9.4	EV Substance Code	SUB167761
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	1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TAZOBACTAM
D.3.9.1	CAS number	689293-68-3
D.3.9.2	Current sponsor code	EU/1/15/1032/001
D.3.9.3	Other descriptive name	TAZOBACTAM SODIUM
D.3.9.4	EV Substance Code	SUB04682MIG
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	0.5
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

Nosocomial pneumonia

Neumonía nosocomial

E.1.1.1

Medical condition in easily understood language

Nosocomial pneumonia

Neumonía nosocomial

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10052596
E.1.2	Term	Nosocomial pneumonia
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

To evaluate and compare the intrapulmonary penetration (into the epithelial lining fluid) of ceftazidime/avibactam and ceftolozane/tazobactam administered as a continuous infusion in the critically ill patient with nosocomial pneumonia. Lung penetration is defined as the ratio of AUC24h in ELF to AUC24h in plasma.

Evaluar y comparar la penetración intrapulmonar (en el líquido de revestimiento epitelial) de ceftazidima/avibactam y ceftolozano/tazobactam administrados en perfusión continua en el paciente crítico con neumonía nosocomial. La penetración en pulmón se define como la ratio entre el AUC24h en ELF/ AUC24h en plasma.

E.2.2

Secondary objectives of the trial

plasma and LRE in order to assess whether plasma exposure can be a surrogate marker of pulmonary exposure.
5. To analyse patient factors that may influence the PK of plasma C/A and C/T and their penetration into LRE.
6. To describe the clinical efficacy and mortality of patients treated with C/A and C/T.

1. Evaluar el porcentaje de pacientes críticos con neumonía nosocomial que alcanzan unos niveles en LRE que superan el valor de la CMI de los BGN-MDR más prevalentes en la neumonía nosocomial
2. Diseñar un modelo farmacocinético poblacional en plasma y LRE de C/A y C/T en el paciente crítico.
3. Realizar simulaciones de Montecarlo con los dos modelos farmacocinéticos poblacionales de C/A y C/T para diseñar regímenes posológicos óptimos (eficaces y seguros) para distintos microorganismos con distinto perfil de sensibilidad antimicrobiana.
4. Analizar si existe una correlación lineal entre las concentraciones individuales de C/A y C/T en plasma y en LRE con el fin de valorar si la exposición en plasma puede ser un marcador subrogado de la exposición pulmonar.
5. Analizar los factores de los pacientes que pueden influir en la PK de C/A y C/T en plasma y en su penetración en LRE
6. Describir la eficacia clínica y la mortalidad de los pacientes tratados con C/A y C/T

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients of both sexes over 18 years of age.
2. Diagnosis of pneumonia will be based on the following clinical and radiological criteria and should be made within 24 hours prior to receiving the study drug:
a. purulent tracheal secretions with at least one of the other clinical criteria.
b. (fever [>38ºC], or hypothermia [<34ºC],
c. >10,000 or <4,500 leukocytes per µL, or >15% immature neutrophils,
d. Presence of new or progressive infiltrates on chest X-ray or CT scan whenever suggestive of bacterial pneumonia.

The diagnosis of ventilator-associated pneumonia (VAP) shall be made when the patient has been ventilated for at least 48 hours prior to the onset of pneumonia.

1. Pacientes de ambos sexos mayores de 18 años de edad
2. Diagnóstico de neumonía estará basado en los siguientes criterios clínicos y radiológicos y deberá hacerse durante 24 horas antes de recibir el fármaco a estudio:
a. secreciones traqueales purulentas con al menos uno de los otros criterios clínicos
b. (fiebre [>38ºC], o hipotermia [<34ºC],
c. >10.000 ó < 4.500 leucocitos por µL, ó >15% de neutrófilos inmaduros,
d. Presencia de infiltrados nuevos o progresivos en la radiografía o TAC de tórax siempre que sean sugestivos de neumonía bacteriana.

El diagnóstico de neumonía asociada a ventilador (NAV) se realizará cuando el paciente haya estado ventilado al menos 48 horas antes de la aparición de la neumonía.

E.4

Principal exclusion criteria

1. Pregnant or actively breastfeeding patients.
2. Patients with allergy or intolerance to ß-lactam antibiotics.
3. Patients whose baseline condition contraindicates fibrobronchoscopy (at the discretion of the treating physician).
4. Patients under treatment with any renal replacement therapy or extracorporeal support.

1. Pacientes embarazadas o en periodo de lactancia activa.
2. Pacientes con alergia o intolerancia a los antibióticos ß-lactámicos
3. Pacientes cuya situación basal contraindique la realización de una fibrobroncoscopia (criterio del médico tratante)
4. Pacientes en tratamiento con cualquier terapia renal sustitutiva o soporte extracorpóreo.

E.5 End points

E.5.1

Primary end point(s)

- Clinical response

- Clinical cure. Disappearance of ALL symptoms and signs of infection present prior to initiation of treatment.
- Failure. No change or worsening of symptoms and signs of infection present before starting treatment.
- Recurrence. Improvement or disappearance of symptoms and signs of infection present before starting treatment with subsequent reappearance or worsening during follow-up.

- Microbiological response

- Eradication. Absence of growth of the causative micro-organism present before starting treatment.
- Persistence. Isolation of the same microorganism after completing treatment without having achieved eradication.
- Recurrence. Isolation of the same micro-organism after completion of treatment after apparent eradication has been achieved.
- Superinfection. Isolation of a pathogenic micro-organism different from the causative agent of the original infection.

- Respuesta clínica

- Curación clínica. Desaparición de TODOS los síntomas y signos de infección presentes antes de iniciar el tratamiento.
- Fracaso. No se modifican o empeoran los síntomas y signos de infección presentes antes de iniciar el tratamiento
- Recurrencia. Mejoría o desaparición de los síntomas y signos de infección presentes antes de iniciar el tratamiento con posterior reaparición o empeoramiento durante el seguimiento.

- Respuesta microbiológica

- Erradicación. Ausencia de crecimiento del microorganismo causal presente antes de iniciar el tratamiento.
- Persistencia. Aislamiento del mismo microorganismo tras completar el tratamiento sin haber alcanzado la erradicación.
- Recurrencia. Aislamiento del mismo microorganismo tras completar el tratamiento tras haber alcanzado una aparente erradicación.
- Superinfección. Aislamiento de un microorganismo patógeno diferente al agente causal de la infección original.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days

30 días

E.5.2

Secondary end point(s)

- Mortality
- During antibiotic treatment.

- Development of intra-treatment resistance

- Increase in the MIC of the micro-organism initially isolated for the study drug.

- Mortalidad
- Durante el tratamiento antibiótico.

- Desarrollo de resistencias intratratamiento

- Aumento de la CMI del microorganismo aislado inicialmente para el fármaco de estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

Hospital Discharge

Alta Hospitalaria

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

E.6.6

Pharmacokinetic

Yes

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

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

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

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. 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)

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

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

ICU patients

Pacientes UCI

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

2022-07-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-06-09

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