Clinical Trials Register

Summary
EudraCT Number:	2016-002936-34
Sponsor's Protocol Code Number:	iPROVE-O2-16
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-11-17
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

2016-002936-34

A.3

Full title of the trial

Effects on surgical site infection of an individualized perioperative openlung
ventilatory strategy with high versus conventional inspiratory oxygen fraction (iPROVEO2). A comparative, prospective, multicenter, randomized controlled trial.

Reducción de la infección de herida quirúrgica con una estrategia perioperatoria individualizada de ventilación de protección pulmonar con fracción inspiratoria de oxígeno elevada. Estudio comparativo, prospectivo, multicéntrico, aleatorizado y controlado.

A.3.1

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

Reduction of surgical wound infection breathing high concentrations of oxygen during anesthesia

Reducción de la infección de la herida quirúrgica respirando concentraciones altas de oxígeno durante la anestesia

A.3.2

Name or abbreviated title of the trial where available

iPROVE-O2

A.4.1

Sponsor's protocol code number

iPROVE-O2-16

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	Francisco Javier Belda Nacher
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	Anesthesiology Department Clinic Hospial of Valencia
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	Marina Soro Domingo
B.5.2	Functional name of contact point	Marina Soro Domingo
B.5.3	Address:
B.5.3.1	Street Address	Avd. Blasco Ibáñez, 17
B.5.3.2	Town/ city	Valencia
B.5.3.3	Post code	46010
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034961973847
B.5.5	Fax number	0034961973852
B.5.6	E-mail	soromarina@gmail.com

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	Oxígeno Medicinal Líquido Gasmedi 99,5% gas criogénico medicinal
D.2.1.1.2	Name of the Marketing Authorisation holder	GASMEDI
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	Medicinal gas, liquefied
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OXYGEN
D.3.9.1	CAS number	SUB14733MIG
D.3.9.2	Current sponsor code	O2
D.3.9.3	Other descriptive name	Medicinal Oxygen
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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	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	Oxygen compressed
D.2.1.1.2	Name of the Marketing Authorisation holder	GASMEDI
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	Medicinal gas, liquefied
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OXYGEN
D.3.9.1	CAS number	SUB14733MIG
D.3.9.2	Current sponsor code	O2
D.3.9.3	Other descriptive name	Medicinal Oxygen
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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

The study population will be patients who are scheduled for major abdominal (laparotomy and laparoscopic) surgery under general anaesthesia.

La población a estudio son pacientes que están programados para cirugia abdominal (laparotomía y laparoscópica), bajo anestesia general.

E.1.1.1

Medical condition in easily understood language

Patients who are scheduled for major abdominal surgery under general anaesthesia.

Pacientes programados para cirugía del abdomen con anestesia general.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

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 compare the efficacy of high vs. conventional FIO2 (inspiratory oxygen fraction) within a perioperative individualized ventilatory strategy to reduce the overall incidence of surgical site infection during the first 7 days after surgery in patients scheduled for abdominal surgery

Evaluar el efecto de la FIO2 (Fracción inspiratoria de Oxigeno) elevada con respecto a una convencional dentro de un manejo ventilatorio perioperatorio individualizado protector sobre el desenlace de infección de herida quirúrgica durante los primeros 7 días del postoperatorio en pacientes programados para cirugía abdominal.

E.2.2

Secondary objectives of the trial

To evaluate the composite of systemic complications experienced by the subjects in the first 7 postoperative days:
1) Anastomosis dehiscence; 2) Sepsis; 3) Septic shock; 4) Requirement for surgical re-intervention; 5) PONV; 6) Urinary infection; 7) Postoperative cognitive dysfunction; 8) Paralytic ileus; 9) Heart failure; 10) Myocardial ischemia; 11) Cardiac arrhythmias; 12) Renal failure;
To evaluate other secondary complications experienced by the subjects in the first 7 postoperative days:
13) Pulmonary complications: 14) Increased ICU and hospital length of stay (LOS); 15) ICU and hospital readmission in the first 30 postsurgical days; 16) Mortality within 30.

Evaluar la combinación de complicaciones sistémicas experimentadas por los sujetos en los primeros 7 días del postoperatorio:
1) La dehiscencia de anastomosis ; 2) La sepsis; 3) El shock séptico; 4) Necesidad de reintervención quirúrgica; 5) NVPO; 6) La infección urinaria; 7) la disfunción cognitiva postoperatoria; 8) El íleo paralítico; 9) La insuficiencia cardíaca; 10) la isquemia de miocardio; 11) Las arritmias cardíacas; 12) La insuficiencia renal;
Evaluar otras complicaciones secundarias experimentadas por los sujetos en los primeros 7 días del postoperatorio:
13) Las complicaciones pulmonares: 14) El aumento de la duración de la estancia en UCI y en el hospital (LOS); 15) UCI y reingreso hospitalario en los primeros 30 días post-quirúrgicas; 16) La mortalidad dentro de los 30.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Male or female patients ≥18 years old,
2) Body mass index (BMI) of <35 kg/m2
3) Scheduled for major abdominal (laparotomy and laparoscopic) surgery with an expected surgery duration of more than 2h.

1) Edad igual o superior a 18 años.
2) Índice de masa corporal (IMC) <35 kg/m2
2) Cirugía abdominal programada prevista de >2 horas de duración.

E.4

Principal exclusion criteria

1) < 18 years
2) Pregnant woman or in breast-feeding status
3) Body mass index (BMI) > 35 Kg/m2
4) Moderate or severe acute respiratory distress syndrome (ARDS; PaO2/ FIO2 < 200 mmHg)
5) Diagnosis of heart failure defined as a cardiac index < 2.5 ml/min/m2 or > 2.5 when ≥ 5μg/kg/min dobutamine is required, or suspected heart failure according to clinical signs (hypotension, oliguria, pulmonary edema) together with NT-proBNP > 13pg/ml,
6) Suspected intracranial hypertension (> 15 mmHg)
7) Presence of pneumothorax or giant bullae on a chest radiograph or computed tomography (CT)
8) Patients participating in another interventional study.

1) Edad menor de 18 años.
2) Mujeres embarazadas o en periodo de lactancia.
3) Índice de masa corporal (IMC) > 35 Kg/m2
4) Síndrome de distrés respiratorio agudo moderado o grave (PaO2/ FIO2 < 200mmHg).
5) Fallo cardiaco: IC < 2,5 L/min/m2 y/o requerimientos de soporte inotrópico previo a la cirugía. Sospecha por signos clínicos (hipotensión, oliguria, edema pulmonar) junto con NT-proBNP > 13 pg/ml)
6) Diagnóstico o sospecha de hipertensión intracraneal (> 15 mmHg).
7) Presencia de neumotórax. Presencia de bullas gigantes en la radiografía de tórax o en la tomografía axial computarizada (TAC).
8) Participación en otro protocolo de intervención experimental en el momento de la selección.

E.5 End points

E.5.1

Primary end point(s)

The appearance of surgical site infection , using the criteria set out by the Center for Disease Control (CDC) in study subjects within the first 7 postoperative days.

Aparición de infección de la herida quirúrgica, utilizando los criterios establecidos por el Centro para el Control de Enfermedades (CDC) de los sujetos de estudio dentro de los primeros 7 días del postoperatorio.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary end point will be taken 3 h after PACU/ICU admission and at 1, 2, 7, and 30 days after surgery.

3 h después de la admisión del paciente en la Unidad de Cuidados postoperatoria (PACU / UCI) y 1, 2, 7 y 30 días después de la cirugía.

E.5.2

Secondary end point(s)

The secondary end points are :
To evaluate the composite of systemic complications experienced by the subjects in the first 7 postoperative days:
1) Anastomosis dehiscence; 2) Sepsis; 3) Septic shock; 4) Requirement for surgical re-intervention; 5) PONV; 6) Urinary infection; 7) Postoperative cognitive dysfunction; 8) Paralytic ileus; 9) Heart failure; 10) Myocardial ischemia; 11) Cardiac arrhythmias; 12) Renal failure;
Other secondary end points are:
13) Pulmonary complications: 14) Increased ICU and hospital length of stay (LOS); 15) ICU and hospital readmission in the first 30 postsurgical days; 16) Mortality within 30.

Evaluar la combinación de complicaciones sistémicas en los primeros 7 días del postoperatorio:
1) La dehiscencia anastomosis; 2) La sepsis; 3) El shock séptico; 4) Necesidad de reintervención quirúrgica; 5) NVPO; 6) La infección urinaria; 7) la disfunción cognitiva postoperatoria; 8) El íleo paralítico; 9) La insuficiencia cardíaca; 10) la isquemia de miocardio; 11) Las arritmias cardíacas; 12) La insuficiencia renal;
Otros son:
13) Las complicaciones pulmonares: 14) El aumento de la duración de la estancia en UCI y en el hospital (LOS); 15) UCI y reingreso hospitalario en los primeros 30 días post-quirúrgicas; 16) La mortalidad dentro de los 30

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary end points will be taken 3 h after PACU/ICU admission and at 1, 2, 7, and 30 days after surgery, with a 180- and 365-day follow-up for mortality.

Las variables secundarias se tomarán 3 h después de la admisión de PACU / UCI y 1, 2, 7, y 30 días después de la cirugía, y tras 180 y 365 días de seguimiento se determinará la mortalidad.

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

Yes

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)

Yes

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

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

Last follow up (survival at day 365 post-surgery) of last randomized subject by phone call.

Seguimiento de la supervivencia a 365 días post-cirugía del último sujeto aleatorizado por LLamada de teléfono

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:

456

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

300

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

756

F.4.2

For a multinational trial

F.4.2.1

In the EEA

756

F.4.2.2

In the whole clinical trial

756

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

2017-01-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-07-19

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