Clinical Trials Register

Summary
EudraCT Number:	2018-002525-35
Sponsor's Protocol Code Number:	ICUConservativeO2
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-02-09
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-002525-35

A.3

Full title of the trial

Conservative vs conventional oxygen administration in critically ill patients: effects on ICU mortality. A multicentre randomized open label clinical trial.

Somministrazione di ossigeno conservativa vs convenzionale nel paziente critico: effetti sulla mortalità in terapia intensiva. Uno studio clinico multicentrico randomizzato controllato in aperto.

A.3.1

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

Conservative vs conventional oxygen administration in critically ill patients: effects on ICU mortality. A multicentre randomized open label clinical trial.

Somministrazione di ossigeno conservativa vs convenzionale nel paziente critico: effetti sulla mortalità in terapia intensiva. Uno studio clinico multicentrico randomizzato controllato in aperto.

A.3.2

Name or abbreviated title of the trial where available

Conservative vs conventional oxygen administration in critically ill patients

Somministrazione di ossigeno conservativa vs convenzionale nel paziente critico

A.4.1

Sponsor's protocol code number

ICUConservativeO2

A.5.4

Other Identifiers

Name:

ICUConservativeO2

Number:

ICUConservativeO2

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	AZIENDA OSPEDALIERO-UNIVERSITARIA DI MODENA
B.1.3.4	Country	Italy
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	ESICM
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Azienda Ospedaliero-Universitaria di Modena
B.5.2	Functional name of contact point	Clinical Trial Quality Team
B.5.3	Address:
B.5.3.1	Street Address	via del Pozzo 71
B.5.3.2	Town/ city	Modena
B.5.3.3	Post code	41124
B.5.3.4	Country	Italy
B.5.4	Telephone number	0594225868
B.5.5	Fax number	0594224369
B.5.6	E-mail	ricercainnovazione@policlinico.mo.it

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	OSSIGENO CER MEDICAL - GAS MEDICINALE CRIOGENICO CONTENITORE CRIOGENICO FISSO DA 5.000 LITRI
D.2.1.1.2	Name of the Marketing Authorisation holder	CER MEDICAL SRL
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	ossigeno 100%
D.3.2	Product code	[V03AN01]
D.3.4	Pharmaceutical form
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.3.9.2	Current sponsor code	-
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	ossigeno

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

adult critically ill patients requiring non-invasive (NIMV) or invasive mechanical ventilation (IMV)

Pazienti critici adulti che necessitano di ventilazione meccanica non invasiva (NIMV) o invasiva (IMV)

E.1.1.1

Medical condition in easily understood language

adult critically ill patients requiring non-invasive (NIMV) or invasive mechanical ventilation (IMV)

Pazienti critici adulti che necessitano di ventilazione meccanica non invasiva (NIMV) o invasiva (IMV)

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10040047
E.1.2	Term	Sepsis
E.1.2	System Organ Class	10021881 - Infections and infestations

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 verify the hypothesis that strict maintenance of normoxia improves survival in a wide population of mechanically ventilated critically ill patients compared to the application of conventional more liberal strategies of oxygen administration. Survival will be measured at ICU discharge.

L’obiettivo primario di questo studio è verificare l’ipotesi secondo la quale un rigoroso mantenimento di uno stato di normossia migliora la sopravvivenza in un’ampia popolazione di pazienti critici meccanicamente ventilati, se confrontata all’applicazione di strategie più liberali di somministrazione di ossigeno. La sopravvivenza sarà valutata alla dimissione dalla Terapia Intensiva.

E.2.2

Secondary objectives of the trial

To verify the hypothesis that, in a wide population of mechanically ventilated critically ill patients, the strict maintenance of normoxia compared to the application of conventional more liberal strategies of oxygen administration reduces the 90-day mortality, onset of new organ failures during ICU stay, occurrence of nosocomial infections during ICU stay (only microbiologically documented bloodstream, respiratory and surgical site infections will be considered), the length of mechanical ventilation, vasopressor use and ICU stay, the occurrence of ICU acquired weakness and cognitive dysfunction
The confirmation of the efficacy of a conservative strategy for oxygen administration in reduce the mortality rate among critically ill patients will lead to a profound revision of the current clinical practice and a rationale revision of the current recommendations would be mandatory, maybe also in other clinic

Gli obiettivi secondari si occupano di verificare l’ipotesi secondo cui il rigoroso mantenimento di uno stato di normossia, confrontato con l’applicazione di strategie convenzionali più liberali nella somministrazione di ossigeno, riduce la mortalità a 90 giorni, l’insorgenza di nuove insufficienze d’organo durante il ricovero in Terapia Intensiva, la durata della ventilazione meccanica, l’uso di farmaci vasoattivi, la permanenza in Terapia Intensiva e riduce anche l’insorgenza di debolezza Terapia Intensiva-realata e di disfunzione cognitiva.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: IMMUNE-O2 Sub-study vs 1 del 12-03-2018.
The objectives of the IMMUNE-O2 sub-study are to evaluate the relationship between different levels of arterial PO2 and the immune immune-system in critically ill patients and to verify the hypothesis that strict maintenance of normoxia compared to the application of conventional more liberal strategies of oxygen administration reduces the impairment of immune-system in critically ill patients.

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: IMMUNE-O2 Sub-study vs 1 del 12-03-2018.
Gli obiettivi del sottostudio IMMUNE-O2 sono di valutare la relazione tra i diversi livelli di PO2 arteriosa e il sistema immunitario immune nei pazienti critici e di verificare l'ipotesi che il mantenimento rigoroso della normossia rispetto all'applicazione di strategie convenzionali più liberali per somministrazione di ossigeno riduce la compromissione del sistema immunitario nei pazienti critici.

E.3

Principal inclusion criteria

- Critically ill patients admitted to participant ICUs,
- Age = 18 years without regards about sex and ethnicity;
- Expected length of ICU stay of more than 72 hours.
- Need of any respiratory support (IMV or NIMV) at admission and with an expected length of respiratory support = 6 hours
- Acquisition of informed consent.

- Pazienti in condizioni critiche ammesse alle ICU partecipanti,
- Età = 18 anni senza distinzione di sesso ed etnia;
- Durata prevista della permanenza in ICU di oltre 72 ore.
- Necessità di qualsiasi supporto respiratorio (IMV o NIMV) al momento del ricovero e con una durata prevista del supporto respiratorio = 6 ore
- Acquisizione del consenso informato

E.4

Principal exclusion criteria

- Pregnancy: Patients who are known to be pregnant or with a positive serum pregnancy test will be excluded. All potentially fertile females will be tested for pregnancy before enrolment in the study. We will consider as potentially fertile all female patients between 18 and 55 with no documented evidence of menopause, hysterectomy, surgical sterilization
- Admission to ICU after elective surgery
- ICU readmission (after a first discharge) in the study period;
- IMV or NIMV greater than 12 hours in the 28 days before study inclusion;
- Clinical decision to withhold life-sustaining treatment or “too sick to benefit” or patients with a life expectancy of less than 28 days due to a chronic or underlying medical condition.
- Previous enrolment in other interventional studies of targeted oxygen therapy;
- Acute respiratory failure on chronic obstructive pulmonary disease
- Acute respiratory distress syndrome (ARDS) with a PaO2/FiO2 ratio < 150.
- Long-term supplemental oxygen therapy.
- Patients candidate to hyperoxia treatment for reasons including (but not limited to) carbon monoxide poisoning or to hyperbaric oxygen therapy;

- Gravidanza:Saranno escluse le pazienti in gravidanza o con un test di gravidanza positivo. Tutte le donne potenzialmente fertili effettueranno un test di gravidanza prima dell'arruolamento nello studio. Considereremo fertili tutte le pazienti di sesso femminile tra i 18 ei 55 anni senza evidenza documentata di menopausa, isterectomia, sterilizzazione chirurgica;
- Ammissione alla terapia intensiva dopo chirurgia elettiva
- riammissione ICU (dopo una prima dimissione) nel periodo di studio;
- IMV o NIMV superiori a 12 ore nei 28 giorni precedenti l'inclusione nello studio;
- Decisione clinica di sospendere il trattamento di mantenimento della vita o "troppo malato per beneficiare" o di pazienti con un'aspettativa di vita inferiore a 28 giorni a causa di una condizione medica cronica o di base.
- Iscrizione precedente ad altri studi interventistici di ossigenoterapia mirata;
- Insufficienza respiratoria acuta nella broncopneumopatia cronica ostruttiva
- Sindrome da distress respiratorio acuto (ARDS) con un rapporto PaO2 / FiO2 <150.
- Ossigenoterapia supplementare a lungo termine.
- I pazienti candidati al trattamento con iperossia per ragioni che includono (ma non limitato a) avvelenamento da monossido di carbonio o ossigenoterapia iperbarica;

E.5 End points

E.5.1

Primary end point(s)

ICU mortality rate, defined as the number of deaths for any cause occurred during the ICU stay (censored at 90 days)

Tasso di mortalità in ICU, definito come il numero di decessi per qualsiasi causa verificatosi durante la permanenza in terapia intensiva (censurato a 90 giorni)

E.5.1.1

Timepoint(s) of evaluation of this end point

90 days

90 giorni

E.5.2

Secondary end point(s)

The occurrence of new organ dysfunction defined as a Sequential Organ Failure Assessment (SOFA) score =3 for the corresponding organ), occurring =48 hours after ICU admission; bloodstream, respiratory and surgical site infections (defined according to CDC definitions20). Only microbiologically documented bloodstream and respiratory tract infections were considered.; Ventilation-free hours (VFHs) during the ICU stay. VFHs is defined as the total number of hours of unassisted breathing between randomisation and ICU discharge. Periods of assisted breathing lasting less than 24 hours for surgical procedures will not count against the VFH calculation. Patients who are receiving extracorporeal membrane oxygenation (ECMO) will be defined as receiving assisted breathing irrespective of whether they are ventilated or not; Vasopressor free-hours (VasoFHs) during the ICU stay. VasoFHs is defined as the total number of hours without vasoactive drugs infusion used for hypotension between randomisation and ICU discharge.; Time to hospital discharge (censored at 90 days)

L'insorgenza di una nuova disfunzione d'organo definita come un punteggio di insufficienza d'organo sequenziale (SOFA) =3 per l'organo corrispondente), che si verifica =48 ore dopo l'ammissione all'ICU; infezioni del flusso sanguigno, respiratorie e del sito chirurgico (definite secondo le definizioni CDC20). Sono state prese in considerazione solo le infezioni del flusso sanguigno e delle vie respiratorie microbiologicamente documentate.; Le ore senza ventilazione (VFH) durante la permanenza in ICU . VFHs è definito come il numero totale di ore di respiro non assistito tra randomizzazione e dimissione in ICU. I periodi di respirazione assistita della durata inferiore a 24 ore per le procedure chirurgiche non verranno conteggiati rispetto al calcolo del VFH. I pazienti che ricevono ossigenazione della membrana extracorporea (ECMO) saranno definiti come soggetti a respirazione assistita indipendentemente dal fatto che siano ventilati o meno; Le ore libere di Vasopressore (VasoFH) durante la permanenza in terapia intensiva. VasoFHs è definito come il numero totale di ore senza infusione di farmaci vasoattivi utilizzati per ipotensione tra randomizzazione e dimissione dall'ICU.; Tempo di dimissione dall'ospedale (censurato a 90 giorni)

E.5.2.1

Timepoint(s) of evaluation of this end point

48 hours ; 90 days; during the ICU stay; during the ICU stay; 90 days

48 ore; 90 giorni; durante la permanenza in ICU; durante la permanenza in terapia intensiva; 90 giorni

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

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)

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

700

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-02-09.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects incapable of giving consent personally, please specify: the subjects enrolled in the study may be patients who are temporarily unconscious or for reasons related to their pathology or by pharmacological sedation. In this case, the local coor

potranno essere pazienti incoscienti temporaneamente o per ragioni legate alla loro patologia o per sedazione farmacologica. In questo caso, il coordinatore locale (sperimentatore) potrà decidere di arruolare comunque il paziente per il suo interesse

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

550

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1000

F.4.2.2

In the whole clinical trial

1000

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)

best supportive care

miglior terapia di supporto

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

2018-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-31

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