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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

9 Dec 2024 → ongoing

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ESICM

External identifiers

EU CT number

2024-518092-62-00

EudraCT number

2018-002525-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

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.

Secondary objectives 1

1. 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 (respiratory, cardiovascular, renal and hepatic after 48 hours from ICU admission) 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 clinical scenarios such as emergency departments.

Conditions and MedDRA coding

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - 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.

Exclusion criteria 1

1. - 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;

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 1

1. - 90-day mortality, - The occurrence of new organ dysfunction defined as a SOFA score ≥3 for the corresponding organ, occurring ≥48 hours after ICU admission, - bloodstream, respiratory and surgical site infections, - VFHs during the ICU stay, - VasoFHs during the ICU stay, - ICU free days at 28-day and at 90-day, - Cognitive Dysfunction at ICU discharge (censored at 90 days) by MMSE, - ICU acquired weakness at ICU discharge (censored at 90 days) by MRC Scale.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Massimo Girardis

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Massimo Girardis

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications