Conservative Versus Conventional Oxygen Administration in Critically Ill Patients

NCT04198077 | Unknown Phase 4 DMC

• 2 other identifiers: ICUconservativeO22018-002525-35
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Oxygen supplementation in the inspired mixture is commonly used in critically ill patients and observational studies highlight that those patients remain hyperoxemic for substantial periods during Intensive Care Unit stay. However, exposure to inhaled oxygen-enriched mixtures is widely recognized as potentially harmful and cause of organ damage. Although, the specific level of arterial oxygen partial pressure (PaO2) considered harmful, or the dangerous duration of hyperoxia, is not determined yet as there are no clinical trials on humans that evaluate the appropriate percentage of oxygen considered safe to maintain an adequate tissue oxygen availability. The study is designed as a multicentre, open-label, two parallel groups, randomized superiority clinical trial. The study will involve 10 European intensive care units and will recruit adult critically ill patients requiring mechanical ventilation with an expected length of stay of more than 72 hours admitted to the Intensive Care Unit. Within the conventional group, participants will receive an inspired oxygen fraction (FiO2) aiming to maintain an oxygen saturation by pulse oximetry (SpO2) equal or major than 98 percentage, accepting an upper limit of PaO2 of 150 mmHg and a lower limit of 60 mmHg. Patients in the conservative group will receive the lowest FiO2 to maintain SpO2 between 94 and 98 percentage, or when available a PaO2 between 60 mmHg and 100 mmHg. The primary objective of this study is 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 Intensive Care Unit discharge. The confirmation of the efficacy of a conservative strategy for oxygen administration in reducing 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

Critical Illness; Respiration, Artificial; Hyperoxia; Hyperoxemia

Keywords

Mechanical Ventilation; Critically ill patient; Oxygenation; ICU; Intensive Care Unit

Outcome Measures

Primary Outcomes (1)

• Mortality

  Intensive Care Unit mortality rate, defined as the number of deaths for any cause

  Intensive Care Unit discharge censored at day 90

Secondary Outcomes (9)

• 90-day mortality

  At day 90 from admission

• Occurrence of new organ dysfunction

  From ≥48 hours after ICU admission to ICU discharge, censored at day 90

• Infections

  From ≥48 hours after ICU admission to ICU discharge, censored at day 90

• Ventilation-free hours (VFHs)

  From randomisation to ICU discharge, censored at day 90

• Vasopressor free-hours

  From randomisation to ICU discharge, censored at day 90

Study Arms (2)

CONSERVATIVE

EXPERIMENTAL

Participants in the conservative group will receive the lowest FiO2 to maintain SpO2 between 94 and 98 percentage, or when available a PaO2 between 70 mmHg and 100 mmHg. A SpO2 alarm limit of 99 percent will apply whenever supplemental oxygen is being administered. The FiO2 will be reduced or oxygen supplementation discontinued whenever the SpO2 or PaO2 exceeded 98 percent or 100 mm Hg. An oxygen supplementation will be given only if SpO2 falls below 94 percent. Pre-oxygenation with FiO2 1.0 will not be performed during in-hospital transports or in anticipation of diagnostic and therapeutic manoeuvres.

Drug: Oxygen

CONVENTIONAL

ACTIVE COMPARATOR

In the conventional group, participants will receive a FiO2 aiming to maintain a SpO2 equal or major than 98 percentage, accepting an upper limit of PaO2 of 150 mmHg and a lower limit of 70 mmHg. The use of a FiO2 of less than 0.3 whilst ventilated is discouraged. According to standard Intensive Care Unit practice, control patients will receive a FiO2 of 1.0 during endotracheal intubation manoeuvre, airway suction or in-hospital transfers.

Drug: Oxygen

Interventions

Oxygen DRUG

Administered via invasive or non-invasive mechanical ventilation with fraction of inspired oxygen between 0.21 and 1.0

CONSERVATIVE; CONVENTIONAL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Critically ill patients admitted to participant Intensive Care Units
• Age major than 18 years without regards about sex and ethnicity
• Expected length of Intensive Care Unit stay of more than 72 hours
• Need of any respiratory support (invasive or non invasive mechanical ventilation) at admission and with an expected length of respiratory support major than 6 hours
• Acquisition of informed consent

You may not qualify if:

• Pregnancy
• Admission to Intensive Care Unit after elective surgery
• Intensive Care Unit readmission (after a first discharge) in the study period
• 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 with a PaO2/FiO2 ratio less than 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

Sponsors & Collaborators

• University of Modena and Reggio Emilia: lead

Study Sites (1)

Girardis Massimo

Modena, 41124, Italy

RECRUITING

Related Publications (27)

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MeSH Terms

Conditions

Critical Illness; Respiratory Aspiration; Hyperoxia

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Central Study Contacts

Massimo Girardis

CONTACT

0594224934; girardis.massimo@unimore.it

Emanuela Biagioni

CONTACT

0594224934; emanuela.biagioni@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The study is conceived as single blinded: only the patients will be not aware of the group allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Anesthesiology and Intensive Care Unit, University Hospital of Modena

Model Details: The study is designed as multicentre, open label, two parallel groups, randomized superiority clinical trial. The included patients will be randomized in 1:1 ratio in conservative and conventional group. A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by center. Central randomisation will be performed using a secure, web-based, randomisation interface. The allocation sequence will be generated by the study statistician using computer generated random numbers.

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 13, 2019
• Study Start: December 4, 2019
• Primary Completion: December 4, 2022
• Study Completion: March 4, 2023
• Last Updated: May 4, 2021

Record last verified: 2021-05

Locations

IT (1)