An interventional study of Oxygen in Critical Illness and Respiratory Failure, sponsored by University College, London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-29.
Sponsored by University College, London · Not applicable, Interventional, and Other
The investigators propose to conduct a feasibility, multi-centre, randomised controlled trial of targeted oxygen therapy in adult critically ill patients receiving mechanical ventilation via an endotracheal tube as part of their treatment for respiratory failure. Participants will be allocated to either a normal blood oxygen target group or a lower than normal blood oxygen target group. The primary purpose of the study will be to assess the feasibility of recruiting complex patients who lack capacity into a clinical trial in which oxygenation is being assessed, and that the clinicians responsible for these patients are able to deliver the intervention effectively. The safety of using a lower than normal blood oxygen target will also be assessed and blood samples taken for subsequent investigation of the biological mechanisms underlying the observed changes.
Participants will be randomised (1:1) into either an intervention or control group. The intervention in this trial is tightly controlled administration of oxygen to patients to achieve a haemoglobin oxygen saturation (SpO2) of 88-92%. The control group will also have tightly controlled oxygen administration, but to achieve an SpO2 of 96% or above. The target for the control group represents a normal SpO2, whilst that in the intervention group is lower than what is considered to be normal. It should be noted that although lower than normal, this SpO2 is close to what the general public experience when travelling by pressurised aircraft as the fractional inspired oxygen concentration in that situation is only 0.15-0.17 (15-17%).
The controlled oxygen administration would commence as soon as possible after admission to the critical care unit and end following removal of the participant's artificial breathing tube. The researchers and clinical team cannot be blinded to treatment allocation, due to the nature of the intervention. Those analysing the data will be blinded to the intervention.
The investigators aim is to determine whether revising standard targets for blood oxygen levels in patients requiring artificial ventilation on a critical care unit is feasible and whether this affects specific blood biomarker levels.
Investigators in this area of expertise currently lack the information necessary to determine how much oxygen should be given to adult critically ill patients on a mechanical ventilator to assist their breathing in order to achieve the best clinical outcomes i.e. minimal morbidity and mortality. Excessive oxygen administration (both its concentration and duration) and hyperoxaemia (an excessively high blood oxygen level) are known to be harmful to critically ill patients. The reason for this is that oxygen in high concentration is toxic, because it results in the release of molecules called reactive oxygen species (ROS). ROS lead to a state known as 'oxidative stress', in which cells and tissues are rapidly destroyed by these destructive molecules.
The difficulty with treating critically ill patients is that they are usually extremely unwell, requiring artificial ventilation to support their breathing. Unfortunately, these patients appear to be exceptionally prone to the harms of oxidative stress, leading to permanent damage of their lungs. Yet it is precisely this group of patients who require high concentration oxygen to keep their blood oxygen levels within the normal. It has therefore been hypothesised that using lower blood oxygen targets than usual may be beneficial to these patients through the avoidance of excessively high concentrations of oxygen. The investigator proposes that in mechanically ventilated critically ill patients harm (morbidity and mortality) will be reduced by using 'targeted oxygen therapy' (TO2T) to achieve lower blood oxygen levels than normal when compared to standard practice (normal blood oxygen levels). The levels are only moderately lower than normal and well within what most clinicians would consider to be safe in these patients.
Prior to any large-scale study, it is important to understand if this approach to managing critically ill patients is feasible. This prospective, dual site randomised controlled trial will therefore establish whether it is possible to conduct a trial in which blood oxygen levels are carefully titrated by the critical care team, to achieve specific targets. Participants will be allocated into one of two groups: i) normal blood oxygen levels, and ii) low blood oxygen levels. For the time that participants are artificially ventilated by a breathing (endotracheal) tube, they will remain in their allocated treatment group. Information will be collected from the patient's charts and records during their stay on the CCU to assess the impact of the treatment. A series of blood samples will also be collected from participants to quantify the degree of oxidative stress through the measurement of several specific biomarkers. A total of 60 patients will be enrolled at two sites.
As oxygen is a drug that is administered to almost every patient admitted to a critical care unit (CCU), it is imperative that decisions regarding oxygenation are based upon evidence rather than conjecture. Limited work has been undertaken to date to understand whether lowering blood oxygen levels is achievable in this complex patient group. The information from this study will be used to design a subsequent much larger study to fully evaluate whether TO2T to achieve lower blood oxygen levels saves lives in critically ill patients. If lower blood oxygen levels improve survival in critically ill patients implementation of this intervention could have an immediate and cost-effective impact across the entire National Health Service.
1,780 studies on the registry are indexed under Critical Illness; 442 are open to participants now.
This study's enrollment of 34 is below the median of 90 across 926 interventional studies indexed under Critical Illness.
Browse Critical Illness studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Compared within Critical Illness, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
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Exclusion Criteria:
Patients participating in other interventional clinical trials
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The intervention is targeted oxygen therapy (TO2T) to achieve an arterial haemoglobin oxygen saturation (SpO2) of 88-92%.
Drug: Oxygen
The control group will have no specific SpO2 targets. Clinicians will be able to target SpO2 according to parameters they feel are suitable for the patient, according to standard UK practice.
Drug: Oxygen
targeted oxygen therapy
Feasibility to recruit
Ability to recruit
Time frame: 15 Months
Measurement of arterial blood gases
Measurement of arterial blood gases
Time frame: up to 21 days
Measurement of oxygen saturation
Measurement of oxygen saturation
Time frame: up to 21 days
Measurement of fraction of inspired oxygen
Measurement of fraction of inspired oxygen
Time frame: up to 21 days
Time to extubation / detachment from mechanical ventilation
Time to extubation / detachment from mechanical ventilation
Time frame: up to 21 days
Mechanical ventilation free days on ICU
Mechanical ventilation free days on ICU
Time frame: up to 21 days
Measurement of blood pressure
Measurement of blood pressure
Time frame: up to 21 days
Measurement of heart rate
Measurement of heart rate
Time frame: up to 21 days
Measurement of cardiac rhythm
Measurement of cardiac rhythm
Time frame: up to 21 days
Measurement of cardiac output and stroke volume (if measured)
Measurement of cardiac output and stroke volume (if measured)
Time frame: up to 21 days
Measurement of vasopressor doses
Measurement of vasopressor doses
Time frame: up to 21 days
Measurement of inotrope doses
Measurement of inotrope doses
Time frame: up to 21 days
Measurement of daily fluid balance
Measurement of daily fluid balance
Time frame: up to 21 days
Measurement of inotrope free days on ICU
Measurement of inotrope free days on ICU
Time frame: up to 21 days
Measurement of vasopressor free days on ICU
Measurement of vasopressor free days on ICU
Time frame: up to 21 days
Measurement of Urea
Measurement of Urea
Time frame: up to 21 days
Measurement of creatinine
Measurement of creatinine
Time frame: up to 21 days
Measurement of urine output
Measurement of urine output
Time frame: up to 21 days
The need for renal replacement therapy
The need for renal replacement therapy
Time frame: up to 21 days
Renal replacement therapy free days on ICU
Renal replacement therapy free days on ICU
Time frame: up to 21 days
Measurement of transaminases
Measurement of transaminases
Time frame: up to 21 days
Measurement of blood clotting values
Measurement of blood clotting values
Time frame: up to 21 days
Measurement of bilirubin
Measurement of bilirubin
Time frame: up to 21 days
Measurement of blood lactate
Measurement of blood lactate
Time frame: up to 21 days
Measurement of Troponin
Measurement of Troponin
Time frame: up to 21 days
Adverse events
Adverse events
Time frame: 90 days
SOFA score change
Sequential Organ Failure Assessment (SOFA) score change
Time frame: up to 21 days
APACHE II score change
Acute Physiology and Chronic Health Evaluation (APACHE) II score change
Time frame: up to 21 days
Length of ICU stay
Length of stay in intensive care unit
Time frame: up to 21 days
Length of hospital stay
Length of hospital stay
Time frame: 90 days
Mortality rates
Days alive
Time frame: 90 days
Days alive out of Hospital
Days alive out of Hospital
Time frame: 90 days
Plan to share: No
Ran from Jan 2018 to primary completion in Nov 2019, 22 months.
Of 400 non-industry interventional studies with no phase under Critical Illness, half reached primary completion within 21 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 40. This study's 22 months is close to that.
Counting every sponsor, half of 404 studies reached it within 21 months; a quarter within 12 and three quarters within 40.
Critical Illness covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
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This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Oxygen