SepsisPhase 4HO2T or NO2TNCT02378545
Trial of Hyperoxic O2 Therapy vs. Normoxic O2 Therapy in Sepsis
A Phase 4 study testing Oxygen in people with Sepsis, run by University Hospital Plymouth NHS Trust at 1 site in United Kingdom.
Trial summary
The motivation for this study comes from a desire to improve the mortality of patients with sepsis. Oxygen is cheap, readily available and is included in current United Kingdom Emergency Department guidelines, but it may also be harmful to patients with sepsis - it is important to know if this is the case. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2015to 10 Nov 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients aged 18 years or above.
- Diagnosed with presumed 'Sepsis'.
- Arrive at Derriford Emergency Department by ambulance.
- Provision of informed consent.
- Willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the study.
Who cannot join
- Female participants who are pregnant
- Existing diagnosis of chronic obstructive pulmonary disease (COPD)
- A primary diagnosis (or suspected diagnosis) of:
- an acute cerebral vascular event
- acute coronary syndrome
- acute pulmonary oedema
Show all 14Show fewer
- status asthmatic
- major cardiac arrhythmia (as part of primary diagnosis)
- seizure
- drug overdose
- injury from burn or trauma
- Participants who require immediate intubation and ventilation on arrival in the Emergency Department
- Participants undergoing or have undergone cardiopulmonary resuscitation in the pre-hospital phase of their treatment.
- Current participation in another Clinical Trial of an Investigational Medicinal Product (CTIMP).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Plymouth Hospitals NHS Trust
Plymouth, Devon, PL6 8BX
About this study
Official title: (Feasibility) Open Label Randomised Controlled Trial of Hyperoxic O2 Therapy vs. Normoxic O2 Therapy in Sepsis
The motivation for this study comes from a desire to improve the mortality of patients with sepsis. Oxygen is cheap, readily available and is included in current United Kingdom Emergency Department guidelines, but it may also be harmful to patients with sepsis - it is important to know if this is the case.
This study is a pilot study to also assess the feasibility of delivering a larger adequately powered study.
Read the detailed description
Currently there is no consensus on the use of oxygen therapy in sepsis resuscitation. Uncertainty exists as to whether increasing oxygen above physiological levels (hyperoxia) or maintaining physiological oxygen concentration (normoxia) confers the most benefit to patients. By indicating whether hyperoxia is beneficial or not, the study hopes to further increase the effectiveness of sepsis resuscitation.
In patients with sepsis there are convincing, coherent pathophysiological and evidence-based justifications which support both normoxia and hyperoxia.
Why normoxia may benefit patients with sepsis: Enhanced oxidative and nitrosative stress resulting from increased formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs during sepsis and is assumed to have major importance during the development of shock-related hypotension, impairment of microcirculatory perfusion, mitochondrial dysfunction, and tissue injury. It is well established that increasing the inhaled fraction of inspired oxygen (FiO2) leads to an increase in ROS production. The negative effects of hyperoxia in humans have been well demonstrated in a number of pathological conditions including stroke, myocardial infarction and some lung diseases. The pathological processes behind each of these conditions is very different from that of sepsis.
In a small observational study (88 patients) in patients with sepsis, of the hyperoxic patients, 8% died in hospital versus 6% with normoxia. Further prospective controlled trials are required. The deleterious effects of hyperoxia have also been demonstrated in a rat model.
Why hyperoxia may benefit patients with sepsis: Underlying cellular hypoxia, which may be difficult to detect, has been suggested as a major cause of morbidity and mortality in sepsis - this may be reversed or attenuated by high flow oxygen.
Hyperoxia may reverse arterial hypotension and exert anti-inflammatory and antiapoptotic properties. The beneficial effects of hyperoxia have been demonstrated in rat and pig models through increased survival and reduced inflammation.
One study in rats showed the most benefit on survival from oxygen administration when oxygen was administered in the first 4 hours of the trial, with no additional benefit beyond this time.
A further study (also in rats) demonstrated that 6 hours of oxygen per 24 hours for the first 48 hours following introduction of sepsis had the most beneficial anti-inflammatory effects.
- Conditions
- Sepsis
- Being tested
- Oxygen
- Keywords
- Sepsis, Hyperoxia, Sepsis Six, Oxygen delivery
- Medical subject headings
- Sepsis, Hyperoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxygenDrug
Also called Medical Oxygen
On the Hyperoxia arm: Oxygen will be administered using a non-re-breathe oxygen mask applied over the face and nose.
On the Normoxia arm: In many cases oxygen will not be administered. If required the minimum percentage required to reach the target saturations will be administered. In a majority of cases this will be via a venturi mask.
| Study group | Role | What they receive |
|---|---|---|
| Hyperoxia | Active comparator | Oxygen will be administered using a non-re-breathe oxygen mask applied over the face and nose. The oxygen delivery device will be set to deliver oxygen at 15 litres per minute. The oxygen will be continuously delivered throughout the patients stay in the Emergency Department. Receives: Drug: Oxygen |
| normoxia | Active comparator | Oxygen will not be administered if a patient's oxygen saturations (as measured using a pulse oximeter) are less than 94%. If a patient's oxygen saturations are less than 94%, oxygen will be 'titrated' using a 'venturi' type oxygen delivery device to achieve target saturations of 94%. Following initial dynamic titration (to identify correct oxygen delivery level) the oxygen delivery device will be re-evaluated hourly during the patient's stay in the emergency department. Receives: Drug: Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does delivery of high flow oxygen (hyperoxic oxygen therapy) compared to titrated oxygen therapy (normoxic oxygen therapy) reduce mortality at 90 days
Adult patients with sepsis presenting to the emergency department by ambulance.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startOct 2015
- Primary completionOct 2016
- Study completion10 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Plymouth NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Nutbeam, MBBS, Principal investigator, University Hospital Plymouth NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02378545
- Sponsor's protocol ID
- 15/P/020
- Other IDs
- 2015-000629-35, 2015
- Acronym
- HO2T or NO2T
- Status last verified
- Oct 2016
- First submitted
- 12 Feb 2015
- Last updated
- 19 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (Feasibility) Open Label Randomised Controlled Trial of Hyperoxic O2 Therapy vs. Normoxic O2 Therapy in Sepsis
- ClinicalTrials.gov ID
- NCT02378545
- Acronym / sponsor ID
- HO2T or NO2T / 15/P/020
- Conditions
- Sepsis
- Keywords
- Sepsis, Hyperoxia, Sepsis Six, Oxygen delivery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital Plymouth NHS TrustUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- 10 Nov 2016 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The motivation for this study comes from a desire to improve the mortality of patients with sepsis. Oxygen is cheap, readily available and is included in current United Kingdom Emergency Department guidelines, but it may also be harmful to patients with sepsis - it is important to know if this is the case.
This study is a pilot study to also assess the feasibility of delivering a larger adequately powered study.
Detailed description
Currently there is no consensus on the use of oxygen therapy in sepsis resuscitation. Uncertainty exists as to whether increasing oxygen above physiological levels (hyperoxia) or maintaining physiological oxygen concentration (normoxia) confers the most benefit to patients. By indicating whether hyperoxia is beneficial or not, the study hopes to further increase the effectiveness of sepsis resuscitation.
In patients with sepsis there are convincing, coherent pathophysiological and evidence-based justifications which support both normoxia and hyperoxia.
Why normoxia may benefit patients with sepsis: Enhanced oxidative and nitrosative stress resulting from increased formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs during sepsis and is assumed to have major importance during the development of shock-related hypotension, impairment of microcirculatory perfusion, mitochondrial dysfunction, and tissue injury. It is well established that increasing the inhaled fraction of inspired oxygen (FiO2) leads to an increase in ROS production. The negative effects of hyperoxia in humans have been well demonstrated in a number of pathological conditions including stroke, myocardial infarction and some lung diseases. The pathological processes behind each of these conditions is very different from that of sepsis.
In a small observational study (88 patients) in patients with sepsis, of the hyperoxic patients, 8% died in hospital versus 6% with normoxia. Further prospective controlled trials are required. The deleterious effects of hyperoxia have also been demonstrated in a rat model.
Why hyperoxia may benefit patients with sepsis: Underlying cellular hypoxia, which may be difficult to detect, has been suggested as a major cause of morbidity and mortality in sepsis - this may be reversed or attenuated by high flow oxygen.
Hyperoxia may reverse arterial hypotension and exert anti-inflammatory and antiapoptotic properties. The beneficial effects of hyperoxia have been demonstrated in rat and pig models through increased survival and reduced inflammation.
One study in rats showed the most benefit on survival from oxygen administration when oxygen was administered in the first 4 hours of the trial, with no additional benefit beyond this time.
A further study (also in rats) demonstrated that 6 hours of oxygen per 24 hours for the first 48 hours following introduction of sepsis had the most beneficial anti-inflammatory effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyperoxia | Active comparator | Drug: OxygenOxygen will be administered using a non-re-breathe oxygen mask applied over the face and nose. The oxygen delivery device will be set to deliver oxygen at 15 litres per minute. The oxygen will be continuously delivered throughout the patients stay in the Emergency Department. |
| normoxia | Active comparator | Drug: OxygenOxygen will not be administered if a patient's oxygen saturations (as measured using a pulse oximeter) are less than 94%. If a patient's oxygen saturations are less than 94%, oxygen will be 'titrated' using a 'venturi' type oxygen delivery device to achieve target saturations of 94%. Following initial dynamic titration (to identify correct oxygen delivery level) the oxygen delivery device will be re-evaluated hourly during the patient's stay in the emergency department. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients aged 18 years or above.
- Diagnosed with presumed 'Sepsis'.
- Arrive at Derriford Emergency Department by ambulance.
- Provision of informed consent.
- Willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the study.
Key exclusion criteria (14 listed)
- Female participants who are pregnant
- Existing diagnosis of chronic obstructive pulmonary disease (COPD)
- A primary diagnosis (or suspected diagnosis) of:
- Participants who require immediate intubation and ventilation on arrival in the Emergency Department
- Participants undergoing or have undergone cardiopulmonary resuscitation in the pre-hospital phase of their treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxygenAlso: Medical OxygenOn the Hyperoxia arm: Oxygen will be administered using a non-re-breathe oxygen mask applied over the face and nose. On the Normoxia arm: In many cases oxygen will not be administered. If required the minimum percentage required to reach the target saturations will be administered. In a majority of cases this will be via a venturi mask. | Drug | Hyperoxia, normoxia |
Primary outcome
Does delivery of high flow oxygen (hyperoxic oxygen therapy) compared to titrated oxygen therapy (normoxic oxygen therapy) reduce mortality at 90 days
Time frame: 90 days
Adult patients with sepsis presenting to the emergency department by ambulance.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Nutbeam, MBBS principal investigator
University Hospital Plymouth NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oxygen in people with Sepsis, run by University Hospital Plymouth NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does delivery of high flow oxygen (hyperoxic oxygen therapy) compared to titrated oxygen therapy (normoxic oxygen therapy) reduce mortality at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2017; AzTrials last refreshed its copy on 7 Nov 2026.