Trial of Hyperoxic O2 Therapy vs. Normoxic O2 Therapy in Sepsis

NCT ID: NCT02378545

Last Updated: 2017-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2016-11-10

Brief Summary

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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

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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

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Sepsis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hyperoxia

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.

Group Type ACTIVE_COMPARATOR

Oxygen

Intervention Type DRUG

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.

normoxia

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.

Group Type ACTIVE_COMPARATOR

Oxygen

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Medical Oxygen

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Plymouth NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tim Nutbeam, MBBS

Role: PRINCIPAL_INVESTIGATOR

University Hospital Plymouth NHS Trust

Locations

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Plymouth Hospitals NHS Trust

Plymouth, Devon, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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2015-000629-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15/P/020

Identifier Type: -

Identifier Source: org_study_id