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Trial registered on ANZCTR


Registration number
ACTRN12617000306314
Ethics application status
Approved
Date submitted
29/12/2016
Date registered
27/02/2017
Date last updated
27/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Oxygen concentrations and responses of the immune system in surgery
Scientific title
Does variation of inspired oxygen concentration at the time of
reperfusion of the lower limb during elective knee surgery alter oxidative stress and immune activation
Secondary ID [1] 290810 0
Nil Known
Universal Trial Number (UTN)
U1111-1191-2111
Trial acronym
ORIS-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Surgery 301465 0
Reperfusion 301466 0
Condition category
Condition code
Anaesthesiology 301184 301184 0 0
Anaesthetics
Surgery 301823 301823 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Alteration of inspired oxygen concentration prior to release of tourniquet. These patients are undergoing general anaesthesia and routinely receive oxygen administration at a concentration of 0.3 following anaesthesia induction up to 30 minutes prior to release of the lower limb tourniquet . The inspired oxygen concentration will be changed to either FiO2 = 0.3, 0.5 or 0.8 30 minutes prior to release of the tourniquet and this concentration will be continued until the end of surgery.
Intervention code [1] 296734 0
Treatment: Drugs
Comparator / control treatment
Control group comprised FiO2 of 0.3
Control group
Active

Outcomes
Primary outcome [1] 300607 0
Plasma concentrations Isofurans
Timepoint [1] 300607 0
T1 Baseline sample, prior to anaesthesia induction
T2 Immediately prior to a change in oxygen concentration, 30 minutes prior to deflation of the tourniquet
T3 5 minutes after T2
T4 10 minutes after T2
T5 20 minutes after T2
T6 Immediately prior to deflation of the tourniquet
T7 5 minutes following deflation of the tourniquet
T8 120 minutes following deflation of the tourniquet
Secondary outcome [1] 330402 0
Concentrations of lymphocyte subpopulations on whole blood;

The subpopulations are :

B cells, T cells, CD4 , CD8 cells, Natural killer cells and naieve b cells
Timepoint [1] 330402 0
35 minutes following tourniquet release

Eligibility
Key inclusion criteria
Adult patients undergoing Knee Replacement surgery requiring the use of a tourniquet for more than 60 minutes
ASA 1 - 3
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systemic infection Immunosuppressive medication
Extensive tissue trauma Multiple tourniquet episodes
Concurrent NSAID use Chronic opioid abuse, IVDU
Recent MI (< 4 weeks) CRF (creatinine > 125 micromol/l)
Liver failure Obstructive Sleep Apnoea, BMI > 40
Likely intraop O2 requirement > 50 %
or supplemental O2 preoperatively

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Opaue sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer Sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Mixed models will be employed to analyse changes over time

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
3/02/2012
Date of last participant enrolment
Anticipated
Actual
22/10/2014
Date of last data collection
Anticipated
Actual
22/10/2014
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
WA
Recruitment postcode(s) [1] 14940 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 295239 0
Hospital
Name [1] 295239 0
Royal Perth Hospital
Country [1] 295239 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Wellington Street
Perth
WA, 6000
Country
Australia
Secondary sponsor category [1] 294066 0
None
Name [1] 294066 0
None
Address [1] 294066 0
Country [1] 294066 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296578 0
Royal perth Hospital HREC
Ethics committee address [1] 296578 0
Royal Petrh Hospital
Wellington Street
Perth
WA, 6000
Ethics committee country [1] 296578 0
Australia
Date submitted for ethics approval [1] 296578 0
08/12/2008
Approval date [1] 296578 0
10/10/2011
Ethics approval number [1] 296578 0
EC 2008/211

Summary
Brief summary
Surgery for many procedures involving the leg requires the surgeons to stop the blood flow for a variable period of time. During this period certain changes occur in the leg. When the blood supply is restored, these changes result in a very strong stimulus to the immune system. Some of these changes are beneficial, promoting healing of wounds and repair of damaged tissues. Some of these changes, however, can cause depression of the immune system and make infections more likely. During surgery, the anaesthetist administers anaesthetic drugs, and oxygen. The amount of oxygen that is given varies according to a number of factors. There is some evidence that the amount of oxygen in the body at the time of restoring blood supply to a limb may be of importance. This importance is in terms of the damage that may occur during surgery and the recovery from the surgery. We do not know how much oxygen is good or bad when the blood supply is restored, and we would like to perform a study looking at this question.
At all times in this study, patients will receive at least more than the minimum amount of oxygen that is necessary for all of the bodies organs to function entirely normally, and make a complete recovery from anaesthesia and surgery.

Study protocol
After randomisation to one of the three groups, patients will receive a standardised general anaesthetic based upon the gas “Sevoflurane”. All patients will receive 30% oxygen during the surgery, up until the time of restoring blood supply to the leg. At that point patients in one of three groups will receive either
a). 30% oxygen before the blood supply is restored and continued until the end of surgery
-(Conventional Care)
b). 30% oxygen before the blood supply is restored and then 50 % until the end of surgery
c). 30% oxygen before the blood supply is restored and then 80 % until the end of surgery
- all of the above are in addition to the usual standard anaesthetic care.

A small ( 3 ml. ) sample of blood will be taken at ten separate times up until 2 hours after the blood supply is restored. The study period then ends for each patient at that point.

In summary, our hypothesis is that different concentrations of oxygen will produce changes in biochemistry that we wish to measure. These changes will help us to identify which is the best oxygen concentration to give to patients who are having this type of surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71354 0
Prof Tomas Corcoran
Address 71354 0
Department of Anaesthesia and Pain Medicine
Royal Perth Hospital
Wellington Street
Perth
WA, 6000
Country 71354 0
Australia
Phone 71354 0
+61414791151
Fax 71354 0
Email 71354 0
[email protected]
Contact person for public queries
Name 71355 0
Prof Tomas Corcoran
Address 71355 0
Department of Anaesthesia and Pain Medicine
Royal Perth Hospital
Wellington Street
Perth, WA, 6000
Country 71355 0
Australia
Phone 71355 0
+61414791151
Fax 71355 0
Email 71355 0
[email protected]
Contact person for scientific queries
Name 71356 0
Prof Tomas Corcoran
Address 71356 0
Department of Anaesthesia and Pain Medicine
Royal Perth Hospital
Wellington Street
Perth, WA, 6000
Country 71356 0
Australia
Phone 71356 0
+61414791151
Fax 71356 0
Email 71356 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseIncreased inspired oxygen concentration does not adversely affect oxidative stress and the resolution of inflammation during reperfusion in patients undergoing knee replacement surgery.2021https://dx.doi.org/10.1080/10715762.2020.1868451
N.B. These documents automatically identified may not have been verified by the study sponsor.