Condition category
Surgery
Date applied
20/05/2008
Date assigned
10/07/2008
Last edited
08/03/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Some children are born with a heart defect that causes the levels of oxygen in the blood to be lower than expected for a healthy child. We call children with this condition ‘cyanotic children’. Often, the only way of improving the levels of oxygen in the child’s blood is by operating on the heart.
When children undergo heart surgery, the job of pumping blood around the body is taken over by a heart-lung bypass machine. This machine also provides the blood with oxygen and allows surgical staff to decide how much oxygen the child gets during surgery.
Currently we give cyanotic children 100% oxygen from the beginning of surgery (when they are attached to the heart-lung bypass machine) and then throughout their surgery. This is widely accepted standard practice. However, after the operation cyanotic children sometimes suffer damage to the cells of their heart and other organs. This is thought to be caused by introducing 100% oxygen at the beginning of surgery when the child’s body is not used to it.
Some evidence suggests it may be better to give lower levels of oxygen at the start of the operation, similar to the level the child is used to, and then slowly bring up the level of oxygen by the end of the operation. The level the oxygen given at the end of the operation depends on the child’s specific condition.
The Oxic2 study aims to find out which is the best method of giving oxygen to a cyanotic child during surgery by seeing if it leads to any differences in how the child recovers from the operation.

Who can participate?
Cyanotic children undergoing heart surgery.

What does the study involve?
To join the study parents or guardians are required to sign a consent form. After this, and as close as possible to the time of surgery, children will be randomly allocated to one of two groups:
1. Children in the first group will get the higher level of oxygen (100%) at the start of surgery and throughout their operation;
2. Children in the second group will be given the level of oxygen they are used to at the start of surgery and then slowly given more until they reach a level we would expect to see by the end of the operation.
Everything else about the operation and after care is the same, regardless of which group a child is in.
With permission, any waste heart tissue removed during the operation will be kept for examination to see if the different oxygen levels affect the way heart muscle tissue makes protein and other chemicals. The samples will be stored for the duration of the study and destroyed at the end.
After the operation, information will be collected about the type and amount of care and medical support each child needs while recovering in hospital. This information will be used to compare how fast children recover in each group.
Parents/guardians will also be contacted at 3 months and 12 months after the operation to ask if their child has been admitted to hospital for any reason.
Children aged 2½ years or younger will be assessed for their current stage of development using the Bayley Infant Development Scale to see whether the way their oxygen was managed during the operation has any effect on their development after the operation. The assessments take place at the child’s home (or an alternative place to suit) and will be performed before the operation, at 3 months after the operation and again at 12 months after the operation. Children who are less than a month old at the time of their operation will not have an assessment before the operation, but may still have the assessments at 3 and 12 months.The test involves a play session lasting between an hour and 90 minutes depending on the age of the child. Objects and toys are used to see how a child makes sense of the world, how they communicate, and to assess their physical development. The assessment also includes some questions for the parents/guardians to answer about their child’s behaviour.
When a child reaches school age, we may ask permission to access their school entry results, which along with the Bayley assessments will provide information about the long term effects of the two oxygen levels.

What are the possible benefits and risks of participating?
Giving high levels of oxygen during a heart operation is standard practice at our hospital so if a child is in the group where the high level of oxygen is used from the beginning of surgery then the risks and benefits are the same as if they were not participating in the study.
The risks and benefits for the lower level of oxygen have not been directly compared with the higher levels of oxygen before. We are doing the study in order to be able to make this comparison. However, we do not believe there is any extra risk as a result of taking part in this study.
One possible benefit is that some parents/guardians find it reassuring for their child to have the Bayley assessments as this is an extra assessment to what the child would normally receive. However, parents/guardians may feel they are unable to give the time required for the assessments.

Where is the study run from?
The study is run by the University of Bristol from the Bristol Royal Hospital for Children at the University Hospitals Bristol NHS Trust (UK).

When is study starting and how long is it expected to run for?
The study started in 2008 and is expected to run until approximately September 2014.

Who is funding the study?
The research is funded by two medical research charities, The BUPA Foundation and the Garfield Weston Trust (UK).

Who is the main contact?
Research Nurse: Karen Sheehan
Trial Coordinator: Lucy Dreyer / Lucy Ellis
Chief Investigator: Prof. Massimo Caputo
oxic2-trial@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Massimo Caputo

ORCID ID

Contact details

Level 7
Bristol Royal Infirmary
Marlborough Street
Bristol
BS2 8HW
United Kingdom

Additional identifiers

EudraCT number

2010-019713-21

ClinicalTrials.gov number

Protocol/serial number

CS/2007/2678

Study information

Scientific title

Acronym

OXIC-2

Study hypothesis

The principal hypothesis is that using lower levels of oxygen during cardiopulmonary bypass will reduce the levels of re-oxygenation injury to paediatric patients, measured both in terms of clinical outcomes (e.g., length of post-operative hospital stay and type of care required) and in long term behavioural outcomes (measured preoperatively and 3 and 12 months post-operatively using the Bayley III Infant Development Scales).

As of 26/07/2012 the anticipated end date of this trial was updated from 01/06/2012 to 01/09/2014

Ethics approval

North Somerset and South Bristol Research Ethics Committee. Date of approval: 19/12/2007 (ref: 07/HO106/153)

Study design

Single-centre open randomised controlled trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Children with a congenital heart defect which results in cyanosis and which are amenable to surgical repair

Intervention

All children will undergo surgery for repair of congenital cyanotic heart disease. All operations will be performed using cardiopulmonary bypass (CPB) with ascending aortic cannulation and bicaval venous cannulation. The experimental group will have normoxic (70-100 mmHg) CPB and the control group will have standard (relatively hyperoxic) (150-200 mmHg) CPB. Equal numbers of participants will be allocated to the two arms of the trial, stratified by age.

Intervention type

Procedure/Surgery

Phase

Not Applicable

Drug names

Primary outcome measures

Clinical outcomes:
1. Duration of inotropic support
2. Intubation time
3. Length of intensive care unit (ICU) stay
4. Length of hospital stay

Secondary outcome measures

1. In-hospital mortality and morbidity (e.g., blood loss, transfusion requirement, abnormal echocardiographic findings, abnormal post-operative blood test results)
2. Developmental assessments using the Bayley III Infant Development Scales measured pre-operatively and at 3 and 12 months after surgery (children aged up to 42 months only)
3. Assessment of brain injury using a biochemical marker (astroglial S100) measured pre-operatively, 10 and 30 minutes after starting CPB, 10 minutes after the end of surgery, and 4 and 24 hours after surgery
4. Renal function, measured by plasma creatinine and urea nitrogen levels taken every 24 hours for the first 5 days after surgery
6. Gene expression profiles associated with rexoygenation injury to the heart muscle

Overall trial start date

01/06/2008

Overall trial end date

01/09/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 08/03/2013:
1. Cyanotic children undergoing operations to repair or palliate a heart defect
2. Children must be ≥1 month old to be eligible for all the neurocognitive assessments. Children <1 month old are eligible only for the 3 and 12 month post-operative neurocognitive assessments

Previous inclusion criteria until 08/03/2013:
1. Cyanotic children undergoing operations to repair or palliate a heart defect
2. Children aged >= 1 month of age

Previous inclusion criteria until 26/07/2012:
1. Cyanotic children (both males and females) undergoing operations to repair a heart defect
2. Children aged >= 1 month of age

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

90

Participant exclusion criteria

Current exclusion criteria as of 08/03/2013:
1. Children with a preoperative diagnosis of Down’s syndrome or other developmental disorders are excluded from the neurocognitive assessments as part of the trial, but may be included in the main study
2. Emergency operations
3. Children requiring cardiovascular and/or respiratory support prior to study entry

Previous exclusion criteria until 08/03/2013:
1. Children with a preoperative diagnosis of Down's syndrome or other developmental disorders are excluded from the neurocognitive assessments as part of the trial, but may be included in the main study
2. Emergency operations
3. Patients undergoing arterial switch procedure
4. Neonatal patients (<1 month old)

Previous exclusion criteria as of 26/07/2012:
1. Preoperative diagnosis of Down's syndrome or other developmental disorders

Recruitment start date

01/06/2008

Recruitment end date

01/09/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Level 7
Bristol
BS2 8HW
United Kingdom

Sponsor information

Organisation

University Hospitals Bristol NHS Foundation Trust

Sponsor details

Level 3 Education Centre
Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom
+44 (0)117 342 0233
research@uhbristol.nhs.uk

Sponsor type

Government

Website

http://www.uhbristol.nhs.uk/research-innovation/

Funders

Funder type

Charity

Funder name

Bupa Foundation (UK) (ref: 5 FEB06)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

Garfield Weston (UK) (ref: PMS/MMS, 07/08, 3014)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19577081

Publication citations

  1. Results

    Caputo M, Mokhtari A, Rogers CA, Panayiotou N, Chen Q, Ghorbel MT, Angelini GD, Parry AJ, The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative stress and inflammatory response in cyanotic pediatric patients undergoing open cardiac surgery: a randomized controlled trial., J. Thorac. Cardiovasc. Surg., 2009, 138, 1, 206-214, doi: 10.1016/j.jtcvs.2008.12.028.

Additional files

Editorial Notes