Condition category
Surgery
Date applied
13/01/2009
Date assigned
27/02/2009
Last edited
21/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
During on-pump cardiac surgery it is important to ensure that a patient's organs are receiving the correct amount of oxygen. At present, counting a patient's red blood cells (the 'haematocrit' level) is the standard method of measuring the oxygen level. When the haematocrit drops below a certain level (threshold) a transfusion is given. This threshold is the same in all patients. This may not be the best method because the oxygen supply to an individual organ can be low (which can cause injury) while the overall haematocrit level remains within the normal range. On the other hand, transfusing blood unnecessarily may cause the body more stress and reduce its ability to fight infection.
In this study a patient-specific method for deciding when to transfuse, based on the amount of oxygen reaching the brain during the operation, is being compared with the standard method using the same threshold for transfusion for all patients. We will use 'near infra-red spectroscopy' (NIRS) to monitor oxygen levels in the brain and help guide surgeons in transfusion decisions. This is a non-invasive technology that is thought to be the best device for measuring oxygen supply.

Who can participate?
Patients over 16 years of age who are having valve or combined valve and coronary surgery at one of three UK hospitals (Bristol Royal Infirmary, Castle Hill Hospital or Glenfield Hospital). We are looking to recruit a total of 150 patients.

What does the study involve?
After you have consented you will be randomly allocated to one of two groups: standard method or new method.
If you are in the standard method group, during surgery, the amount of oxygen being supplied to your body will be monitored in the normal way. Your doctor will take the normal steps to ensure that the oxygen supply is kept at the right levels and you will receive a blood transfusion if your haematocrit falls to the pre-set value normally used at this hospital (23%).
If you are in the new method group, during surgery, the amount of oxygen being supplied to your body will be monitored in the normal way. In addition, we will attach two sensors to the skin on your forehead. These will allow us to monitor the oxygen levels in your brain during surgery. A blood transfusion will only be given if the oxygen level in your brain starts to drop and the doctors cannot improve this using other methods. However, we will not use oxygen levels in the brain as the only guide to transfusion and we will still give you a transfusion if your haematocrit reaches a low level (18%).
Before your operation we will ask you to complete some short questionnaires about your general health. We will also ask you to undergo a series of short tests to check your memory, co-ordination and levels of attention. These tests will in total take about an hour. After heart surgery some patients may become confused and disorientated. We want to find out whether monitoring the level of oxygen in the brain during the operation can reduce these side effects. Patients taking part will be asked to give blood and urine samples. These samples will be tested for several chemicals that will give us an idea of how well different parts of your body, e.g. your brain, heart and kidneys, worked during and after your operation. Blood samples will be taken at six time points and urine samples at four time points during your hospital stay.
Five days after your operation, we will ask you to complete the questionnaires again and to repeat the tests. During your stay in hospital, we may also ask you some short questions about how well your operation wounds are healing. Other information that we need to collect during your hospital stay will be collected from your medical records.
After you are discharged from hospital, we will ask you to complete a short postal questionnaire about your general health, about six weeks after your operation. We will then ask you to attend a special follow-up appointment about three months after your operation. At this visit, we will test your memory, co-ordination and levels of attention again, and ask you to complete the health questionnaires and to answer some other questions about your health since your operation.

What are the possible benefits and risks of participating?
We think that monitoring oxygen levels will help us to ensure better oxygen supply to the brain and other organs. Taking part in the study may change the chance of you having a blood transfusion, depending on the group you are allocated to. We do not think that taking part in this trial will expose you to an increased risk. There is a risk that patients put into the 'standard method' group may experience higher transfusion rates, as well as possibly lower oxygen levels in the tissues. This risk is no different to that experienced by patients undergoing cardiac surgery on a day-to-day basis. The only way that we can be sure that monitoring oxygen levels in the brain is better than the method currently used is by carrying out a study of this kind. As an additional safety measure we have set a minimum haematocrit level (18%) for patients cared for using the 'new method'. If this level is reached, patients will receive a blood transfusion even if oxygen levels in the brain are normal. This minimum haematocrit level is routinely used in some hospitals in the UK and elsewhere. We have done this to avoid any patient having a very low haematocrit, which might be harmful.

Where is the study run from?
The main site is Bristol Heart Institute. The additional sites are Castle Hill Hospital and Glenfield Hospital.

When is the study starting and how long is it expected to run for?
The study started in December 2009. We expect to recruit the final patient in December 2013.

Who is funding the study?
NHS National Institute for Health Research.

Who is the main contact?
Prof Barney Reeves
barney.reeves@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Barney Reeves

ORCID ID

Contact details

Bristol Heart Institute
University of Bristol
Level 7
Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CS/2008/3057

Study information

Scientific title

Patient-specific cerebral oxygentation monitoring as part of an algorithm to reduce transfusion during heart valve surgery: a randomised controlled trial

Acronym

PASPORT

Study hypothesis

The hypothesis for the trial is that a patient-specific, goal-directed algorithm (based on optimising regional cerebral oxygen saturation), combined with a pre-specified "restrictive" haematocrit transfusion threshold of 18, will result in fewer red blood cell (RBC) transfusions and will reduce complications arising from unnecessary transfusion and from low oxygen levels during cardiopulmonary bypass, when compared with the currently used "generic" algorithm for monitoring and optimising oxygen levels.

On 17/11/10 this record was extensively updated to reflect the amendment to the protocol approved by the Research Ethics Committee on 09/11/09. Two further amendments do not affect the information shown on this record.
Please also note that the start and end dates of this trial have been extended from 10/04/09 and 30/09/10 to 01/12/09 and 31/12/12, respectively

On 09/08/2011 updates were made to this trial after further protocol amendments. The study has changed from a single-centre to multi-centre trial following the addition of Castle Hill Hospital.

On 28/11/2012 the overall trial end date was updated from 31/12/2012 to 30/04/2014.

On 08/08/2013, the target number of participants was changed from 150 to 200. Recruitment has been extended until end of December 2013 with final follow-up of the last patient taking place in April 2014.

Ethics approval

The local Research Ethics Committee (REC) approved on 15/06/2009. Amendments to the protocol were approved on 09/11/2009, 19/01/2010,12/02/2010, 17/05/2011 and 27/07/2011. Amendment 9 approved by REC on 24/08/2012. Amendment 10 was approved on 07/08/2013. Amendment 11 was approved on 17/07/2015.

Study design

Randomised controlled multi-centre 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

Oxygen monitoring/blood transfusion in patients having heart valve replacement surgery

Intervention

The trial will compare two different algorithms for optimising tissue oxygenation during cardiopulmonary bypass (CPB), as follows:

1. "Generic algorithm" (including a standard transfusion threshold):
A generic algorithm for optimising tissue oxygenation based on global measures of oxygen utilisation and including a pre-defined intraoperative haematocrit transfusion threshold of 23 (current "standard practice", i.e. our existing protocol).

2. "Patient-specific algorithm" (including a restrictive transfusion threshold):
A patient-specific, goal-directed, algorithm based on monitoring and optimisation of regional cerebral oxygen saturation, combined with a predefined "restrictive" intraoperative haematocrit transfusion threshold of 18 (experimental arm).

Intervention type

Procedure/Surgery

Phase

Not Applicable

Drug names

Primary outcome measures

Current primary outcome measures as of 12/08/2015:
Cognitive function:
Recommended cognitive domains will be tested as follows:
1. Verbal memory: Rey Auditory Verbal Learning Test (AVLT)
2. Attention: First trial of the AVLT, Sustained and divided attention: Trail- Making Test parts A and B
3. Visuo-spatial: Block Design from the Wechsler Adult Intelligence Scale - Revised (WAIS-R) test
4. Motor coordination: Grooved Pegboard Test, dominant and non dominant hand
5. Executive function/Verbal fluency: Controlled Oral Word Association Test (COWAT)

Primary outcome measures from 17/11/2010 to 12/08/2015:
1. Cognitive function: recommended cognitive domains will be tested as follows:
1.1. Verbal memory: Rey Auditory Verbal Learning Test (AVLT)
1.2. Attention: First trial of the AVLT, Sustained and divided attention: Trail- Making Test parts A and B
1.3. Visuo-spatial: Block Design from the Wechsler Adult Intelligence Scale - Revised (WAIS-R) test
1.4. Motor coordination: Grooved Pegboard Test, dominant and non dominant hand
1.5. Executive function/Verbal fluency: Controlled Oral Word Association Test (COWAT)
2. Infectious complications: a cumulative infection score will be calculated by supplementing data on wound infections (the ASEPSIS score that describes signs and symptoms of wound infection on a continuous scale) with data describing the severity of sepsis

Primary outcome measures at time of registration:
1. Cognitive function: recommended cognitive domains will be tested as follows:
1.1. Verbal memory: Rey Auditory Verbal Learning Test (AVLT)
1.2. Attention: First trial of the AVLT, Sustained and divided attention: Trail- Making Test parts A and B
1.3. Psychomotor speed: Digit Symbol Test from the Weschler Adult Intelligence Scale - Revised (WAIS-R) test
1.4. Motor coordination: Grooved Pegboard Test, dominant and non dominant hand
1.5. Executive function/Verbal fluency: Controlled Oral Word Association Test (COWAT)
2. Infectious complications:
2.1. Septicaemia
2.2. Lower respiratory tract infection
2.3. Urinary sepsis
2.4. Wound infection

Secondary outcome measures

Current secondary outcome measures as of 12/08/2015:
1. Units of RBC and other blood components transfused during the operative period and post-operative hospital stay
2. Cerebral oxygenation during the operative period
3. Oxygen delivery and utilisation during CPB
4. Euroqol EQ-5D at baseline and 6 weeks and 3 months after surgery
5. Length of intensive care unit (ICU)/high dependency unit (HDU) stay
6. Length of hospital stay
7. Clinical outcomes (defined as: stroke, ST elevation myocardial infarction, post-operative acute kidney injury, respiratory complications) during the post-operative hospital stay
8. Cumulative resource use, cost and cost-effectiveness
9. All-cause mortality within 30 days of surgery
10. Biochemical markers of organ injury during first 96 hours post-surgery
11. The occurrence of an infectious complication

Secondary outcome measures from 17/11/2010 to 12/08/2015:
1. Units of RBC and other blood components transfused during the operative period and post-operative hospital stay
2. Cerebral oxygenation during the operative period
3. Oxygen delivery and utilisation during CPB
4. Euroqol EQ-5D at baseline and 6 weeks and 3 months after surgery
5. Length of intensive care unit (ICU)/high dependency unit (HDU) stay
6. Length of hospital stay
7. Clinical outcomes (defined as: stroke, ST elevation myocardial infarction, post-operative acute kidney injury, respiratory complications) during the post-operative hospital stay
8. Cumulative resource use, cost and cost-effectiveness
9. All-cause mortality within 30 days of surgery
10. Biochemical markers of organ injury during first 96 hours post-surgery

Initial secondary outcome measures at time of registration:
1. Units of RBC and other blood components transfused during the operative period and post-operative hospital stay
2. Cerebral oxygenation during the operative period
3. Oxygen delivery and utilisation during CPB
4. Euroqol EQ-5D at baseline and 6 weeks and 3 months after surgery
5. Length of intensive care unit (ICU)/high dependency unit (HDU) stay
6. Length of hospital stay
7. Clinical outcomes (defined as: stroke, ST elevation myocardial infarction, post-operative renal dysfunction, respiratory complications) during the post-operative hospital stay
8. Cumulative resource use, cost and cost-effectiveness
9. All-cause mortality within 30 days of surgery
10. Biochemical markers of organ injury during first 48 hours post-surgery

Overall trial start date

01/12/2009

Overall trial end date

30/04/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current information as of 17/11/2010:
1. Adults ≥ 16 years of either sex undergoing valve or combined coronary artery bypass graft (CABG) and valve surgery at the Bristol Royal Infirmary
2. Patients giving informed consent to participate and who are suitable for allocation to either transfusion protocol

Initial information at time of registration:
1. Adults (>= 16 years and <80 years) of either sex undergoing valve or combined coronary artery bypass graft (CABG) and valve surgery at the Bristol Royal Infirmary
2. Patients giving informed consent to participate and who are suitable for allocation to either transfusion protocol

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

200

Participant exclusion criteria

Current exclusion criteria as of 09/08/2011:
1. Patients undergoing emergency cardiac surgery (emergency surgery defined as surgery taking place before the end of the same working day as admission).
2. Patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah's Witnesses).
3. Patients who may have higher perioperative haemoglobin requirements (e.g. preoperative ejection fraction < 30%, cerebrovascular occlusive disease [arterial stenosis > 75%] or critical limb ischemia).
4. Patients with congenital or acquired RBC, platelet or clotting factor disorders, (excluding those receiving antiplatelet therapy, warfarin or other systemic oral anticoagulants).
5. Patients with a neurological disorder (e.g. epilepsy, Alzheimer's, dementia and Parkinson's disease)
6. Patients with a diagnosed psychiatric disorder (e.g. schizophrenia, psychosis), drug or alcohol addiction.
7. Patients with an already identified cognitive impairment (e.g. memory and/or attentional deficits) as defined by psychometric assessment or a preoperative Mini-Mental State Examination score < 24 [37].
8. Patients who have previously sustained a stroke, intra-cerebral haemorrhage, acquired brain injury.
9. Patients with a pre-existing inflammatory state (e.g. sepsis, active inflammatory disease including active rheumatoid arthritis, colitis, Lupus, or Crohn's disease. NB consider latter conditions as active conditions when a patient is taking a high dose of oral steroids, for example > 10 mg/day of prednisolone/prednisone).
10. Patients with end stage renal failure or patients who have undergone renal transplantation.
11. Patients unable to complete the cognitive assessments required for the trial e.g. due to language difficulties, visual or hearing impairment.
12. Patients who were unable to give full informed consent for the study (e.g. language difficulties).
13. Patients already participating in another clinical (interventional) study.

Previous exclusion criteria (added 17/11/2010):
1. Patients undergoing emergency cardiac surgery (emergency surgery defined as surgery taking place before the end of the same working day as admission)
2. Patients who are prevented from having blood and blood products according to a system of beliefs (e.g. Jehovah’s Witnesses)
3. Patients who may have higher perioperative haemoglobin requirements (e.g. preoperative ejection fraction < 30%, cerebrovascular occlusive disease [arterial stenosis > 75%] or critical limb ischemia)
4. Patients with congenital or acquired RBC, platelet or clotting factor disorders (excluding those receiving antiplatelet therapy, warfarin or other systemic oral anticoagulants)
5. Patients with neuropsychological impairment as defined by previous psychiatric illness, stroke, intra-cerebral haemorrhage, preoperative Mini-Mental State Examination score >24 [37], and/or alcohol or drug addiction
6. Patients with a pre-existing inflammatory state (e.g. sepsis, active inflammatory disease including active rheumatoid arthritis, colitis, Lupus, or Crohn's disease. NB consider latter conditions as active conditions when a patient is taking a high dose of oral steroids, for example > 10 mg/day of prednisole)
7. Patients with end stage renal failure or patients who have undergone renal transplantation
8. Patients unable to complete the cognitive assessments required for the trial e.g. due to language difficulties, visual or hearing impairment
9. Patients who were unable to give full informed consent for the study (e.g. language difficulties)
10. Patients already participating in another clinical (interventional) study

Initial exclusion criteria at time of registration:
1. Patients who are prevented from having blood and blood products according to a system of beliefs (e.g., Jehovah's Witnesses)
2. Patients who may have higher perioperative haemoglobin requirements (e.g., emergency cases, preoperative ejection fraction <30%, cerebrovascular occlusive disease [arterial stenosis >75%] or critical limb ischaemia)
3. Patients with congenital or acquired RBC, platelet or clotting factor disorders (excluding those receiving antiplatelet therapy, warfarin or other systemic oral anticoagulants)
4. Patients with neuropsychological impairment as defined by previous psychiatric illness, stroke, transient ischaemic attacks, intra-cerebral haemorrhage, preoperative Mini-Mental State Examination score <24, and/or alcohol or drug addiction
5. Patients with a pre-existing inflammatory state (e.g., sepsis, active inflammatory disease)
6. Patients at risk of impaired cerebral autoregulation (e.g., diabetics requiring insulin, patients aged >80 years, untreated malignant hypertension)
7. Patients who were unable to give full informed consent for the study (e.g., learning or language difficulties)
8. Patients already participating in another clinical (interventional) study

Recruitment start date

01/12/2009

Recruitment end date

31/12/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Bristol Heart Institute
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Glenfield Hospital
Department of Cardiothoracic Surgery Groby Road
Leicester
LE3 9QP
United Kingdom

Trial participating centre

Castle Hill Hospital
Department of Anaesthesia Castle Road
HU16 5JQ
United Kingdom

Sponsor information

Organisation

University Hospitals Bristol NHS Foundation Trust (UK)

Sponsor details

Research and Effectiveness Department
Education Centre
Level 3
Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.uhbristol.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR Programme Grant for Applied Research (UK) (ref: RP-PG-0407-10384)

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

2015 protocol in http://www.ncbi.nlm.nih.gov/pubmed/26685289

Publication citations

Additional files

Editorial Notes

21/12/2015: Publication reference added.