Condition category
Surgery
Date applied
30/09/2005
Date assigned
30/09/2005
Last edited
08/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
A coronary artery bypass graft (CABG) is a surgical procedure to treat coronary heart disease. During the procedure, the patient’s blood may be re-routed to a heart-lung bypass machine (cardiopulmonary bypass [CPB]). CABG involves periods when the blood supply to the heart tissue is interrupted (ischaemia) and then returns (reperfusion), which may injure the heart tissue (ischemic reperfusion injury). High pressure (hyperbaric) oxygen treatment has been found to reduce heart injury and improve heart function after a heart attack. The aim of this study is to determine whether preconditioning coronary heart disease patients with hyperbaric oxygen before they undergo CPB CABG surgery leads to improved heart function after the operation. We will also assess the safety of hyperbaric oxygen preconditioning, its effects on heart injury, and how long patients need to stay in the intensive care unit (ICU) after the operation.

Who can participate?
Patients undergoing first-time elective CPB CABG surgery

What does the study involve?
Participants are randomly allocated to either be treated with hyperbaric oxygen or not. Treatment with hyperbaric oxygen was completed about 2 hours before the operation. Blood and heart tissue samples (biopsies) are collected during the operation to assess heart injury and the degree of heart protection provided by the hyperbaric oxygen preconditioning. We also record any adverse events and the number of days patients spend in the ICU after the operation.

What are the possible benefits and risks of participating?
Possible benefits of participation include reduced complications after CABG surgery. Risks of participation include complications from treatment with hyperbaric oxygen such as earache, nausea and vomiting.

Where is the study run from?
Castle Hill Hospital (UK)

When is the study starting and how long is it expected to run for?
August 2004 to June 2006

Who is funding the study?
The North and South Bank Research and Development Consortium (UK), NHS R&D Support Funding

Who is the main contact?
Dr Jeysen Yogaratnam
jeysenzy@msn.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Jeysen Yogaratnam

ORCID ID

Contact details

Department of Cardiothoracic Surgery
Castle Hill Hospital
Castle Road
Cottingham
Hull
HU16 5JQ
United Kingdom
+44 (0)1482 875875 (Bleep 725)
jeysenzy@msn.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0084151415

Study information

Scientific title

The effects of neo-adjuvant hyperoxic hyperbaric preconditioning on myocardial protection & ischaemic reperfusion injury

Acronym

Study hypothesis

Does treatment with high pressure (hyperbaric) oxygen (hyperbaric preconditioning), as opposed to short intraoperative episodes of no flow of blood followed by flow of blood to the heart (ischemic preconditioning), provide effective protection to the heart against the phenomenon of ischemic reperfusion injury (injury that occurs to tissues that experience a flow of blood following a prolonged period of no flow of blood) that is known to occur after on-pump and off pump coronary artery bypass surgery?

Ethics approval

Not provided at time of registration

Study design

Prospective double-blind 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

Surgery: Coronary artery bypass grafting (CABG)

Intervention

Patients will be recruited from the cohort of the 4 surgeons at the Cardiothoracic Unit in Castle Hill Hospital. Patients will be recruited at the Out-Patients Clinic and on the ward prior to surgery following explanation of the study to the patient and informed consent being obtained.

In order to prevent patients from comparing treatment modalities among themselves and causing patient-induced bias, the patient will not be aware if he/she is to receive ischemic preconditioning. The surgeon and the investigator will be aware of who is to receive ischemic preconditioning prior to surgery.

The patient, the surgeon and the investigator will not be aware of who is to receive hyperbaric oxygen preconditioning or normal atmospheric air prior to surgery. This double blinding is done to further reduce the study bias.

Randomisation will be done in groups of patients. Patients will initially be randomised as a group as to whether they receive ischemic preconditioning or not. After a group of patients have been randomised to either ischemic preconditioning or not, that group will be further randomised as to whether they receive pre-operative hyperbaric oxygen or atmospheric air in a hyperbaric chamber.

The 128 patients will be divided into 2 groups, 64 in each group ie. Group A (64 patients) and Group B (64 patients). Group A (64 patients) will consist of patients undergoing on-pump coronary artery bypass graft surgery. Group B (64 patients) will consist of patients undergoing off-pump coronary artery bypass graft surgery.
The surgeon will determine if the patients has coronary artery bypass graft surgery on-pump or off-pump.

Each of the 64 patients in Group A and Group B, will randomly be further divided into 2 separate groups of 32 patients each ie. Group A1 (32 patients), Group A2 (32 patients), Group B1 (32 patients) and Group B2 (32 patients). The 32 patients in Group A1 and B1 will be treated with ischemic preconditioning while the 32 patients in group A2 and B2 will not be treated with ischemic preconditioning.

Each of the 32 patients in Group A1, A2, B1 and B2 will randomly be further divided into 2 separate groups of 16 patients each ie. Group A1Omega (16 patients), Group A1Teta (16 patients), Group A2Omega (16 patients), Group A2Teta (16 patients), Group B1Omega (16 patients), Group B1Teta (16 patients), Group B2Omega (16 patients) and Group B1Teta (16 patients). Each of the 16 patients in the Omega groups will receive hyperbaric oxygen preconditioning while each of the 16 patients in the Teta groups will not receive hyperbaric oxygen preconditioning (ie. they will receive atmospheric air in a hyperbaric chamber).

Therefore, there will be 8 subgroups. Group A1Omega (16 patients) will receive hyperbaric preconditioning and ischemic preconditioning and operated on-pump. Group A1Teta (16 patients) will not receive hyperbaric preconditioning but will receive ischemic preconditioning and will be operated on-pump. Group A2Omega (16 patients) will receive hyperbaric preconditioning but will not receive ischemic preconditioning and will be operated on-pump. Group A2Teta (16 patients) will not receive hyperbaric preconditioning or ischemic preconditioning and will be operated on-pump. Group B1Omega (16 patients) will receive hyperbaric preconditioning and ischemic preconditioning and will be operated off-pump. Group B1Teta (16 patients) will not receive hyperbaric preconditioning but will receive ischemic preconditioning and will be operated off-pump. Group B2Omega (16 patients) will receive hyperbaric preconditioning but will not receive ischemic preconditioning and will be operated off-pump. Group B2Teta (16 patients) will not receive hyperbaric preconditioning or ischemic preconditioning and will be operated off-pump.

Intervention type

Procedure/Surgery

Phase

Not Specified

Drug names

Primary outcome measures

Demonstration of anticipated enhanced protective effect of hyperbaric preconditioning in the heart biopsies as determined by
1. Elevated levels of cellular HSP 72 mRNA, HSP 72 protein
2. Elevated levels of cellular iNOS mRNA, iNOS protein, eNOS mRNA, eNOS protein and total cellular Nitric Oxide
3. Reduced ischemic reperfusion injury as determined by reduced levels of P-selectin, TNF-ALPHA, IL-6 and IL-8 and its mRNA ie. P-selectin mRNA, TNF-ALPHA mRNA, IL-6 mRNA and IL-8 mRNA

Secondary outcome measures

Not provided at time of registration

Overall trial start date

31/08/2004

Overall trial end date

08/06/2006

Reason abandoned

Eligibility

Participant inclusion criteria

Patients will be recruited from the cohort of the 4 surgeons at the Cardiothoracic Unit in Castle Hill Hospital.

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

128

Participant exclusion criteria

1. Asthma
2. Known intolerance to N acetyl cysteine
3. Serum creatinine greater than 200 mol/L

Recruitment start date

31/08/2004

Recruitment end date

08/06/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Castle Hill Hospital
Hull
HU16 5JQ
United Kingdom

Sponsor information

Organisation

Department of Health

Sponsor details

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Funder name

The North and South Bank Research and Development Consortium (UK), NHS R&D Support Funding

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

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20129356

Publication citations

  1. Results

    Yogaratnam JZ, Laden G, Guvendik L, Cowen M, Cale A, Griffin S, Hyperbaric oxygen preconditioning improves myocardial function, reduces length of intensive care stay, and limits complications post coronary artery bypass graft surgery, Cardiovasc Revasc Med., 2010, 11, 1, 8-19, doi: 10.1016/j.carrev.2009.03.004.

Additional files

Editorial Notes

08/04/2016: Plain English summary added.