Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Mr D Pagano


Contact details

Cardiac Surgery
Queen Elizabeth Hospital
B15 2TH
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title


Study hypothesis

This study assesses the effect of supplementing naturally-occurring insulin and energy sources (glucose) on heart protection during aortic valve replacement surgery. These treatments have a sound experimental basis for improving outcome. If this improvement is confirmed surgical results could be materially improved. We will be studying heart function, heart muscle energy stores and chemicals which quantify the amount of heart muscle injury.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

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


Aortic valve replacement


On the morning of surgery patients will be randomised to one of two groups. There are 2 groups of patients in this trial, allocated to receive placebo or G.I.K.
1. Group A. receive dextrose 5% run at 0. 75ml/kg/h rounded to the nearest 10 mls/hr starting at sternotomy and finishing 6 hours following release of the aortic cross clamp.
2. Group B: a central intravenous G.I.K. ( 500 ml of 40% glucose 35 units insulin 50 mmols of KC1) run at 0. 75 mis/kg/hr rounded to the nearest 10 mls/hr starting at sternotomy and finishing 6 hours following release of the aortic cross clamp.

Blood for baseline CKMB and cTnI will be drawn for centrifuge and storage and arterial blood gases ( ABC) will be withdrawn for immediate analysis in the anaesthetic room before standard induction using the arterial line routinely inserted before induction of anaesthesia additional) . Alter induction a pulmonary artery balloon flotation catheter will be positioned in the anaesthetic room and the patient then transferred to the operating room ( normal clinical practice or additional). Approximately 40% have such catheters placed routinely for clinical reasons - in the study they will be used in every patient).

Baseline cardiac output studies, pulmonary capillary wedge pressures ( normal clinical practice in the patients or additional).

Surgery will proceed as normal with 1/2 hourly K+ and blood glucose sampling pre-CPB, 20 minutely during CPB and 1 hourly post CPB with protocol based management of blood glucose and potassium. The protocol is based on that used in the DIGAMI study (additional).

Anaesthetic and CPB management will be standardized to control for known factors affecting outcome including pH management, C02 control, re-warming protocols etc. Myocardial protection will be afforded by cold blood cardioplegia. Criteria for the initiation of inotropic or other support will be standardized. Ventilator weaning criteria are standard (normal clinical practice).

During the conduct of the operation in certain cases, the surgeon will place a monitoring cannula in the coronary sinus under direct vision. Such placement is a standard technique for administration of retrograde cardioplegia. In this study it will be placed to undertake oximetric measurement and will be removed at the end of cardiopulmonary bypass. Its insertion and removal are performed under direct vision. The risk associated with this procedure is minimal and should be no greater than the risk of pulmonary flotation catheter insertion (i.e.1:15000 adverse events) (additional).

Myocardial biopsies for will be performed just prior to aortic cross clamp application, just prior to aortic cross clamp release and after 10 minutes of reperfusion. Myocardial diopsies will be snap frozen and stored as mentioned above (additional). In addition a small amount of epicardial and thigh fat and rectus abdominis muscle (pea size) will be removed at approximately the same time. These will be taken from exposed sites through the sternotomy and long saphenous vein harvest sites (additional).

Intervention type



Not Specified

Drug names

Primary outcome measure

Not provided at time of registration

Secondary outcome measures

Not provided at time of registration

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Patients eligible for entry into the trial will be consulted and recruited in:
1. Pre-surgical consultation clinic
2. Pre-admission clinic
3. During hospital admission for surgery

Before surgery they will have an echocardiogram/MRI scan to assess left ventricular hypertrophy. 2D directed M-mode echocardiography will be used to determine LV mass using the anatomically-validated cube formula. Consistency will be cross-checked using LV mass quantification from the area-length 2D method. There is no risk associated with transthoracic echocardiography. A subset of subjects will also undergo LV mass assessment using MRS. LV mass will be calculated using serial contiguous short axis TrueFISP cine sequences with 7mm slice thickness and 3mm gap using a 1. 5-Tesla magnet. Analysis will be performed off-line using Siemens ARGOS software. There is no biological risk to MR scanning, although patients with ferromagnetic material within the body have to be excluded (the most common example is that of older cerebral aneurysm clips).

Participant type


Age group




Target number of participants

Not provided at time of registration

Participant exclusion criteria

Patients with ferromagnetic material within the body.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Cardiac Surgery
B15 2TH
United Kingdom

Sponsor information


Department of Health

Sponsor details

Richmond House
79 Whitehall
United Kingdom
+44 (0)20 7307 2622

Sponsor type




Funder type


Funder name

University Hospital Birmingham NHS Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

NHS R&D Support Funding

Alternative name(s)

Funding Body Type

Funding Body Subtype


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

Basic results (scientific)

Publication list

1. 2011 results in

Publication citations

  1. Results

    Howell NJ, Ashrafian H, Drury NE, Ranasinghe AM, Contractor H, Isackson H, Calvert M, Williams LK, Freemantle N, Quinn DW, Green D, Frenneaux M, Bonser RS, Mascaro JG, Graham TR, Rooney SJ, Wilson IC, Pagano D, Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial., Circulation, 2011, 123, 2, 170-177, doi: 10.1161/CIRCULATIONAHA.110.945170.

Additional files

Editorial Notes