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Trial registered on ANZCTR

Registration number

ACTRN12616001450404

Ethics application status

Approved

Date submitted

19/11/2015

Date registered

17/10/2016

Date last updated

17/10/2016

Type of registration

Retrospectively registered

Titles & IDs

Public title

Comparing glucose control in the critically ill patient through two methods - conventional insulin sliding scale as compared to computerised automated insulin delivery ( enhanced model predictive control).

Scientific title

Efficacy of enhanced model predictive control (eMPC) in insulin therapy in the critically ill

Secondary ID [1]

nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

severe sepsis and septic shock

Critically ill patients admitted to the intensive care unit with blood glucose > 8.9mmol/l

Condition category

Condition code

Anaesthesiology

Other anaesthesiology

Metabolic and Endocrine

Other metabolic disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This is a randomised controlled trial.

The objective of this trial is to compare the efficacy between the delivery of insulin via the eMPC model (through a Space Glucose Device) and delivery of insulin via conventional infusion method with the usage of insulin sliding scale, in regards to glucose control.

The Space GlucoseControl Device is a Class IIb medical device. It is a device manufactured by B Braun. The Space GlucoseControl device is a decision support system that calculates an optimum level of insulin dosing. It consists of 3 infusion pumps, 2 for enteral and parenteral nutrition, and 1 for insulin. The system automatically records information from the nutrition pumps including current status of infusion, bolus doses and carbohydrate intake. It combines this information with manually-entered blood glucose measurements, administered insulin doses and patient-specific data, such as previous response to insulin. A proprietary computer algorithm in the system, called the enhanced model predictive control (eMPC) algorithm, then predicts the future blood glucose curve and calculates the best insulin dose rate to keep blood glucose within the range sprecified by the clinician responsible for the patient's care. Based on the algorithm prediction, the Space GlucoseControl system calculates the time interval to the next blood glucose measurement and gives and audio-visual alarm to alert nursing staff when it is due.

A total of 60 patients will be recruited for this trial. The patients recruited are critically ill adult patients with severe sepsis or septic shock; and with a blood glucose of more than 8.9mmol/l upon admission to ICU. The blood glucose target is aimed to be 5.5-8.9mmol/l.. Patients recruited for the trial will be radomised into two groups.

The first group will have insulin delivered via the Space ClucoseControl Device (which uses the eMPC algorithm). Upon commencement of the insulin therapy, baseline blood glucose will be measured and recorded, with the insulin infusion commenced at the rate recommended by the device. Based on the eMPC algorithm prediction, the device calculates the time interval to the next blood glucose measurement and alerts the nursing staff to check the blood glucose level and adjust the insulin delivery accordingly. The time interval for blood sampling ranges from 30minutes to 4 hours depending on the algorithm. If patient is started on enteral and parenteral nutrition, the date is also entered into the device and adjustments in delivery would be made after calculations are made based on the algorithm. All trial related activities and data will be carried out until the completion of 5 days. After 5 days, if patient still requires insulin therapy, they would be switched to conventional insulin infusion with Insulin Sliding Scale.

The second group of patients will be randomized into the group with insulin delivery via conventional method, with the aid of Insulin Sliding Scale. The rate of infusion of insulin would be determined by the scale. Monitoring of blood glucose would be hourly upon commencement, and the interval would be increased to 2-4hours (when there is no rate change in 2 consecutive hours), and adjustments for the infusion rate is made manually, and according to the Insulin Sliding Scale selected. All trial related activities and data will be collected for 5 days. Upon completion of 5 days, if patient still requires insulin infusion, it would still be continued for the patient.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

The control/comparator group will have the conventional method of glucose control, with the aid of Insulin Sliding Scale to target the blood glucose at 5.5-8.9mmol/l. The rate of infusion of insulin would be determined by the scale. Monitoring of blood glucose would be hourly upon commencement, and the interval would be increased to 2-4hours (when there is no rate change in 2 consecutive hours), and adjustments for the infusion rate is made manually, and according to the Insulin Sliding Scale selected.
Monitoring of blood glucose in this group is done by study nurses and clinician.

Control group

Active

Outcomes

Primary outcome [1]

Percentage of time within Target Range (Blood Glucose: 5.5-8.9mmol/l)

Timepoint [1]

5 days post commencement of intervention

Primary outcome [2]

Time to achieve target range. This outcome is assessed by the duration (in hours) required upon commencement of the insulin treatment to achieve the desired blood glucose range.

Timepoint [2]

5 days post commencement of intervention

Primary outcome [3]

Mean Blood Glucose Level

Timepoint [3]

5 days post commencement of intervention

Secondary outcome [1]

Correlation between blood glucose level, blood glucose control and IL-6
(Blood glucose level would be measure with a point-of care glucose meter with arterial blood samples. Blood IL-6 level would be determined by chemiluminescent enzyme immunoassay method)

Timepoint [1]

5 days from commencement of intervention

Secondary outcome [2]

Nursing Satisfaction
( A survery form with 5 level Likert Scale would be given to the nurses to fill in at the end of the study to assess the outcome)

Timepoint [2]

10months after commencement of the study/ Completion of recruitment for the study

Eligibility

Key inclusion criteria

Severe Sepsis or Septic Shock
Adult patients (>18 years old)
Blood Glucose level >8.9mmol/l upon admission OR
Already on insulin therapy
ICU admission expected to be more than 5days

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Known allergy to Insulin,
Diabetic Ketoacidosis
Hyperosmolar Hyperglycaemic Syndrome

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)

Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by computer software

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

To determine sample size for this study we use power study. To prove the sample size adequacy for a study this is a very useful and frequently used tool in medical research. The prevalence of severe sepsis patients in PPUM Malaysia is 25.9 percent (ref, Malaysian Registry of Intensive Care ). Since our population size is unknown, to obtain an appropriate sample size from this population, we use the following formula:
n= (Z1-Beta)2[p(1-p)]/d2
Where:
n = required sample size
Z1-Beta = Z value at power 1-Beta (at power 80% this value is 0.84)
p = referred prevalence for the study (0.259)
d = margin of error (ideal value is 0.05 for estimated proportions in the range of 20%-80%) (Gorstein et al., 2007)
Considering 80% power of test, 5% marginal error and 25.9% prevalence rate, the formula gave us a sample size of 54.17. Finally we use 60 samples for our study.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

1/04/2016

Date of last participant enrolment

Anticipated

31/12/2017

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Malaysia

State/province [1]

Kuala Lumpur/ Selangor

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Malaya

Address [1]

University of Malaya
50603 Kuala Lumpur
Malaysia

Country [1]

Malaysia

Primary sponsor type

University

Name

University Malaya

Address

University of Malaya
50603 Kuala Lumpur
Malaysia

Country

Malaysia

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

UMMC Medical Ethics Committee

Ethics committee address [1]

Pusat Perubatan Universiti Malaya, Lembah Pantai , 59100, Kuala Lumpur

Ethics committee country [1]

Malaysia

Date submitted for ethics approval [1]

25/08/2015

Approval date [1]

17/02/2016

Ethics approval number [1]

20158-1588

Summary

Brief summary

In the pathophysiology of sepsis, pro-inflammatory cytokines including IL-6, IL-1, TNFa are known to play a pivotal role, and an overproduced cytokines enter into the bloodstream causing hypercytokinaemia, which leads to organ failure via humoral mediator network activation and vascular endothelial damage. This overwhelming production of mediators such as pro- and anti-inflammatory cytokines can cause different kinds of metabolic derangements such as hyperglycemia. Hyperglycemia in the hospital, whether in patients with known diabetes or with a temporary hyperglycaemic state due to stress, is known to be associated with poor outcome such as prolonged hospitalization, increased rates of infection, and in-hospital death. In the years 2001, 2006 and 2009, three large randomized controlled single centre trials in three different intensive care departments have shown that normalized glucose level would lead to a significant reduction of in-hospital mortality and morbidity. Insulin Therapy (IT) has been characterized as an important treatment option to substantially improve outcome in medical and surgical patients in adult ICUs.

The blood sugar management has been a challenging, complex and time consuming task that requires nurses with enough experience and knowledge. The common method was based on a paper based protocol for manual intensive insulin therapy, which is-Sliding scales. Often, the required dosage of insulin is estimated rather than determined according to objective criteria. Therefore, lethal consequences, in the form of hypoglycaemia, can occur due to false estimations under certain circumstances. 

eMPC (enhanced model predictive control) is a computer-based decision support system which helps to achieve accurate  and  reliable blood glucose control in the desired ranges. Information on parenteral and enteral nutrition is automatically integrated in the calculations. The algorithm may help to overcome some of the limitations in current practice by aiding physicians in the decision making process. The eMPC (enhanced model predictive control) algorithm has been successfully tested in several clinical trials involved more than 200 patients.

We thus aim to undertake a prospective, randomized, open label single-center study to investigate the effectiveness of the eMPC algorithm in local adult medical ICU patients. The correlation between blood IL-6 level and blood glucose control in patients with sepsis will also be investigated.

Trial website

Trial related presentations / publications

Public notes

The written letter of approval was only available later as there were a few amendments to make on the consent form.

Contacts

Principal investigator

Name

Dr Cheng Yee Shin

Address

Department of Anaesthesia and Intensive Care,
University of Malaya
50603 Kuala Lumpur
Malaysia

Country

Malaysia

Phone

+60128382996

Fax

yscheng@ummc.edu.my

Contact person for public queries

Name

Cheng Yee Shin

Address

Department of Anaesthesia and Intensive Care,
University of Malaya
50603 Kuala Lumpur
Malaysia

Country

Malaysia

Phone

+60128382996

Fax

yscheng@ummc.edu.my

Contact person for scientific queries

Name

Foo Li Lian

Address

Pusat Perubatan Universiti Malaya, Lembah Pantai , 59100, Kuala Lumpur

Country

Malaysia

Phone

+60379494422

Fax

li_lian@ummc.edu.my

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

No additional documents have been identified.

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