Trial Review

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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] 287842 0
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 296727 0
Critically ill patients admitted to the intensive care unit with blood glucose > 8.9mmol/l 296728 0
Condition category
Condition code
Anaesthesiology 296965 296965 0 0
Other anaesthesiology
Metabolic and Endocrine 296966 296966 0 0
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] 293225 0
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] 296653 0
Percentage of time within Target Range (Blood Glucose: 5.5-8.9mmol/l)
Timepoint [1] 296653 0
5 days post commencement of intervention
Primary outcome [2] 296654 0
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] 296654 0
5 days post commencement of intervention
Primary outcome [3] 296655 0
Mean Blood Glucose Level
Timepoint [3] 296655 0
5 days post commencement of intervention
Secondary outcome [1] 319017 0
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] 319017 0
5 days from commencement of intervention
Secondary outcome [2] 319018 0
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] 319018 0
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?
No
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
60
Accrual to date
Final
Recruitment outside Australia
Country [1] 7349 0
Malaysia
State/province [1] 7349 0
Kuala Lumpur/ Selangor

Funding & Sponsors
Funding source category [1] 292426 0
University
Name [1] 292426 0
University of Malaya
Country [1] 292426 0
Malaysia
Primary sponsor type
University
Name
University Malaya
Address
University of Malaya
50603 Kuala Lumpur
Malaysia
Country
Malaysia
Secondary sponsor category [1] 291115 0
None
Name [1] 291115 0
None
Address [1] 291115 0
None
Country [1] 291115 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293886 0
UMMC Medical Ethics Committee
Ethics committee address [1] 293886 0
Pusat Perubatan Universiti Malaya, Lembah Pantai , 59100, Kuala Lumpur
Ethics committee country [1] 293886 0
Malaysia
Date submitted for ethics approval [1] 293886 0
25/08/2015
Approval date [1] 293886 0
17/02/2016
Ethics approval number [1] 293886 0
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 61442 0
Dr Cheng Yee Shin
Address 61442 0
Department of Anaesthesia and Intensive Care,
University of Malaya
50603 Kuala Lumpur
Malaysia
Country 61442 0
Malaysia
Phone 61442 0
+60128382996
Fax 61442 0
Email 61442 0
yscheng@ummc.edu.my
Contact person for public queries
Name 61443 0
Dr Cheng Yee Shin
Address 61443 0
Department of Anaesthesia and Intensive Care,
University of Malaya
50603 Kuala Lumpur
Malaysia
Country 61443 0
Malaysia
Phone 61443 0
+60128382996
Fax 61443 0
Email 61443 0
yscheng@ummc.edu.my
Contact person for scientific queries
Name 61444 0
Dr Foo Li Lian
Address 61444 0
Pusat Perubatan Universiti Malaya, Lembah Pantai , 59100, Kuala Lumpur
Country 61444 0
Malaysia
Phone 61444 0
+60379494422
Fax 61444 0
Email 61444 0
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

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