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Trial registered on ANZCTR


Registration number
ACTRN12620000917932
Ethics application status
Approved
Date submitted
16/06/2020
Date registered
17/09/2020
Date last updated
10/01/2023
Date data sharing statement initially provided
17/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of continuous versus intermittent delivery of enteral feeding on glycaemic control and gastrointestinal response in critically ill patients (CGM-ICU)
Scientific title
The effect of continuous versus intermittent delivery of enteral feeding on glycaemic control and gastrointestinal response in critically ill patients (CGM-ICU)
Secondary ID [1] 301356 0
None
Universal Trial Number (UTN)
Trial acronym
CGM-ICU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critical Illness 317582 0
Condition category
Condition code
Diet and Nutrition 315665 315665 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CGM-ICU study aims to assess the impact of nutrient delivery pattern (continuous versus intermittent) over a 24-hour period on glycaemic control and gastrointestinal function in enterally fed critically ill patients.

A total of 60 ICU patients will be included from the intensive care unit at the Royal Adelaide Hospital. Participants will be randomised to receive a total of 1200 mL of enteral nutrition (EN) gastrically either as intermittent (4 boluses per 24 hours, therefore one bolus of 300 mL/hr every 6 hours; INT) or continuous (total volume spread evenly per hour over 24 hours, therefore 50 mL/hr for 24 hours; CON). Throughout the study arterial blood samples will be collected every 6 hours via an arterial line present for standard care (t=0, 6, 12, and 24 h relative to the initiation of the study). Continuous interstitial glucose concentrations will be measured using a subcutaneous continuous glucose monitor. Postprandial responses will be determined from blood samples taken every 6 hours to assess plasma amino acid profiles, glucose and insulin concentrations, and key gut related-hormone concentrations (GLP-1, GIP, PYY, CCK, C-peptide, glucagon, leptin, and ghrelin).

On the following day, 20 of the included patients will be assessed in a sub study (duration 4 hours), to measure gastric emptying and nutrient absorption following 24 hours of either INT or CON feeding. Patients will be selected if they meet the additional inclusion criteria: Expected to remain ventilated and receiving enteral nutrition, not receiving gastro-kinetic drugs, no prior upper gastrointestinal surgery and no gastrointestinal surgery on this admission. The 4 hour sub study involves measurement of Gastric Emptying (GE), using bedside scintigraphy, and glucose absorption (3-OMG concentrations). Patients will be provided with a 100 mL dose of enteral formulation (same EN as CON and INT feeding) labelled with 20 MBq 99mTc-calcium phytate colloid, and 3g of 3-O-Methyl-D-gluco-pyranose (3-OMG) (a non-absorbable glucose analogue). Scintigraphic images will be acquired at 1-min intervals for 60 min, and 3-min intervals thereafter for a total of 4 hours. Arterial blood samples will be taken starting at t= -5 mins, then every 15 minutes for the first hour (t= 15, 30, 45, 60 min), and half hourly for the remaining 3 hours (t= 90min – 240min).
Intervention code [1] 317655 0
Treatment: Other
Comparator / control treatment
Patients in the control group will receive enteral feed continuously over 24 hours, as is standard care. They will be fed the same volume (1200 mL) and enteral feed type as the intervention group, at a rate of 50 mL per hour.
Control group
Active

Outcomes
Primary outcome [1] 323901 0
Glycaemic variability (coefficient of variation of glucose concentrations in mmol/L measured by Continuous Glucose Monitoring).
Timepoint [1] 323901 0
Over 24 hours (study day 0).
Primary outcome [2] 324667 0
Glycaemic variability (mean and standard deviation of glucose concentrations in mmol/L) measured by Continuous Glucose Monitoring.
Timepoint [2] 324667 0
Over 24 hours (study day 0).
Secondary outcome [1] 383253 0
Mean insulin dose (IU) provided over 24 hours to maintain glycaemic control according to standard care (i.e. Royal Adelaide Hospital Intensive Care Unit protocol: 6.0-10.0 mmol/L). This will be determined from hospital records.
Timepoint [1] 383253 0
The provided insulin dose and glycaemic variability over 24 h of feeding (Day 0) will be calculated.
Secondary outcome [2] 383254 0
Rate of gastric emptying (gastric retention expressed as % over 4 h and 50% of emptying time), measured by scintigraphy. A 100 mL dose of enteral formulation labelled with 20 MBq 99mTc-calcium phytate colloid will be given to patients. This will be determined in the sub-study only (20 patients).
Timepoint [2] 383254 0
Scintigraphic images will be acquired at 1-min intervals for 60 min, and 3-min intervals thereafter for a total of 4 hours (240mins).
Secondary outcome [3] 383255 0
Rate of glucose absorption (AUC of 3-OMG concentrations, peak concentrations, and time to peak), from arterial blood samples.
Timepoint [3] 383255 0
Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [4] 383257 0
Gastric residual volumes (total mL per 24 h period and highest volume per 24 h period). This will involve aspiration of fluid from the feeding tube, every 6 hours, as per clinical practice for patients in the Intensive Care Unit.
Timepoint [4] 383257 0
Gastric residual volume (GRV) will be measured every 6 hours, as per clinical practice (prior to every feeding bolus in the Intermittent group and every 6 hours in the Continuous group) as a measurement for Gastric emptying and to ensure safety.
Secondary outcome [5] 383822 0
Area under the concentration time curves of glucose concentration, from arterial blood samples.
Timepoint [5] 383822 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.
Secondary outcome [6] 383823 0
Area under the concentration time curves of insulin concentration, from arterial blood samples.
Timepoint [6] 383823 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [7] 383824 0
Area under the concentration time curves of c-peptide concentration, from arterial blood samples.
Timepoint [7] 383824 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [8] 383825 0
Area under the concentration time curves of glucagon concentration, from arterial blood samples.
Timepoint [8] 383825 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [9] 383826 0
Area under the concentration time curves of cholecystokinin (CKK) concentration, from arterial blood samples.
Timepoint [9] 383826 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [10] 383827 0
Area under the concentration time curves of peptide YY (PYY) concentration, from arterial blood samples.
Timepoint [10] 383827 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [11] 383828 0
Area under the concentration time curves of glucagon-like peptide-1 (GLP-1) concentration, from arterial blood samples.
Timepoint [11] 383828 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [12] 383829 0
Area under the concentration time curves of gastric inhibitory peptide (GIP) concentration, from arterial blood samples.
Timepoint [12] 383829 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [13] 383830 0
Area under the concentration time curves of grehlin concentration, from arterial blood samples.
Timepoint [13] 383830 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [14] 383831 0
Area under the concentration time curves of leptin concentration, from arterial blood samples.
Timepoint [14] 383831 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [15] 383832 0
Plasma amino acid profiles, from arterial blood samples.
Timepoint [15] 383832 0
Day 0: t=0, 6, 12, and 24 h relative to the initiation of the study.

Day 1 (sub study): t= -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins.
Secondary outcome [16] 384595 0
Area under the concentration time curves of glucose concentration, measured by Continuous Glucose Monitoring.
Timepoint [16] 384595 0
Over 24 hours (study day 0).
Secondary outcome [17] 384597 0
Number and severity of hypoglycaemic events, measured by Continuous Glucose Monitoring.
Timepoint [17] 384597 0
Over 24 hours (study day 0).
Secondary outcome [18] 385368 0
Number and severity of hyperglycaemic events, measured by Continuous Glucose Monitoring.
Timepoint [18] 385368 0
Over 24 hours (study day 0).

Eligibility
Key inclusion criteria
1. Adults (greater than or equal to 18 years)
2. Admitted to Royal Adelaide Hospital (RAH) ICU
3. Receiving or eligible to receive gastric enteral nutrition
4. Expected to be receiving enteral nutrition in ICU until at least the day after tomorrow.
5. Mechanically ventilated
6. Gastrokinetic medications will be held during the study as appropriate in consultation
with treating clinician

Additional inclusion into the sub-study (day 1) (Subset of 20 patients):
1. Expected to be ventilated for >48 hours (At day -1)
2. Expected to be receiving enteral nutrition for >48 hours (At day -1)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treating clinician considers intermittent feeding to be clinically contraindicated (continuous feeding is current practice in the RAH ICU)
2. Death is deemed to be imminent or inevitable during admission and the attending doctor, patient, or substitute decision maker is not committed to active treatment.
3. Diagnosed Diabetes Mellitus (type 1 and type 2)
4. Pregnancy
5. Receiving dialysis

Additional exclusion into sub-study (day 1) (Subset of 20 patients):
1. Gastrointestinal surgery on this admission
2. Previous upper gastrointestinal surgery (oesophageal, stomach or duodenal)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A randomization scheme will be set up prior to the start of the study (using www.randomizer.org) and saved on a password protected file. Allocation will be concealed to all investigators involved in the study up until the day prior to the study, after consent has been granted. An independent researcher will allocate the randomization code and intervention to the included patient and provide this to the investigators.
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
This exploratory proof-of-concept study will provide information on the feasibility of recruitment and study conduct in this population. Based upon a recent study (McNelly et al, Chest 2020) comparing continuous vs intermittent feeding on glycaemic variability (coefficient of variation for plasma glucose concentrations), an effect size of 0.9 is expected in our primary endpoint (glycaemic variability). Moreover, a difference of 20% in our primary outcome will be expected to be clinically relevant. With a power of 0.95 and a<0.05, we will need to 28 patients in each study group to include a total of 56 patients. We will aim to recruit 80 patients to allow for a dropout rate and protocol violations (common in many critical care trials) of ~30%, with increased recruitment allowed to ensure equal numbers per arm. It is anticipated that 60 patients can be recruited over 12 months to assess the primary outcome, and a subset of 20 patients to assess secondary parameters.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2020
Actual
19/10/2020
Date of last participant enrolment
Anticipated
Actual
15/03/2022
Date of last data collection
Anticipated
31/07/2022
Actual
16/03/2022
Sample size
Target
80
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 16751 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 30363 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 305796 0
Hospital
Name [1] 305796 0
in kind funding in the form of staff time from the Intensive Care Unit Research Royal Adelaide Hospital
Country [1] 305796 0
Australia
Funding source category [2] 306659 0
Government body
Name [2] 306659 0
Netherlands Organisation for Health Research and Development
Country [2] 306659 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital.
Address
Royal Adelaide Hospital,
Port road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 307312 0
None
Name [1] 307312 0
Address [1] 307312 0
Country [1] 307312 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306067 0
Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)
Ethics committee address [1] 306067 0
Ethics committee country [1] 306067 0
Australia
Date submitted for ethics approval [1] 306067 0
21/05/2020
Approval date [1] 306067 0
23/06/2020
Ethics approval number [1] 306067 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102582 0
Dr Imre Kouw
Address 102582 0
Adelaide Health and Medical Sciences
University of Adelaide
4 North Terrace, Adelaide SA 5000
Country 102582 0
Australia
Phone 102582 0
+61 4 06 979 121
Fax 102582 0
Email 102582 0
[email protected]
Contact person for public queries
Name 102583 0
Lee-anne Chapple
Address 102583 0
Intensive Care Research
Royal Adelaide Hospital
Port Road, Adelaide 5000, South Australia
Country 102583 0
Australia
Phone 102583 0
+61870741763
Fax 102583 0
Email 102583 0
[email protected]
Contact person for scientific queries
Name 102584 0
Imre Kouw
Address 102584 0
Adelaide Health and Medical Sciences
University of Adelaide
4 North Terrace, Adelaide SA 5000
Country 102584 0
Australia
Phone 102584 0
+61 4 06 979 121
Fax 102584 0
Email 102584 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.