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Trial registered on ANZCTR


Registration number
ACTRN12616000212459
Ethics application status
Approved
Date submitted
15/02/2016
Date registered
17/02/2016
Date last updated
17/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A multicenter randomized controlled trial comparing intermittent enteral feeding while in right lateral tilt position to standard care among mechanically ventilated adult Intensive Care Unit (ICU) patients
Scientific title
A multicenter randomized controlled trial comparing intermittent enteral feeding while in right lateral tilt position to standard care among mechanically ventilated adult ICU patients
Secondary ID [1] 288543 0
Nil known
Universal Trial Number (UTN)
U1111-1173-5846
Trial acronym
ICU-FM Study
(ICU Feeding-Mode Study )
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult critically ill patients requiring invasive mechanical ventilation 297646 0
Condition category
Condition code
Respiratory 297834 297834 0 0
Other respiratory disorders / diseases
Diet and Nutrition 297843 297843 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will compare a strategy of intermittent enteral feeding while in right lateral tilt position (intervention) to the current standard practice of continuous enteral feeding (control) among mechanically ventilated patients in ICU. The choice of feeding bag/formulae, ‘target daily feed volume’ and target continuous infusion rate will be determined as per standard practice or at the discretion of the treating clinician. The ‘target daily feed volume’ will be derived as a product of target continuous infusion rate and the number of hours left in the day (maximum 24 hours). The ‘bolus target’ volume in the intermittent feeding arm will be one-third of the target daily feed volume, and must not exceed 10 ml/kg unless reviewed by the clinician. Patients will have routine posture turns every 3-4 hours as per the standard nursing practice in both arms. The study intervention period is for the duration that a patient require enteral feeding via the gastric feeding tubes while in ICU.

Signs of feed intolerance (such as vomiting, oral regurgitation of gastric contents, abdominal pain or tenderness, distension, inability to pass flatus >3 days or abnormal abdominal imaging) and volume of gastric aspirates will be monitored in both arms as per standard practice. If feeding is well tolerated and the gastric aspirate volume is low (<150 ml), then the subsequent feed rate (in the standard arm) or bolus feed volume (in the intermittent arm) should be increased in incremental steps (100 to 150 ml) to gradually achieve the target rate or the target volume. In other words, the subsequent bolus feed volume in the intermittent arm will gradually and incrementally go up only if a patient shows none of the six signs of feed intolerance mentioned above, and has low gastric aspirates (<150 ml). In addition, the protocol is pragmatic and allows clinicians and the unit dietitian to adjust bolus volumes as deemed suitable. The use of pro-kinetic agents will be as per the discretion of the treating clinician in both arms in response to either feed intolerance or large gastric aspirates.

The patients in the intervention group will be fed thrice a day with up to one-third of the target feed volume for the day infused within one hour each time. The patients will be nursed in routine semi-recumbent right lateral tilt position (or sitting upright position if out of bed) during the feeding hour and for another two hours post-feeding. The recommended feed times are 5-6 am, 12-1 pm and 8-9 pm, but these timings can be adjusted by the bedside nurse if deemed appropriate. This imply that each day patients in the interventional arm would spend 3 hours thrice a day in right lateral tilt position during feed times and rest of the 15 hours would be spent in supine or left lateral tilt position at the discretion of the bedside nurse. If a patient is being initiated on intermittent enteral feeding for the first time, then the volume of the first feed will be 150 ml, and the subsequent feed volumes will be titrated, in incremental steps until bolus target is attained, according to feed tolerance and volume of gastric aspirates.

For all the study patients, gastric tube must be aspirated just before any scheduled upper airway or upper GI procedure. Feeds should restart after the procedure as per the current standard practice if and when there are no medical contraindications. For patients in the intervention group, feed timings can be adjusted at the discretion of the bedside nurse so that the patient do not receive any enteral feeds at least 4 hours before any scheduled upper airway or upper GI procedures.
Intervention code [1] 293921 0
Prevention
Comparator / control treatment
The patients in the control group will be fed as per the current standard practice at each center. The standard practice at all centers is continuous enteral feeding for up to 24 hours a day..
Control group
Active

Outcomes
Primary outcome [1] 297364 0
Incidence rate of gastrointestinal intolerance (a composite outcome of vomiting*, diarrhoea** or constipation***; which would be assessed on review of medical records and with the help of a bedside vomiting and diarrhoea nursing observation chart):

* Vomiting will be defined as gastric contents detected in or outside oral cavity, including spontaneous regurgitation of enteral feeds, but not the regurgitation associated with gag reflex such as during oral cavity care.
** Diarrhoea will be defined as >5 liquid stools or an estimated stool volume of >1000 ml within a 24-hour period.
*** Constipation will be defined as failure to pass any stools for >3 consecutive full calendar days.
Timepoint [1] 297364 0
Time of discharge from ICU or 14 days after randomisation, whichever is earlier
Secondary outcome [1] 320819 0
Days free of gastrointestinal intolerance (a composite outcome of vomiting, diarrhoea or constipation; which would be assessed on review of medical records and with the help of a bedside vomiting and diarrhoea nursing observation chart). It would be calculated as a two step process:
1) Number of days when the patient had vomiting, diarrhea or constipation will be assessed during the first 14 study days after randomization. In regards to constipation, only those days that are beyond the three consecutive full calendar days without bowel motions will be counted.
2) The above number of days will be subtracted from total eligible study days for each patient to derive the number of days when the patient was alive and free of vomiting, diarrhoea or constipation.
Timepoint [1] 320819 0
Day 14 after randomisation
Secondary outcome [2] 320820 0
Episodes of vomiting or diarrhoea per patient (this is a composite outcome that would be assessed on review of medical records and with the help of a bedside vomiting and diarrhoea nursing observation chart)
Timepoint [2] 320820 0
Time of discharge from ICU or 14 days after randomisation, whichever is earlier
Secondary outcome [3] 320821 0
Time (in days) from randomisation to first episode of vomiting or diarrhoea (this is a composite outcome that would be assessed on review of medical records and with the help of a bedside vomiting and diarrhoea nursing observation chart)
Timepoint [3] 320821 0
Day 14 after randomisation
Secondary outcome [4] 320822 0
Mean diet volume ratio (diet received/ diet prescribed) expressed as percentage. This would be calculated as a three-step process based on the review of medical records and ICU observation charts:
1) A sum-total of target feed volume during all eligible study days will be determined for each patient.
2) Then the total enteral feed delivered (subtracting the discarded gastric aspirate volume) during those eligible study days will be determined for each patient.
3) The ration between the feed delivered (adjusted for discarded gastric aspirate) and the target feed volume will be expressed as a percentage for each patient.
Timepoint [4] 320822 0
Time of discharge from ICU or 14 days after randomisation, whichever is earlier
Secondary outcome [5] 320823 0
Ventilator-free days, as assessed by review of medical records and ICU observation charts
Timepoint [5] 320823 0
Time of discharge from ICU or 14 days after randomisation, whichever is earlier
Secondary outcome [6] 320824 0
All-cause mortality, as assessed by review of medical records
Timepoint [6] 320824 0
Time of hospital discharge

Eligibility
Key inclusion criteria
1) Patients who are receiving invasive mechanical ventilation (IMV) and are deemed likely to require IMV for at least the next 24 hours.
2) Age equal to or more than 18 years
3) Naso or Oro-gastric tube is in situ or its insertion is imminent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Patients with ICU stay of more than 72 hours after initiation of IMV
2) Moribund patients or those patients with an imminent risk of death within the next 48 hours.
3) Patients who are not deemed fit for enteral feeding by the treating team.
4) Patients with history of esophageal or gastric surgery within the last month.
5) Patients with gastric banding procedure
6) Patients with acute starvation (i.e., no nutrition for >5 days)
7) Patients who had intestinal resection with less than 200 cm of small intestine remaining.
8) Patients with known hiatus hernia.
9) Patients with feeding jejunostomy tubes in situ.
10) Patients receiving total parenteral nutrition.
11) Patients who suffer from cachexia or severely malnourished state
12) Patients with history of malabsorptive or gastrointestinal motility disorders (e.g. irritable bowel syndrome or inflammatory bowel diseases or diabetic gastroparesis)
13) Patients in whom semi-recumbent right lateral position is contraindicated or not feasible.
14) Treating clinician lacks equipoise or believes that bolus/ intermittent feeding is not in patient’s best interests

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)
Enrolled patients will be randomly allocated, using opaque sealed envelopes, to either standard care arm or intermittent postural feeding arm. The randomization method would be via permuted block randomization with variable block sizes stratified by site. Envelopes will not be opened until participants fulfill all eligibility criteria and are ready to be assigned to study treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Using a web-based computer program, a third party will generate a randomization list for each site. Randomization number and the allocated arm will be typewritten in a lighter font on a colored A4 page, which will be then folded and inserted in a sequentially numbered opaque envelope for each patient. It will be impossible to decipher the allocated arm by holding the envelope against a bright light. All envelopes will then be sealed and securely stored in a locked cabinet.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will be conducted on an intention-to-treat basis. Standard statistical software package will be used for analysis. All data will be assessed for normality and log-transformed where appropriate. Continuous normally distributed variables will be compared using Student’s t-tests and reported as means (standard deviation (SD)), whilst non-normally distributed data will be compared using Wilcoxon rank sum tests and reported as medians (interquartile range (IQR)). Categorical data will be compared using chi-square tests for equal proportions or Fisher’s exact tests (where numbers are small) and reported as n (%). Time-to-event (vomiting/ diarrhoea) data will be compared using Kaplan-Meier curves and log rank sum tests to determine statistical significance between the curves. Multivariate time-to-event analysis will be performed using Cox proportional hazards regression adjusted for a priori defined baseline variables (age, history of intra-abdominal surgery, IMV duration prior to randomisation, and liver SOFA score) and results will be reported as hazard ratios with 95% confidence intervals. Sensitivity analysis will be performed where constipation is defined as failure to pass any stools for >6 consecutive full calendar days.. A two-sided p-value of <0.05 will be considered to be statistically significant.

Sample size: In a previous RCT (n=30), the incidence of constipation or diarrhea during the three study days in the continuous versus intermittent enteral nutrition arm were 12/15 (80%) versus 8/15 (53%). Therefore, assuming an incidence rate of 80% for the primary outcome measure of gastrointestinal intolerance (vomiting, diarrhoea or constipation) in the control group, we would require a sample size of 60 patients per group to demonstrate a 30% absolute risk reduction in the intervention group (i.e., resulting in an incidence rate of 50% for gastrointestinal intolerance in the intervention group). This sample size would provide 90% power at a two-sided p value of <0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2016
Actual
Date of last participant enrolment
Anticipated
31/07/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC
Recruitment hospital [1] 5274 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [2] 5275 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 5276 0
Frankston Hospital - Frankston
Recruitment hospital [4] 5277 0
The Canberra Hospital - Garran
Recruitment hospital [5] 5278 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [6] 5279 0
Newcastle Private Hospital - New Lambton Heights
Recruitment postcode(s) [1] 12736 0
2300 - Newcastle
Recruitment postcode(s) [2] 12738 0
3199 - Frankston
Recruitment postcode(s) [3] 12739 0
2605 - Garran
Recruitment postcode(s) [4] 12740 0
2340 - East Tamworth
Recruitment postcode(s) [5] 12741 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 12742 0
2298 - Waratah

Funding & Sponsors
Funding source category [1] 292891 0
Charities/Societies/Foundations
Name [1] 292891 0
John Hunter Charitable Trust
Country [1] 292891 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
ICU, John Hunter Hospital,
Lookout road, New Lambton, NSW 2305
Country
Australia
Secondary sponsor category [1] 291634 0
None
Name [1] 291634 0
Address [1] 291634 0
Country [1] 291634 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294392 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 294392 0
Ethics committee country [1] 294392 0
Australia
Date submitted for ethics approval [1] 294392 0
26/11/2015
Approval date [1] 294392 0
02/02/2016
Ethics approval number [1] 294392 0
HNEHREC Reference No: 15/12/16/4.04

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

Contacts
Principal investigator
Name 45162 0
Dr Rakshit Panwar
Address 45162 0
ICU, John Hunter Hospital Locked Bag 1, Hunter Regional Mail Centre, NSW, 2310
Country 45162 0
Australia
Phone 45162 0
+61410218808
Fax 45162 0
Email 45162 0
rakshit.panwar@hnehealth.nsw.gov.au
Contact person for public queries
Name 45163 0
Rakshit Panwar
Address 45163 0
ICU, John Hunter Hospital Locked Bag 1, Hunter Regional Mail Centre, NSW, 2310
Country 45163 0
Australia
Phone 45163 0
+61410218808
Fax 45163 0
Email 45163 0
rakshit.panwar@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 45164 0
Rakshit Panwar
Address 45164 0
ICU, John Hunter Hospital Locked Bag 1, Hunter Regional Mail Centre, NSW, 2310
Country 45164 0
Australia
Phone 45164 0
+61410218808
Fax 45164 0
Email 45164 0
rakshit.panwar@hnehealth.nsw.gov.au

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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