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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01934192




Registration number
NCT01934192
Ethics application status
Date submitted
29/08/2013
Date registered
4/09/2013
Date last updated
11/12/2017

Titles & IDs
Public title
Nutritional Adequacy Therapeutic Enhancement in the Critically Ill. The NUTRIATE Study
Scientific title
NUTRItional Adequacy Therapeutic Enhancement in the Critically Ill: A Randomized Double Blind, Placebo-controlled Trial of the Motilin Receptor Agonist GSK962040. The NUTRIATE Study
Secondary ID [1] 0 0
113445
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastroparesis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK962040 50 mg
Treatment: Drugs - Metoclopramide 10 mg
Treatment: Drugs - Placebo NG
Treatment: Drugs - Placebo IV

Experimental: Initial randomization: GSK962040 Arm - Subjects in the GSK962040 Arm will receive 50 mg once daily enteral dose administered through NG tube up to 7 days.

Placebo comparator: Initial randomization: Placebo Arm - Subjects in the placebo arm will receive once daily dose enteral dose administered through NG tube up to 7 days.

Experimental: Treatment change due to intolerance: GSK962040 Arm - Subjects that develop intolerance and that originally received Placebo will receive 50 mg once daily enteral dose administered through NG tube + placebo IV

Active comparator: Treatment change due to intolerance: Metoclopramide Arm - Subjects that develop intolerance and that originally received GSK962040 will receive metoclopramide 10 mg IV every 6 h + placebo NG


Treatment: Drugs: GSK962040 50 mg
GSK962040 50 mg will be administered once daily enteral dose through NG tube up to 7 days.

Treatment: Drugs: Metoclopramide 10 mg
Metoclopramide will be administered IV every 6 h

Treatment: Drugs: Placebo NG
Matching placebo once daily enteral dose will be administered through NG tube up to 7 days

Treatment: Drugs: Placebo IV
Placebo will be administered IV every 6 hours
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average Percentage Goal Volume Delivered Prior to Development of Intolerance for ITT Population
Timepoint [1] 0 0
Up to Day 7
Primary outcome [2] 0 0
Average Percentage Goal Volume Delivered Prior to Development of Intolerance for PP Population
Timepoint [2] 0 0
Up to Day 7
Secondary outcome [1] 0 0
Average Percentage Goal Calories Delivered Prior to Development of Intolerance
Timepoint [1] 0 0
Up to Day 7
Secondary outcome [2] 0 0
Average Percentage Goal Protein Delivered Prior to Development of Intolerance
Timepoint [2] 0 0
Up to Day 7
Secondary outcome [3] 0 0
Time to Delivery of 80 Percent Prescribed Calories Prior to Intolerance
Timepoint [3] 0 0
Up to Day 7
Secondary outcome [4] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [4] 0 0
up to 23 days
Secondary outcome [5] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [5] 0 0
Up to 23 days
Secondary outcome [6] 0 0
Change From Baseline in Heart Rate (HR)
Timepoint [6] 0 0
Up to 23 days
Secondary outcome [7] 0 0
Number of Participants With Maximum Increase From Baseline in Electrocardiogram (ECG) Values
Timepoint [7] 0 0
Up to 23 days
Secondary outcome [8] 0 0
Change From Baseline in Albumin and Total Protein Levels
Timepoint [8] 0 0
Up to 23 days
Secondary outcome [9] 0 0
Change From Baseline in Alkaline Phosphatase (Alk. Phosph.), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Levels
Timepoint [9] 0 0
Up to 23 days
Secondary outcome [10] 0 0
Change From Baseline in Total and Direct Bilirubin, Creatinine and Uric Acid Levels
Timepoint [10] 0 0
Up to 23 days
Secondary outcome [11] 0 0
Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, Blood Urea Nitrogen (BUN) Values
Timepoint [11] 0 0
Up to 23 days
Secondary outcome [12] 0 0
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Levels
Timepoint [12] 0 0
Up to 23 days
Secondary outcome [13] 0 0
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Levels
Timepoint [13] 0 0
Up to 23 days
Secondary outcome [14] 0 0
Change From Baseline in Hematocrit Level
Timepoint [14] 0 0
Up to 23 days
Secondary outcome [15] 0 0
Change From Baseline in Mean Corpuscle Volume (MCV) Levels
Timepoint [15] 0 0
Up to 23 days
Secondary outcome [16] 0 0
Change From Baseline in Red Blood Cell (RBC) and Reticulocyte Count
Timepoint [16] 0 0
Up to 23 days
Secondary outcome [17] 0 0
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Levels
Timepoint [17] 0 0
Up to 23 days
Secondary outcome [18] 0 0
Log Transformed Concentration at 60 Minutes (Min) (C60) and Maximum Observed Concentration (Cmax) of Acetaminophen (Prior to Intolerance)
Timepoint [18] 0 0
At Day 2
Secondary outcome [19] 0 0
Log Transformed AUC[0-60] of Acetaminophen
Timepoint [19] 0 0
At Day 2
Secondary outcome [20] 0 0
Log Transformed AUC[0-60] of 3-O-methylglucose (3- OMG)
Timepoint [20] 0 0
At Day 2
Secondary outcome [21] 0 0
Log Transformed C60 of 3-OMG
Timepoint [21] 0 0
At Day 2
Secondary outcome [22] 0 0
Derived Tmax of 3-OMG Post Intolerance
Timepoint [22] 0 0
At Day 2
Secondary outcome [23] 0 0
Percentage of Participants That Became Intolerant
Timepoint [23] 0 0
Up to Day 7
Secondary outcome [24] 0 0
Time to Development of Feeding Intolerance
Timepoint [24] 0 0
Up to Day 7
Secondary outcome [25] 0 0
GE Assessment as AUC (0-60) Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using Acetaminophen
Timepoint [25] 0 0
Day 2
Secondary outcome [26] 0 0
GE Assessment as Cmax Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using Acetaminophen
Timepoint [26] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [27] 0 0
GE Assessment as AUC (0-60) and AUC (0-240) Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using 3-OMG
Timepoint [27] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [28] 0 0
GE Assessment as C60 Within 24 Hrs of Developing Intolerance and Prior to Change of Treatment Using 3-OMG
Timepoint [28] 0 0
Baseline, Day 2, Day 3, Day 4
Secondary outcome [29] 0 0
Number of Participants With Occurrences of Vomiting, Regurgitation and Macroaspiration Episodes
Timepoint [29] 0 0
up to 23 days
Secondary outcome [30] 0 0
Total GRV for 24 hr Period
Timepoint [30] 0 0
Up to Day 7
Secondary outcome [31] 0 0
Log Transformed Derived Plasma Cmax of GSK962040 Prior to Intolerance
Timepoint [31] 0 0
Day 2, Day 3, Day 4, Day 7
Secondary outcome [32] 0 0
Log Transformed Derived Plasma Cmax of GSK962040 Post Intolerance
Timepoint [32] 0 0
Day 2 and Day 4
Secondary outcome [33] 0 0
Derived Tmax of GSK962040 Post Intolerance
Timepoint [33] 0 0
Day 2 and Day 4
Secondary outcome [34] 0 0
Derived AUC Over the Dosing Period [AUC(0-tau)] of GSK962040 Post Intolerance
Timepoint [34] 0 0
Day 2 and Day 4
Secondary outcome [35] 0 0
Derived Accumulation Ratio (RO) of GSK962040 Post Intolerance
Timepoint [35] 0 0
Baseline, Day 2, Day 3, Day 4

Eligibility
Key inclusion criteria
* Age & Gender: Male or female between 18 and 85 years of age inclusive, at the time of obtaining the informed consent.
* First admitted to participating ICU within the previous 48 hours.
* Intubated and invasively mechanically ventilated
* Indicated to receive early EN or are already receiving EN (subject must be on EN prior to receiving study treatment)
* Have at least one of the following
* Clinical evidence of cardiovascular dysfunction defined as the need for vasopressor agents (e.g. norepinephrine, epinephrine, vasopressin), >5 microgram/kg/min of dopamine, or >/= 50 microgram/min phenylephrine) for greater than or equal to 2 hours;
* Poly-trauma with an injury severity score (ISS) >=15 points
* Acute traumatic or non-traumatic brain injury Glasgow Coma Scale (GCS) <=12, prior to the initiation of sedation.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects who are not expected to be in the ICU and alive for at least 48 hrs from point of screening.
* Subjects with acute hepatitis (e.g. acute hepatitis B or C) or severe chronic liver disease (e.g. Child Pugh class C cirrhosis) will be excluded
* Liver function tests: If Alanine aminotransferase (ALT) >=8x upper limit of normal (ULN); OR If ALT >5-8x ULN and bilirubin >2<=3 ULN or bilirubin >3x ULN (Include only if bilirubin <1.5xULN); OR If ALT <=5xULN and Bilirubin >3xULN (Include only if ALT <=3xULN and Bilirubin >2 <=3xULN)
* Subjects who have received a gastric prokinetic agent in the previous 12 hours (e.g., erythromycin, azithromycin, metoclopramide, domperidone).
* QT duration corrected for heart rate (QTc) >480 ms. QTcF is the recommended correction factor for all sites. If QT duration corrected for heart rate by Fridericia's formula (QTcF) is not possible to obtain or calculate, QT duration corrected for heart rate by Bazett's formula (QTcB) or machine or manual over read, may be obtained after consultation with the medical monitor. The QT correction formula used to determine inclusion and discontinuation should be the same throughout the study.
* Use of strong Cyp3A4 inhibitors
* Subjects who require renal replacement therapy or with an estimated glomerular filtration rate (GFR) of <30 mL/min byCockroft-Gault calculation).
* Subjects who have a history of or who have undergone major esophageal or gastric surgery on this admission (major lower abdominal surgery will not result in exclusion unless this carries a contraindication to enteral feeding).
* Subjects with an absolute contraindication to enteral nutrition e.g. subjects with ongoing bowel obstruction or perforation.
* Subject has a gastric pacemaker
* Pregnant or lactating females
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
* Concurrent enrollment in other interventional study involving a novel (i.e.unapproved or experimental) chemical or biopharmaceutical entity.
* Previous randomization in this study
* Subjects for whom the reason for admission to ICU was an overdose (deliberate or accidental; medicinal product or not).
* Exclusion to re-randomization:
* Subjects with an untreated pheochromocytoma.
* Subjects with a past history of a seizure disorder (e.g., epilepsy) and is currently receiving anti-epileptic treatment for their seizure disorder, ongoing refractory, or sustained seizure disorder (prophylactic use for head injury/isolated new seizure maintained on anti-seizure meds in ICU acceptable).
* Subjects taking drugs likely to cause extrapyramidal reactions.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/04/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/07/2016
Sample size
Target
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Southport
Recruitment hospital [3] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [4] 0 0
GSK Investigational Site - Woodville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, parallel group, placebo-controlled and active-compared, randomized study to assess the ability of GSK962040 to enhance the delivery of enteral feed to critically ill subjects that are predisposed to developing feeding intolerance (e.g., percentage of goal volume); enhance gastric emptying in this population; and provide preliminary evidence of the drug's effect on outcomes of therapy (length of stay in the Intensive Care Unit \[ICU\], time on ventilator, ICU acquired infections, and 60-day mortality). Other aims are evaluation of GSK962040 safety, tolerability and pharmacokinetics upon repeat dosing in a critically ill population.

After meeting eligibility criteria, male and female subjects will be randomized to either receive GSK962040 (50 milligram \[mg\]) once daily (OD) via naso-gastric (NG) or orogastric (OG) feeding tube (oral solution), or placebo by the same route. If subjects develop intolerance to enteral feeding at any point up to Dose 5 of study medication (inclusive), study treatments will switch such that those originally receiving GSK962040 will receive metoclopramide (10 mg, intravenous \[iv\], every 6 hours) and those subjects originally randomized to receive placebo will receive GSK962040 (50 mg, via NG, OD). Additionally, if subjects develop intolerance prior to any treatment, they will be randomized to receive either GSK962040 (50 mg, via NG, OD) or metoclopramide (10 mg, iv, every 6 hours).

The study will consist of a screening/baseline assessment, a treatment period (up to 7 days in duration), and a 4-day post treatment safety follow-up assessment. The duration of each subject's participation in the study from screening to follow-up safety assessment will be up to approximately 2 weeks. In addition, mortality will be assessed 60 days after admission to the ICU.
Trial website
https://clinicaltrials.gov/study/NCT01934192
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01934192