Back to resultsTAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)
Primary Purpose
Critical Illness, Enteral Nutrition, Enteral Feeding Intolerance
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TAK-954
Metoclopramide
Normal Saline
Sponsored by
About this trial
This is an interventional treatment trial for Critical Illness focused on measuring Drug therapy
Eligibility Criteria
Inclusion Criteria:
- Has at least a size 12-(french size) Fr nasogastric or orogastric tube with its tip at least 10 centimeter (cm) below the esophagogastric junction confirmed radiologically (the tip of the tube must be in the body or the antrum of the stomach and not in the fundus).
- Is intubated and mechanically ventilated in the ICU.
- Is expected to remain alive, mechanically ventilated, and receive continuous enteral feeding for >=48 hours following randomization.
- Have EFI, defined as a single GRV measurement of >=250 mL with vomiting/retching within the last 24 hours, or a single GRV measurement of >=500 mL with or without vomiting/retching within the last 24 hours.
Exclusion Criteria:
- Is under consideration for withdrawal of life-sustaining treatments within the next 72 hours.
- Has had major esophageal or gastric surgery or direct luminal trauma on this admission (participants with lower abdominal surgery are not excluded unless enteral feeding is contraindicated).
- Has mechanical bowel obstruction, short bowel syndrome, or the presence of an active gastric pacemaker.
- Have pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
- Has been admitted primarily for treatment of a drug overdose.
- Has a presence of a post-pyloric tube in place at Randomization that may be used for enteral nutrition.
- Is receiving parenteral nutrition (PN) at Screening.
- Is in diabetic ketoacidosis or non-ketotic hyperosmolar coma.
- Has a different nutrient requirement than allowed in feeding protocol.(outside a range of 1.2 to 2 gram per kilogram per day [g/kg/day] of proteins and up to 1.5 kilocalorie per milliliter [kcal/mL]).
Sites / Locations
- Joseph M Still Burn Centers
- Eastern Idaho Medical Consultants
- Illinois Lung & Critical Care Institute
- University of Kentucky Health Care
- Anne Arundel Medical Center
- Truman Medical Center Hospital Hill
- Creighton University
- Englewood Hospital and Medical Center
- New York-Presbyterian Columbia University Medical Center
- Duke University Medical Center
- Cleveland Clinic
- University of Oklahoma Health Sciences Center
- The University of Texas Health Science Center at Houston
- Froedtert Hospital
- Royal North Shore Hospital
- Royal Brisbane and Women's Hospital
- Logan Hospital
- Mater Hospital Brisbane
- Royal Adelaide Hospital
- Flinders Medical Centre
- Monash Medical Centre
- The Northern Hospital
- Frankston Hospital
- The Royal Melbourne Hospital
- Royal Columbian Hospital
- St. Paul's Hospital
- Kingston General Hospital
- Hopital Charles-LeMoyne
- Hopital du Sacre-Coeur de Montreal
- McGill University Health Centre
- Centre Hospitalier Universitaire de Quebec Hospital Centre Hospitalier de IUniversite Laval
- University Hospitals Birmingham NHS Foundation Trust
- Royal Sussex County Hospital
- University Hospitals Bristol NHS Foundation Trust
- The Leeds Teaching Hospitals NHS Trust
- The Royal London Hospital
- Royal Free London NHS Foundation Trust
- Guy's and Saint Thomas' NHS Foundation Trust
- King's College Hospital NHS Foundation Trust
- NHS Lothian
- NHS Greater Glasgow and Clyde
- Cardiff and Vale University Health Board
- Aneurin Bevan University Health Board
- Royal Liverpool University Hospital NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Group A: TAK-954 0.1 mg
Group B: TAK-954 0.3 mg
Group C: TAK-954 1.0 mg
Group D: Metoclopramide 10 mg
Arm Description
TAK-954 0.1 milligram (mg), intravenously, administered as 60 minute-infusion, once daily along with 2 milliliter (mL) normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
TAK-954 0.3 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
TAK-954 1.0 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
Metoclopramide 10 mg, injection, intravenously, three times a day along with 100 mL normal saline 60-minute infusion, intravenously, once daily for a minimum of 5 days up to a maximum of 14 days.
Outcomes
Primary Outcome Measures
Average Daily Protein Adequacy Over the First 5 Days of Treatment
Average daily protein adequacy received through enteral nutrition is defined as the percentage of goal protein delivered per day, where percentage of goal protein delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 5 days was averaged.
Secondary Outcome Measures
Average Daily Protein Adequacy Over the Study Treatment Period
Average daily protein adequacy received through enteral nutrition is defined as percentage of goal protein delivered per day, where percentage of protein goal delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 14 days was averaged.
Average Daily Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment
GRV is defined as the volume of fluid remaining in the stomach at a point in time during enteral nutrition feeding. The value for each of the 5 days was averaged.
Average Daily Caloric Adequacy
Average daily caloric adequacy received through enteral nutrition was defined by percentage of goal calories achieved per day (percentage calorie goal achieved=actual calorie achievement/total participant-specific target calories). The values in the 5-day period and the 14-day period were averaged.
Time to Resolution of Enteral Feeding Intolerance (EFI)
Time to resolution of EFI is defined as the time needed to achieve GRV less than or equal to 250 ml in the absence of vomiting/retching.
Percentage of Participants Achieving at Least 80% of Daily Goal Calories
Percentage of Participants Achieving at Least 80% of Daily Goal Protein
Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954
Full Information
NCT ID
NCT03477903
First Posted
March 19, 2018
Last Updated
September 23, 2019
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03477903
Brief Title
TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)
Official Title
A Phase 2b, Randomized, Multi-Center, Double-Blind, Dose-Ranging Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous TAK-954 in Critically Ill Patients With Enteral Feeding Intolerance
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Insufficient enrollment; No safety concerns
Study Start Date
August 25, 2018 (Actual)
Primary Completion Date
August 29, 2018 (Actual)
Study Completion Date
August 29, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the treatment effect of intravenous TAK-954 in improving the average daily protein adequacy received through enteral nutrition in critically-ill participants developing EFI.
Detailed Description
The drug being tested in this study is called TAK-954. The study will assess the treatment effect of intravenous TAK-954 in improving average daily protein adequacy received through enteral nutrition in critically ill participants with EFI.
The study will enroll approximately 200 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 4 treatment groups -which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
Group A: TAK-954 0.1 mg
Group B: TAK-954 0.3 mg
Group C: TAK-954 1 mg
Group D: Metoclopramide 10 mg
This multi-center trial will be conducted in the United States, United Kingdom, Australia and Canada. The overall duration of treatment in this study is maximum of 14 days while in hospital. Participants will be contacted by telephone 30 and 90 days after receiving their last dose of study drug for a follow-up assessment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Enteral Nutrition, Enteral Feeding Intolerance
Keywords
Drug therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: TAK-954 0.1 mg
Arm Type
Experimental
Arm Description
TAK-954 0.1 milligram (mg), intravenously, administered as 60 minute-infusion, once daily along with 2 milliliter (mL) normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
Arm Title
Group B: TAK-954 0.3 mg
Arm Type
Experimental
Arm Description
TAK-954 0.3 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
Arm Title
Group C: TAK-954 1.0 mg
Arm Type
Experimental
Arm Description
TAK-954 1.0 mg, intravenously, administered as 60 minute-infusion, once daily along with 2 mL normal saline injection, intravenously, three times a day for a minimum of 5 days up to a maximum of 14 days.
Arm Title
Group D: Metoclopramide 10 mg
Arm Type
Active Comparator
Arm Description
Metoclopramide 10 mg, injection, intravenously, three times a day along with 100 mL normal saline 60-minute infusion, intravenously, once daily for a minimum of 5 days up to a maximum of 14 days.
Intervention Type
Drug
Intervention Name(s)
TAK-954
Intervention Description
TAK-954 infusion
Intervention Type
Drug
Intervention Name(s)
Metoclopramide
Intervention Description
Metoclopramide infusion
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
0.9% sodium chloride for injection
Primary Outcome Measure Information:
Title
Average Daily Protein Adequacy Over the First 5 Days of Treatment
Description
Average daily protein adequacy received through enteral nutrition is defined as the percentage of goal protein delivered per day, where percentage of goal protein delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 5 days was averaged.
Time Frame
Days 1 to 5
Secondary Outcome Measure Information:
Title
Average Daily Protein Adequacy Over the Study Treatment Period
Description
Average daily protein adequacy received through enteral nutrition is defined as percentage of goal protein delivered per day, where percentage of protein goal delivered is calculated as the ratio of actual protein achievement to the total participant-specific target protein prescribed. The value for each of the 14 days was averaged.
Time Frame
Days 1 to 14
Title
Average Daily Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment
Description
GRV is defined as the volume of fluid remaining in the stomach at a point in time during enteral nutrition feeding. The value for each of the 5 days was averaged.
Time Frame
Days 1 to 5
Title
Average Daily Caloric Adequacy
Description
Average daily caloric adequacy received through enteral nutrition was defined by percentage of goal calories achieved per day (percentage calorie goal achieved=actual calorie achievement/total participant-specific target calories). The values in the 5-day period and the 14-day period were averaged.
Time Frame
Days 1 to 5 and Days 1 to 14
Title
Time to Resolution of Enteral Feeding Intolerance (EFI)
Description
Time to resolution of EFI is defined as the time needed to achieve GRV less than or equal to 250 ml in the absence of vomiting/retching.
Time Frame
Days 1 to 14 or until resolution of EFI, whichever occurs first
Title
Percentage of Participants Achieving at Least 80% of Daily Goal Calories
Time Frame
Days 1 to 14 or end of treatment
Title
Percentage of Participants Achieving at Least 80% of Daily Goal Protein
Time Frame
Days 1 to 14 or end of treatment
Title
Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954
Time Frame
Day 5 pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has at least a size 12-(french size) Fr nasogastric or orogastric tube with its tip at least 10 centimeter (cm) below the esophagogastric junction confirmed radiologically (the tip of the tube must be in the body or the antrum of the stomach and not in the fundus).
Is intubated and mechanically ventilated in the ICU.
Is expected to remain alive, mechanically ventilated, and receive continuous enteral feeding for >=48 hours following randomization.
Have EFI, defined as a single GRV measurement of >=250 mL with vomiting/retching within the last 24 hours, or a single GRV measurement of >=500 mL with or without vomiting/retching within the last 24 hours.
Exclusion Criteria:
Is under consideration for withdrawal of life-sustaining treatments within the next 72 hours.
Has had major esophageal or gastric surgery or direct luminal trauma on this admission (participants with lower abdominal surgery are not excluded unless enteral feeding is contraindicated).
Has mechanical bowel obstruction, short bowel syndrome, or the presence of an active gastric pacemaker.
Have pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
Has been admitted primarily for treatment of a drug overdose.
Has a presence of a post-pyloric tube in place at Randomization that may be used for enteral nutrition.
Is receiving parenteral nutrition (PN) at Screening.
Is in diabetic ketoacidosis or non-ketotic hyperosmolar coma.
Has a different nutrient requirement than allowed in feeding protocol.(outside a range of 1.2 to 2 gram per kilogram per day [g/kg/day] of proteins and up to 1.5 kilocalorie per milliliter [kcal/mL]).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Joseph M Still Burn Centers
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
Eastern Idaho Medical Consultants
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Illinois Lung & Critical Care Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
University of Kentucky Health Care
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Anne Arundel Medical Center
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Truman Medical Center Hospital Hill
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Creighton University
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Englewood Hospital and Medical Center
City
Englewood
State/Province
New Jersey
ZIP/Postal Code
07631
Country
United States
Facility Name
New York-Presbyterian Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Froedtert Hospital
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal North Shore Hospital
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Logan Hospital
City
Meadowbrook
State/Province
Queensland
ZIP/Postal Code
4131
Country
Australia
Facility Name
Mater Hospital Brisbane
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
The Northern Hospital
City
Epping
State/Province
Victoria
ZIP/Postal Code
3076
Country
Australia
Facility Name
Frankston Hospital
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
The Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Royal Columbian Hospital
City
New Westminster
State/Province
British Columbia
ZIP/Postal Code
V3L 3W4
Country
Canada
Facility Name
St. Paul's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Hopital Charles-LeMoyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Hopital du Sacre-Coeur de Montreal
City
Monteal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Quebec Hospital Centre Hospitalier de IUniversite Laval
City
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
Royal Sussex County Hospital
City
Brighton
State/Province
England
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
University Hospitals Bristol NHS Foundation Trust
City
Bristol
State/Province
England
ZIP/Postal Code
BS2 8HW
Country
United Kingdom
Facility Name
The Leeds Teaching Hospitals NHS Trust
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
The Royal London Hospital
City
London
State/Province
England
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Royal Free London NHS Foundation Trust
City
London
State/Province
England
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Guy's and Saint Thomas' NHS Foundation Trust
City
London
State/Province
England
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust
City
London
State/Province
England
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
NHS Lothian
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH16 4SB
Country
United Kingdom
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G42 9TY
Country
United Kingdom
Facility Name
Cardiff and Vale University Health Board
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XN
Country
United Kingdom
Facility Name
Aneurin Bevan University Health Board
City
Newport
State/Province
Wales
ZIP/Postal Code
NP20 2UB
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital NHS Trust
City
Liverpool
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Learn more about this trial
TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)
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