TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)

Phase 2

Terminated

Conditions: Enteral Nutrition
Enteral Feeding Intolerance
Critical Illness

Interventions: Drug: TAK-954
Drug: Metoclopramide
Drug: Normal Saline

Registration Number: NCT03477903

Lead Sponsor: Millennium Pharmaceuticals, Inc.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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]).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B: TAK-954 0.3 mg	TAK-954	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.
Group B: TAK-954 0.3 mg	Normal Saline	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.
Group C: TAK-954 1.0 mg	Normal Saline	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.
Group D: Metoclopramide 10 mg	Normal Saline	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.
Group A: TAK-954 0.1 mg	TAK-954	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.
Group A: TAK-954 0.1 mg	Normal Saline	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.
Group C: TAK-954 1.0 mg	TAK-954	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.
Group D: Metoclopramide 10 mg	Metoclopramide	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.

Primary Outcome Measures

Name	Time	Method
Average Daily Protein Adequacy Over the First 5 Days of Treatment	Days 1 to 5	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

Name	Time	Method
Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954	Day 5 pre-dose
Percentage of Participants Achieving at Least 80% of Daily Goal Protein	Days 1 to 14 or end of treatment
Time to Resolution of Enteral Feeding Intolerance (EFI)	Days 1 to 14 or until resolution of EFI, whichever occurs first	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	Days 1 to 14 or end of treatment
Average Daily Protein Adequacy Over the Study Treatment Period	Days 1 to 14	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	Days 1 to 5	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	Days 1 to 5 and Days 1 to 14	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.

Trial Locations

Locations (44): St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Cardiff and Vale University Health Board
🇬🇧
Cardiff, Wales, United Kingdom
Royal Columbian Hospital
🇨🇦
New Westminster, British Columbia, Canada
Joseph M Still Burn Centers
🇺🇸
Augusta, Georgia, United States
Eastern Idaho Medical Consultants
🇺🇸
Idaho Falls, Idaho, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
The University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
Anne Arundel Medical Center
🇺🇸
Annapolis, Maryland, United States
Illinois Lung & Critical Care Institute
🇺🇸
Peoria, Illinois, United States
Truman Medical Center Hospital Hill
🇺🇸
Kansas City, Missouri, United States
Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
Hopital Charles-LeMoyne
🇨🇦
Greenfield Park, Quebec, Canada
Hopital du Sacre-Coeur de Montreal
🇨🇦
Monteal, Quebec, Canada
Royal North Shore Hospital
🇦🇺
St. Leonards, New South Wales, Australia
Royal Sussex County Hospital
🇬🇧
Brighton, England, United Kingdom
Centre Hospitalier Universitaire de Quebec Hospital Centre Hospitalier de IUniversite Laval
🇨🇦
Quebec, Canada
Guy's and Saint Thomas' NHS Foundation Trust
🇬🇧
London, England, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧
Birmingham, England, United Kingdom
Royal Liverpool University Hospital NHS Trust
🇬🇧
Liverpool, United Kingdom
The Royal London Hospital
🇬🇧
London, England, United Kingdom
The Leeds Teaching Hospitals NHS Trust
🇬🇧
Leeds, England, United Kingdom
NHS Lothian
🇬🇧
Edinburgh, Scotland, United Kingdom
University of Kentucky Health Care
🇺🇸
Lexington, Kentucky, United States
Creighton University
🇺🇸
Omaha, Nebraska, United States
Englewood Hospital and Medical Center
🇺🇸
Englewood, New Jersey, United States
New York-Presbyterian Columbia University Medical Center
🇺🇸
New York, New York, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Froedtert Hospital
🇺🇸
Wauwatosa, Wisconsin, United States
Royal Brisbane and Women's Hospital
🇦🇺
Brisbane, Queensland, Australia
Logan Hospital
🇦🇺
Meadowbrook, Queensland, Australia
Mater Hospital Brisbane
🇦🇺
South Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
The Northern Hospital
🇦🇺
Epping, Victoria, Australia
Frankston Hospital
🇦🇺
Frankston, Victoria, Australia
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
McGill University Health Centre
🇨🇦
Montreal, Quebec, Canada
The Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
University Hospitals Bristol NHS Foundation Trust
🇬🇧
Bristol, England, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧
London, England, United Kingdom
NHS Greater Glasgow and Clyde
🇬🇧
Glasgow, Scotland, United Kingdom
Aneurin Bevan University Health Board
🇬🇧
Newport, Wales, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧
London, England, United Kingdom