Clinical trial NCT03477903: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Critical Illness
Enteral Nutrition
Enteral Feeding Intolerance
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-03-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Is intubated and mechanically ventilated in the ICU.
3. Is expected to remain alive, mechanically ventilated, and receive continuous enteral feeding for \>=48 hours following randomization.
4. 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:

1. Is under consideration for withdrawal of life-sustaining treatments within the next 72 hours.
2. 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).
3. Has mechanical bowel obstruction, short bowel syndrome, or the presence of an active gastric pacemaker.
4. 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).
5. Has been admitted primarily for treatment of a drug overdose.
6. Has a presence of a post-pyloric tube in place at Randomization that may be used for enteral nutrition.
7. Is receiving parenteral nutrition (PN) at Screening.
8. Is in diabetic ketoacidosis or non-ketotic hyperosmolar coma.
9. 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 \[kcal/mL\]).

Primary outcomes:
measure: Average Daily Protein Adequacy Over the First 5 Days of Treatment
timeFrame: Days 1 to 5
Secondary outcomes:
measure: Average Daily Protein Adequacy Over the Study Treatment Period
timeFrame: Days 1 to 14
measure: Average Daily Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment
timeFrame: Days 1 to 5
measure: Average Daily Caloric Adequacy
timeFrame: Days 1 to 5 and Days 1 to 14
measure: Time to Resolution of Enteral Feeding Intolerance (EFI)
timeFrame: Days 1 to 14 or until resolution of EFI, whichever occurs first
measure: Percentage of Participants Achieving at Least 80% of Daily Goal Calories
timeFrame: Days 1 to 14 or end of treatment
measure: Percentage of Participants Achieving at Least 80% of Daily Goal Protein
timeFrame: Days 1 to 14 or end of treatment
measure: Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954
timeFrame: Day 5 pre-dose
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Joseph M Still Burn Centers
state: Georgia
city: Idaho Falls
country: United States
facility: Eastern Idaho Medical Consultants
state: Idaho
city: Peoria
country: United States
facility: Illinois Lung & Critical Care Institute
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Health Care
state: Kentucky
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Kansas City
country: United States
facility: Truman Medical Center Hospital Hill
state: Missouri
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: New York
country: United States
facility: New York-Presbyterian Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Wauwatosa
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Meadowbrook
country: Australia
facility: Logan Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Epping
country: Australia
facility: The Northern Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles-LeMoyne
state: Quebec
city: Monteal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec Hospital Centre Hospitalier de IUniversite Laval
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: England
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
state: England
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust
state: England
city: London
country: United Kingdom
facility: The Royal London Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
state: Scotland
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
state: Scotland
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
state: Wales
city: Newport
country: United Kingdom
facility: Aneurin Bevan University Health Board
state: Wales
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital NHS Trust
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: