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

Critical Illness Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03477903
• Other study ID #: TAK-954-2002
• Secondary ID: U1111-1208-18312
• Status: Terminated
• Phase: Phase 2
• Start date: August 25, 2018
• Est. completion date: August 29, 2018

Study information

• Verified date: September 2019
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: August 29, 2018
• Est. primary completion date: August 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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]).

Related Conditions & MeSH terms

• Critical Illness
• Enteral Feeding Intolerance
• Enteral Nutrition

Intervention

Drug:
• TAK-954
TAK-954 infusion
• Metoclopramide
Metoclopramide infusion
• Normal Saline
0.9% sodium chloride for injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Days 1 to 5
Secondary	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.	Days 1 to 14
Secondary	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.	Days 1 to 5
Secondary	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.	Days 1 to 5 and Days 1 to 14
Secondary	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.	Days 1 to 14 or until resolution of EFI, whichever occurs first
Secondary	Percentage of Participants Achieving at Least 80% of Daily Goal Calories		Days 1 to 14 or end of treatment
Secondary	Percentage of Participants Achieving at Least 80% of Daily Goal Protein		Days 1 to 14 or end of treatment
Secondary	Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954		Day 5 pre-dose