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

Millennium Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Enteral Nutrition; Critical Illness; Enteral Feeding Intolerance

Treatments: Drug: Metoclopramide; Drug: Normal Saline; Drug: TAK-954

Study type: Interventional

Funder types: Industry

Identifiers

NCT03477903

18/NE/0139 (Registry Identifier)

TAK-954-2002

2017-003206-41 (EudraCT Number)

U1111-1208-1831 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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]).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1 participants in 4 patient groups

Group A: TAK-954 0.1 mg

Experimental group

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.

Treatment:

Drug: TAK-954

Drug: Normal Saline

Group B: TAK-954 0.3 mg

Experimental group

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.

Treatment:

Drug: TAK-954

Drug: Normal Saline

Group C: TAK-954 1.0 mg

Experimental group

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.

Treatment:

Drug: TAK-954

Drug: Normal Saline

Group D: Metoclopramide 10 mg

Active Comparator group

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.

Treatment:

Drug: Normal Saline

Drug: Metoclopramide