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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 44
- 主要终点
- Average Daily Protein Adequacy Over the First 5 Days of Treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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]).
研究组 & 干预措施
Group A: TAK-954 0.1 mg
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.
干预措施: TAK-954 (Drug)
Group A: TAK-954 0.1 mg
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.
干预措施: Normal Saline (Drug)
Group B: TAK-954 0.3 mg
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.
干预措施: TAK-954 (Drug)
Group B: TAK-954 0.3 mg
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.
干预措施: Normal Saline (Drug)
Group C: TAK-954 1.0 mg
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.
干预措施: TAK-954 (Drug)
Group C: TAK-954 1.0 mg
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.
干预措施: Normal Saline (Drug)
Group D: Metoclopramide 10 mg
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.
干预措施: Metoclopramide (Drug)
Group D: Metoclopramide 10 mg
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.
干预措施: Normal Saline (Drug)
结局指标
主要结局
Average Daily Protein Adequacy Over the First 5 Days of Treatment
时间窗: 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.
次要结局
- 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)
- 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 Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment(Days 1 to 5)
- Average Daily Caloric Adequacy(Days 1 to 5 and Days 1 to 14)
- Time to Resolution of Enteral Feeding Intolerance (EFI)(Days 1 to 14 or until resolution of EFI, whichever occurs first)