Critical IllnessPhase 2NCT03477903
TAK-954 in Critically Ill Participants With Enteral Feeding Intolerance (EFI)
A Phase 2 study testing TAK-954, Metoclopramide and Normal Saline in people with Critical Illness and Enteral Nutrition, run by Millennium Pharmaceuticals, Inc. at 44 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Enteral Nutrition, Enteral Feeding Intolerance
- What is being tested?
- TAK-954, Metoclopramide and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 44 sitesin 4 countries
- Study dates
- 25 Aug 2018to 29 Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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]).
Trial locations and contacts
44 sites in 4 countries.
44 sites in 4 countries
United States14 sites
Anne Arundel Medical Center
Annapolis, Maryland, 21401
Joseph M Still Burn Centers
Augusta, Georgia, 30909
Cleveland Clinic
Cleveland, Ohio, 44195
Duke University Medical Center
Durham, North Carolina, 27705
Englewood Hospital and Medical Center
Englewood, New Jersey, 07631
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Eastern Idaho Medical Consultants
Idaho Falls, Idaho, 83404
Truman Medical Center Hospital Hill
Kansas City, Missouri, 64108
University of Kentucky Health Care
Lexington, Kentucky, 40536
New York-Presbyterian Columbia University Medical Center
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Creighton University
Omaha, Nebraska, 68124
Illinois Lung & Critical Care Institute
Peoria, Illinois, 61606
Froedtert Hospital
Wauwatosa, Wisconsin, 53226
United Kingdom13 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, B15 2GW
Royal Sussex County Hospital
Brighton, England, BN2 5BE
University Hospitals Bristol NHS Foundation Trust
Bristol, England, BS2 8HW
Cardiff and Vale University Health Board
Cardiff, Wales, CF14 4XN
NHS Lothian
Edinburgh, Scotland, EH16 4SB
NHS Greater Glasgow and Clyde
Glasgow, Scotland, G42 9TY
The Leeds Teaching Hospitals NHS Trust
Leeds, England, LS9 7TF
Royal Liverpool University Hospital NHS Trust
Liverpool
The Royal London Hospital
London, England, E1 1BB
Royal Free London NHS Foundation Trust
London, England, NW3 2QG
Guy's and Saint Thomas' NHS Foundation Trust
London, England, SE1 7EH
King's College Hospital NHS Foundation Trust
London, England, SE5 9RS
Aneurin Bevan University Health Board
Newport, Wales, NP20 2UB
Australia10 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, 5042
Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4029
Monash Medical Centre
Clayton, Victoria, 3168
The Northern Hospital
Epping, Victoria, 3076
Frankston Hospital
Frankston, Victoria, 3199
Logan Hospital
Meadowbrook, Queensland, 4131
The Royal Melbourne Hospital
Parkville, Victoria, 3050
Mater Hospital Brisbane
South Brisbane, Queensland, 4101
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Canada7 sites
Hopital Charles-LeMoyne
Greenfield Park, Quebec, J4V 2H1
Kingston General Hospital
Kingston, Ontario, K7L 2V7
Hopital du Sacre-Coeur de Montreal
Monteal, Quebec, H4J 1C5
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Royal Columbian Hospital
New Westminster, British Columbia, V3L 3W4
Centre Hospitalier Universitaire de Quebec Hospital Centre Hospitalier de IUniversite Laval
Québec, Quebec, G1V 4G5
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
About this study
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
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.
Read the 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.
- Being tested
- TAK-954, Metoclopramide, Normal Saline
- Keywords
- Drug therapy
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-954Drug
TAK-954 infusion
MetoclopramideDrug
Metoclopramide infusion
Normal SalineDrug
0.9% sodium chloride for injection
| Study group | Role | What they receive |
|---|---|---|
| Group A: TAK-954 0.1 mg | Experimental | 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. Receives: Drug: TAK-954; Drug: Normal Saline |
| Group B: TAK-954 0.3 mg | Experimental | 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. Receives: Drug: TAK-954; Drug: Normal Saline |
| Group C: TAK-954 1.0 mg | Experimental | 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. Receives: Drug: TAK-954; Drug: Normal Saline |
| Group D: Metoclopramide 10 mg | Active comparator | 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. Receives: Drug: Metoclopramide; Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Days 1 to 5
Secondary outcomes (7)
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.
Measured: Days 1 to 14
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.
Measured: Days 1 to 5
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.
Measured: Days 1 to 5 and Days 1 to 14
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.
Measured: Days 1 to 14 or until resolution of EFI, whichever occurs first
Percentage of Participants Achieving at Least 80% of Daily Goal Calories
Measured: Days 1 to 14 or end of treatment
Percentage of Participants Achieving at Least 80% of Daily Goal Protein
Measured: Days 1 to 14 or end of treatment
Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954
Measured: Day 5 pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start25 Aug 2018
- Primary completion29 Aug 2018
- Study completion29 Aug 2018
Why it stopped: Insufficient enrollment; No safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03477903
- Sponsor's protocol ID
- TAK-954-2002
- Other IDs
- U1111-1208-1831, 2017-003206-41, 18/NE/0139, 2017
- Status last verified
- Sep 2019
- First submitted
- 19 Mar 2018
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03477903
- Acronym / sponsor ID
- TAK-954-2002
- Keywords
- Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient enrollment; No safety concerns
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Aug 2018 (actual)
- Primary completion
- 29 Aug 2018 (actual)
- Study completion
- 29 Aug 2018 (actual)
- First posted
- 27 Mar 2018 (actual)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A: TAK-954 0.1 mg | Experimental | Drug: TAK-954, Drug: Normal SalineTAK-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 B: TAK-954 0.3 mg | Experimental | Drug: TAK-954, Drug: Normal SalineTAK-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 | Experimental | Drug: TAK-954, Drug: Normal SalineTAK-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 | Active comparator | Drug: Metoclopramide, Drug: Normal SalineMetoclopramide 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-954TAK-954 infusion | Drug | Group A: TAK-954 0.1 mg, Group B: TAK-954 0.3 mg, Group C: TAK-954 1.0 mg |
| MetoclopramideMetoclopramide infusion | Drug | Group D: Metoclopramide 10 mg |
| Normal Saline0.9% sodium chloride for injection | Drug | Group A: TAK-954 0.1 mg, Group B: TAK-954 0.3 mg, Group C: TAK-954 1.0 mg, Group D: Metoclopramide 10 mg |
Primary outcome
Average Daily Protein Adequacy Over the First 5 Days of Treatment
Time frame: 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.
7 secondary outcomes
Average Daily Protein Adequacy Over the Study Treatment Period
Time frame: Days 1 to 14
Average Daily Change in 24-hour Gastric Residual Volume (GRV) Over the First 5 Days of Study Treatment
Time frame: Days 1 to 5
Average Daily Caloric Adequacy
Time frame: Days 1 to 5 and Days 1 to 14
Time to Resolution of Enteral Feeding Intolerance (EFI)
Time frame: Days 1 to 14 or until resolution of EFI, whichever occurs first
Percentage of Participants Achieving at Least 80% of Daily Goal Calories
Time frame: Days 1 to 14 or end of treatment
Percentage of Participants Achieving at Least 80% of Daily Goal Protein
Time frame: Days 1 to 14 or end of treatment
Ctrough: Observed Concentration at the End of a Dosing Interval of TAK-954
Time frame: Day 5 pre-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Millennium Pharmaceuticals, Inc.
44 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TAK-954, Metoclopramide and Normal Saline in people with Critical Illness and Enteral Nutrition, run by Millennium Pharmaceuticals, Inc. at 44 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, United Kingdom, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Daily Protein Adequacy Over the First 5 Days of Treatment (time frame: Days 1 to 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019; AzTrials last refreshed its copy on 7 Nov 2026.