Critically IllPhase 4NCT02459275

PEP uP Protocol in Surgical Patients

A Phase 4 study testing PEP uP Protocol and Metoclopramide in people with Critically Ill, run by Clinical Evaluation Research Unit at Kingston General Hospital at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Critically Ill
What is being tested?: PEP uP Protocol and Metoclopramide
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 4 sitesUnited States
Study dates: Jul 2015to Sep 2017
Phase: Phase 4
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

Age ≥ 18 years
ICU admission within past 48 hours
Initiation of tube feeds currently planned by the surgical ICU (SICU) team and primary surgical team
Admitted by a surgical service to the SICU (not a medical ICU or neurology patient)
Expected to remain mechanically ventilated for > 24 h and expected to require ICU care for > 72 h after screening

Who cannot join

Pregnancy
Attending surgeon preference (they must agree to feeding their patient according to the protocol in either arm using the goal rate determined by the SICU team and the nutritionist)
Contraindication to enteral nutrition (bowel obstruction, bowel discontinuity, proximal enterocutaneous fistula, and short gut syndrome)
Do not resuscitate (DNR) status or goals of care that specify limitations in medical therapies
Death expected within 24 hours

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Jamaica Hospital Medical Center
Jamaica, New York, 11418
Virginia Tech Carilion School of Medicine
Roanoke, Virginia, 24016

Other trials in United States

About this study

Official title: PEP uP Protocol (Enhanced Protein-Energy Provision Via the Enteral roUte Feeding Protocol) in Surgical Patients

The main objective of this project is to asses for safety, feasibility and effectiveness of an aggressive feeding protocol, PEP uP (Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol) in increasing protein and energy delivery to critically ill surgical patients. Our hypothesis is that an aggressive feeding protocol, PEP uP will be safe, acceptable, and effectively increase protein and energy delivery to critically ill surgical patients.

Read the detailed description

Gross underfeeding or iatrogenic malnutrition is prevalent in intensive care units throughout the world. Critically ill patients only receive, on average, 40-50% of their prescribed nutritional requirements. Inadequate provision of nutrition to these patients is associated with increased complications, prolonged length of stay in the ICU and hospital, and increased mortality. There are good data from large scale observational studies and randomized trials that suggest better fed patients have better clinical and economic outcomes and there are ICUs that consistently reach an average of 80-90% nutritional adequacy (amount of nutrition received over amount prescribed) thus it appears to be a feasible goal.

The PEP uP protocol (Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol) includes a new, innovative approach that protocolizes an aggressive set of strategies to providing enteral nutrition (EN) and shifts the paradigm from reactionary to proactive followed by de-escalation if nutrition therapy is not needed. The key components of this new PEP uP protocol are the following:

Starting feeds at the target rate based on increasing evidence that some patients tolerate starting nutrition at a higher rate of delivery and that slow start ups are not necessary.
Allowing "trophic feeds" a low volume of a concentrated feeding solution for 24 hours or longer, designed to maintain gastrointestinal structure and function for those patients who are deemed unsuitable for high volume intragastric feeds.
Prescribing semi-elemental feeding solution instead of a standard polymeric solution. These can then be changed to more traditional polymeric solution once the patient is tolerating adequate amounts of nutrition.
Prescribing protein supplements at initiation of EN and then discontinue if EN is well tolerated and protein requirement are met through their standard EN.
Starting motility agents at the same time EN is started with a re-evaluation in the days following to see if it is necessary.

This PEP uP protocol has been previously studied in two published studies enrolling primarily medical patients. In the first study, a pilot before and after trial, the protocol seemed to be feasible, safe, and acceptable to critical care nurses. No incidents compromising patient safety were observed. (Heyland 2010) Rates of vomiting, regurgitation, aspiration, and pneumonia were similar and the PEP uP group received significantly more energy and protein (when they were prescribed to receive full volume as opposed to "trophic"). A subsequent multi-center cluster randomized trial involving low-performing ICUs likewise demonstrated that intervention sites had improvements in energy and protein delivery as well as a decrease in average time from ICU admission to start of enteral nutrition compared to the control group. (Heyland 2013).

Conditions: Critically Ill
Being tested: PEP uP Protocol, Metoclopramide
Keywords: feeding protocol, enteral nutrition protocol, critically ill, surgical ICU, enteral nutrition, nutrition 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.

PEP uP ProtocolOther
Semi-elemental tube feeds are started at the hourly goal rate as determined by the 24 hour volume goal. Protein supplements will be started at the initiation of tube feeds to target a daily delivery of 2 g/kg/day.
MetoclopramideDrug
Also called Reglan
Metoclopramide 10mg Intravenous (IV) every 6 hours (q6h) or 5mg IV q6h for renal failure will be started empirically concomitant with EN initiation. Gastric Residual Volume (GRV) will be checked every 4 hours and will be reinfused to the patient each time it is checked.

Study groups in NCT02459275
Study group	Role	What they receive
PEP uP Protocol	Experimental	Participants will receive the PEP uP protocol with the pro motility agent. The intervention will be provided until the tube feeds are stopped or patient is fed meals orally and will be tracked until hospital discharge or 60 days which ever occur first. Receives: Other: PEP uP Protocol; Drug: Metoclopramide
Standard of Care	No intervention	Standard formula polymeric tube feeds started at a rate of 20 ml/hour. Gastric residual volume (GRV) will be checked every 4 hours. GRV is reinfused to the patient each time it is checked. GRV threshold is 200-500 ml. If the patient is tolerating tube feeds as determined by measuring the GRV, the rate is advanced by 20 ml/hour every 4 hours up to the goal rate. Participants will be followed until the tube feeds are stopped or patient is fed meals orally and will be tracked until hospital discharge or 60 days which ever occur first.

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Amount of Protein Received
The total amount of protein received from either EN or parenteral nutrition (PN), inclusive of propofol, divided by the amount prescribed as per the baseline assessment and expressed as a percentage.
Measured: 12 days
Total Amount of Energy
The total amount of energy received from either EN or parenteral nutrition (PN), inclusive of propofol, divided by the amount prescribed as per the baseline assessment and expressed as a percentage.
Measured: 12 days

Secondary outcomes (4)

Time to Initiation of Enteral Nutrition
Hours from intensive care unit (ICU) admission
Measured: 12 days
ICU Length of Stay
Days in the intensive care unit
Measured: up to 60 days
Mortality
Number of participants that died
Measured: up to 60 days
Hospital Length of Stay
Days the participants were in the admitted in the hospital
Measured: up to 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2015Sep 2017

First posted2 Jun 2015 (estimated)
Study startJul 2015
Primary completionSep 2017
Study completionSep 2017

Why it stopped: Funding discontinued

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.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Critically IllStudies 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 4
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02459275
Sponsor's protocol ID: PEP uP Surgical RCT
Status last verified: Oct 2020
First submitted: 27 May 2015
Last updated: 27 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Heyland DK, Cahill NE, Dhaliwal R, Wang M, Day AG, Alenzi A, Aris F, Muscedere J, Drover JW, McClave SA. Enhanced protein-energy provision via the enteral route in critically ill patients: a single center feasibility trial of the PEP uP protocol. Crit Care. 2010;14(2):R78. doi: 10.1186/cc8991. Epub 2010 Apr 29.
PubMed 20429886
Heyland DK, Murch L, Cahill N, McCall M, Muscedere J, Stelfox HT, Bray T, Tanguay T, Jiang X, Day AG. Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial. Crit Care Med. 2013 Dec;41(12):2743-53. doi: 10.1097/CCM.0b013e31829efef5.
PubMed 23982032
Heyland DK, Dhaliwal R, Lemieux M, Wang M, Day AG. Implementing the PEP uP Protocol in Critical Care Units in Canada: Results of a Multicenter, Quality Improvement Study. JPEN J Parenter Enteral Nutr. 2015 Aug;39(6):698-706. doi: 10.1177/0148607114531787. Epub 2014 Apr 18.
PubMed 24748597
McCall M, Cahill N, Murch L, Sinuff T, Bray T, Tanguay T, Heyland DK. Lessons Learned From Implementing a Novel Feeding Protocol: Results of a Multicenter Evaluation of Educational Strategies. Nutr Clin Pract. 2014 Aug;29(4):510-517. doi: 10.1177/0884533614531047. Epub 2014 Apr 22.
PubMed 24757062

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Critically Ill trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PEP uP Protocol (Enhanced Protein-Energy Provision Via the Enteral roUte Feeding Protocol) in Surgical Patients
ClinicalTrials.gov ID: NCT02459275
Acronym / sponsor ID: PEP uP Surgical RCT
Conditions: Critically Ill
Keywords: feeding protocol, enteral nutrition protocol, critically ill, surgical ICU, enteral nutrition, nutrition therapy
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Funding discontinued
Enrolment: 36 participants (actual)
Lead sponsor: Clinical Evaluation Research Unit at Kingston General HospitalUniversity, hospital or other
Collaborators: Nestle Health Science
Study start: Jul 2015
Primary completion: Sep 2017 (actual)
Study completion: Sep 2017 (actual)
First posted: 2 Jun 2015 (estimated)
Results: Posted 27 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Starting feeds at the target rate based on increasing evidence that some patients tolerate starting nutrition at a higher rate of delivery and that slow start ups are not necessary.
Allowing "trophic feeds" a low volume of a concentrated feeding solution for 24 hours or longer, designed to maintain gastrointestinal structure and function for those patients who are deemed unsuitable for high volume intragastric feeds.
Prescribing semi-elemental feeding solution instead of a standard polymeric solution. These can then be changed to more traditional polymeric solution once the patient is tolerating adequate amounts of nutrition.
Prescribing protein supplements at initiation of EN and then discontinue if EN is well tolerated and protein requirement are met through their standard EN.
Starting motility agents at the same time EN is started with a re-evaluation in the days following to see if it is necessary.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
PEP uP Protocol	Experimental	Other: PEP uP Protocol, Drug: MetoclopramideParticipants will receive the PEP uP protocol with the pro motility agent. The intervention will be provided until the tube feeds are stopped or patient is fed meals orally and will be tracked until hospital discharge or 60 days which ever occur first.
Standard of Care	No intervention	–Standard formula polymeric tube feeds started at a rate of 20 ml/hour. Gastric residual volume (GRV) will be checked every 4 hours. GRV is reinfused to the patient each time it is checked. GRV threshold is 200-500 ml. If the patient is tolerating tube feeds as determined by measuring the GRV, the rate is advanced by 20 ml/hour every 4 hours up to the goal rate. Participants will be followed until the tube feeds are stopped or patient is fed meals orally and will be tracked until hospital discharge or 60 days which ever occur first.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Age ≥ 18 years
ICU admission within past 48 hours
Initiation of tube feeds currently planned by the surgical ICU (SICU) team and primary surgical team
Admitted by a surgical service to the SICU (not a medical ICU or neurology patient)
Expected to remain mechanically ventilated for > 24 h and expected to require ICU care for > 72 h after screening

Key exclusion criteria (5 listed)

Pregnancy
Attending surgeon preference (they must agree to feeding their patient according to the protocol in either arm using the goal rate determined by the SICU team and the nutritionist)
Contraindication to enteral nutrition (bowel obstruction, bowel discontinuity, proximal enterocutaneous fistula, and short gut syndrome)
Do not resuscitate (DNR) status or goals of care that specify limitations in medical therapies
Death expected within 24 hours

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
PEP uP ProtocolSemi-elemental tube feeds are started at the hourly goal rate as determined by the 24 hour volume goal. Protein supplements will be started at the initiation of tube feeds to target a daily delivery of 2 g/kg/day.	Other	PEP uP Protocol
MetoclopramideAlso: ReglanMetoclopramide 10mg Intravenous (IV) every 6 hours (q6h) or 5mg IV q6h for renal failure will be started empirically concomitant with EN initiation. Gastric Residual Volume (GRV) will be checked every 4 hours and will be reinfused to the patient each time it is checked.	Drug	PEP uP Protocol

Primary outcome

Total Amount of Protein Received
Time frame: 12 days
The total amount of protein received from either EN or parenteral nutrition (PN), inclusive of propofol, divided by the amount prescribed as per the baseline assessment and expressed as a percentage.
Total Amount of Energy
Time frame: 12 days
The total amount of energy received from either EN or parenteral nutrition (PN), inclusive of propofol, divided by the amount prescribed as per the baseline assessment and expressed as a percentage.

4 secondary outcomes

Time to Initiation of Enteral Nutrition
Time frame: 12 days
ICU Length of Stay
Time frame: up to 60 days
Mortality
Time frame: up to 60 days
Hospital Length of Stay
Time frame: up to 60 days

Results and safety

Results posted to the registry on 27 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PEP uP Protocol	19	19
Standard of Care	17	17

Primary outcome: Total Amount of Protein Received

Time frame: 12 days. Mean (Standard Deviation). Unit: percentage of protein

Measure	PEP uP Protocol n = 19	Standard of Care n = 17
Value	55.1 (24.4)	52.9 (23.2)

Primary outcome: Total Amount of Energy

Time frame: 12 days. Mean (Standard Deviation). Unit: percentage of energy

Measure	PEP uP Protocol n = 19	Standard of Care n = 17
Value	49.4 (23.7)	60.3 (22.8)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 60 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PEP uP Protocol	1 of 19 (5.3%)	0 of 19 (0%)	1 of 19
Standard of Care	0 of 17 (0%)	0 of 17 (0%)	2 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20429886Heyland DK, Cahill NE, Dhaliwal R, Wang M, Day AG, Alenzi A, Aris F, Muscedere J, Drover JW, McClave SA. Enhanced protein-energy provision via the enteral route in critically ill patients: a single center feasibility trial of the PEP uP protocol. Crit Care. 2010;14(2):R78. doi: 10.1186/cc8991. Epub 2010 Apr 29.
Background: PubMed 23982032Heyland DK, Murch L, Cahill N, McCall M, Muscedere J, Stelfox HT, Bray T, Tanguay T, Jiang X, Day AG. Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial. Crit Care Med. 2013 Dec;41(12):2743-53. doi: 10.1097/CCM.0b013e31829efef5.
Background: PubMed 24748597Heyland DK, Dhaliwal R, Lemieux M, Wang M, Day AG. Implementing the PEP uP Protocol in Critical Care Units in Canada: Results of a Multicenter, Quality Improvement Study. JPEN J Parenter Enteral Nutr. 2015 Aug;39(6):698-706. doi: 10.1177/0148607114531787. Epub 2014 Apr 18.
Background: PubMed 24757062McCall M, Cahill N, Murch L, Sinuff T, Bray T, Tanguay T, Heyland DK. Lessons Learned From Implementing a Novel Feeding Protocol: Results of a Multicenter Evaluation of Educational Strategies. Nutr Clin Pract. 2014 Aug;29(4):510-517. doi: 10.1177/0884533614531047. Epub 2014 Apr 22.
Critical Care Nutrition website including information on the PEP uP ProtocolLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Critically Ill

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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.

Daren K Heyland, MD study director

Clinical Evaluation Research Unit

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing PEP uP Protocol and Metoclopramide in people with Critically Ill, run by Clinical Evaluation Research Unit at Kingston General Hospital at 4 sites in United States.

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 5 inclusion and 5 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 27 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 27 Oct 2020). 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?

Total Amount of Protein Received (time frame: 12 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02459275, which also lists 4 linked publications.

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 27 Oct 2020; AzTrials last refreshed its copy on 29 Oct 2026.