Critically IllPEPuPNCT01167595
Enhanced Protein-Energy Provision Via the Enteral Route in Critically Ill Patients
A study testing PEP uP Protocol in people with Critically Ill, run by Clinical Evaluation Research Unit at Kingston General Hospital at 18 sites in 2 countries.
Trial summary
Critically ill patients are consistently underfed. Feeding protocols are standardized system tools used to guide nutrition practices, but to date have failed to improve delivery of nutrition. The PEP uP Protocol is a new enhanced feeding protocol. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critically Ill
- What is being tested?
- PEP uP Protocol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,059 participants
- Where
- 18 sitesin 2 countries
- Study dates
- Sep 2010to Nov 2011
- Phase
- Interventional
- 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
- Critically ill adults (i.e. >18 years of age)
- Mechanically ventilated before or within the first 6 hours of admission to ICU
Who cannot join
- Nutrition (either EN or Parenteral Nutrition (PN)) started before admission to ICU
- Not intubated within 6 hours of admission to ICU
- Receiving non-invasive ventilation (i.e. mask ventilation) during the first 6 hours of ICU stay
- Moribund (as evidenced by death within 48 hours of admission to ICU)
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States9 sites
Henry Ford Macomb Hospital
Clinton Township, Michigan
Nassau University Medical Center
East Meadow, New York
Lakes Region General Hospital
Laconia, New Hampshire
Medical Center of the Rockies
Loveland, Colorado
Phoenix Veterans Affairs Health Care System
Phoenix, Arizona
Vassar Brothers Medical Center
Poughkeepsie, New York
South Texas Veterans Health Care System Audie L. Murphy Division
San Antonio, Texas
CoxHealth
Springfield, Missouri
Washington Health Center
Washington D.C., District of Columbia, 20010
Canada9 sites
Rouge Valley Health System - Ajax and Pickering Site
Ajax, Ontario
William Osler Health Centre - Brampton Civic Campus
Brampton, Ontario
Foothills Medical Centre
Calgary, Alberta
William Osler Health Centre - Etobicoke Campus
Etobicoke, Ontario
St Joseph's Healthcare
Hamilton, Ontario, L8N 4A6
The Credit Valley Hospital
Mississauga, Ontario
Pasqua Hospital
Regina, Saskatchewan
Rouge Valley Health System - Centenary Site
Scarborough Village, Ontario
St Paul's Hospital
Vancouver, British Columbia
About this study
Official title: A Multicenter, Cluster Randomized Trial of Enhanced Protein-Energy Provision Via the Enteral Route Feeding Protocol in Critically Ill Patients: The PEP uP Protocol
Critically ill patients are consistently underfed. Feeding protocols are standardized system tools used to guide nutrition practices, but to date have failed to improve delivery of nutrition. The PEP uP Protocol is a new enhanced feeding protocol. Twenty North American Intensive Care Units (ICUs) will assess baseline nutrition practices. Ten ICUs will be randomized to implement the PEP uP Protocol and educational intervention, and ten will be randomized to continue usual care. Nutrition practices will be reevaluated 6 months after baseline. The investigators hypothesize that the PEP uP Protocol will increase delivery of nutrition, and may ultimately lead to improved survival of critical illness.
Read the detailed description
There is a well known and well described relationship between malnutrition, immune dysfunction, and infection. Critically ill patients are often hypermetabolic and can rapidly become nutritionally compromised. Repeated efforts over the past few years have not significantly improved the amount of calories delivered via the enteral route. Historically, feeding protocols have been used to guide the delivery of enteral nutrition (EN) but they frequently utilize conservative, reactionary approaches to optimizing nutrition.
We propose a new, innovative approach that protocolizes an aggressive set of strategies to providing 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 protocol are the following: 1) 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. For patients who are hemodynamically stable, we propose to shift from an hourly rate target goal to a 24 hour volume goal and give nurses guidance on how to make up this volume if there was an interruption for non-gastrointestinal reasons. This 'volume-based' goal represents a significant shift in practice from traditional fixed hourly rate goals to a new protocol in which nurses can increase the hourly rate depending on how many hours they have left in the day to ensure that the patient receives the 24 hour volume within the day. 2) For patients who are deemed unsuitable for high volume intragastric feeds, we provide an option to initiate 'trophic feeds.' Trophic feeds represent an idea to provide a low volume of a concentrated feeding solution for 24 hours or longer, designed to maintain gastrointestinal structure and function rather than meet their protein and caloric goals. This option should reduce the numbers of patients ordered to be kept nil per os (NPO). Thus, PEP uP patients may gain some of the benefit of early EN. 3) To optimize tolerance in the early phase of critical illness, we propose to use a semi elemental feeding solution instead of a standard polymeric solution. There is some evidence that these semi elemental solutions are better assimilated than polymeric solutions in the critical care setting. These solutions can be changed to a more traditional polymeric solution once the patient is tolerating adequate amounts of nutrition. 4) Rather than wait for a protein debt to accumulate because of inadequate delivery of EN, protein supplements are prescribed at initiation of EN and can be discontinued if EN is well tolerated and they are receiving all their protein requirements through their standard EN. This strategy guarantees that the patient will most likely receive all their protein requirements in the early phase of their critical illness. 5) Rather than wait for a problem with gastrointestinal tolerance to develop, we propose to start motility agents at the same time EN is started with a re-evaluation in the days following to see if it is necessary. By preventing delayed gastric emptying, which frequently occurs in this patient population, we can improve nutritional adequacy. 6) Based on emerging evidence that a higher gastric residual volume (the volume of feeds remaining in the stomach when the bedside nurse aspirates the feeding tube) is safe and perhaps results in greater nutritional adequacy, we will include a higher gastric residual volume of 300ml in our protocol. It has been shown in one randomized trial that a feeding protocol that starts a motility agent empirically at the time of initiation of feeds and uses a higher threshold for a critical gastric residual volume (250 ml) improves nutritional adequacy.
Since the bedside nurses initiate and utilize feeding protocols to achieve target goals, we will couple this newer generational feeding protocol with a comprehensive nurse-directed nutritional educational intervention that will focus on its safe and effective implementation. This focus on nursing nutrition education represents a major shift away from traditional education which has focused on dietitians and physicians.
Our hypothesis is that this aggressive feeding protocol combined with a nurse-directed nutrition educational intervention will be safe, acceptable, and effectively increase protein and energy delivery to critically ill patients. We postulate that this increased provision of calories and protein may translate into improved clinical outcomes, particularly for the patients at the extremes of weight, but the current study is not powered to demonstrate such a difference.
- Conditions
- Critically Ill
- Being tested
- PEP uP Protocol
- Keywords
- Critically ill, Nutrition therapy, Enteral nutrition
- 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
Protocol documents (i.e. pre-printed order, algorithm for advancing feed, and algorithm for calculating rate of administering feed as per 24hour volume) and a slide presentation coupled with educational reminders (posters and bedside notices) and practice helps (tool to remind nurse to measure and report nutritional adequacy) will be made available to all nurses, in bedside manuals and/or on the local intranet.
| Study group | Role | What they receive |
|---|---|---|
| PEP uP Protocol | Experimental | PEP-uP protocol and treatment algorithm implemented for all patients in ICU. Receives: Other: PEP uP Protocol |
| Standard Feeding Protocol | No intervention | Enteral feeds are guided by a standard feeding protocol specified by pre-printed ICU admission orders. The admitting physician has the option of initiating the enteral feeding protocol or keeping the patient nil per os (NPO). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Prescribed Calories From Energy
Total calories received from enteral nutrition/total prescription up to 12 evaluable ICU days
Measured: first 12 days
Percentage of Prescribed Protein
Total protein received from enteral nutrition/total prescription up to 12 evaluable ICU days
Measured: first 12 days
Secondary outcomes (3)
Timeliness of Initiation of EN
Time of the initiation of EN from ICU admit
Measured: 60 days
Percentage of Participants With Vomiting
Measured: 60 days
Percentage of Participants With Pneumonia
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2010 (estimated)
- Study startSep 2010
- Primary completionNov 2011
- Study completionNov 2011
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 (2)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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,059 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinical Evaluation Research Unit at Kingston General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Responsible party
- Principal investigator, Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
- Investigators
- Daren K Heyland, MD, Principal investigator, Clinical Evaluation Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01167595
- Sponsor's protocol ID
- PEPuP cRCT
- Acronym
- PEPuP
- Status last verified
- Apr 2021
- First submitted
- 20 Jul 2010
- Last updated
- 28 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- 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 20429886Heyland 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
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Cluster Randomized Trial of Enhanced Protein-Energy Provision Via the Enteral Route Feeding Protocol in Critically Ill Patients: The PEP uP Protocol
- ClinicalTrials.gov ID
- NCT01167595
- Acronym / sponsor ID
- PEPuP / PEPuP cRCT
- Conditions
- Critically Ill
- Keywords
- Critically ill, Nutrition therapy, Enteral nutrition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,059 participants (actual)
- Lead sponsor
- Clinical Evaluation Research Unit at Kingston General HospitalUniversity, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Study start
- Sep 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 22 Jul 2010 (estimated)
- Results
- Posted 6 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Critically ill patients are consistently underfed. Feeding protocols are standardized system tools used to guide nutrition practices, but to date have failed to improve delivery of nutrition. The PEP uP Protocol is a new enhanced feeding protocol. Twenty North American Intensive Care Units (ICUs) will assess baseline nutrition practices. Ten ICUs will be randomized to implement the PEP uP Protocol and educational intervention, and ten will be randomized to continue usual care. Nutrition practices will be reevaluated 6 months after baseline. The investigators hypothesize that the PEP uP Protocol will increase delivery of nutrition, and may ultimately lead to improved survival of critical illness.
Detailed description
There is a well known and well described relationship between malnutrition, immune dysfunction, and infection. Critically ill patients are often hypermetabolic and can rapidly become nutritionally compromised. Repeated efforts over the past few years have not significantly improved the amount of calories delivered via the enteral route. Historically, feeding protocols have been used to guide the delivery of enteral nutrition (EN) but they frequently utilize conservative, reactionary approaches to optimizing nutrition.
We propose a new, innovative approach that protocolizes an aggressive set of strategies to providing 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 protocol are the following: 1) 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. For patients who are hemodynamically stable, we propose to shift from an hourly rate target goal to a 24 hour volume goal and give nurses guidance on how to make up this volume if there was an interruption for non-gastrointestinal reasons. This 'volume-based' goal represents a significant shift in practice from traditional fixed hourly rate goals to a new protocol in which nurses can increase the hourly rate depending on how many hours they have left in the day to ensure that the patient receives the 24 hour volume within the day. 2) For patients who are deemed unsuitable for high volume intragastric feeds, we provide an option to initiate 'trophic feeds.' Trophic feeds represent an idea to provide a low volume of a concentrated feeding solution for 24 hours or longer, designed to maintain gastrointestinal structure and function rather than meet their protein and caloric goals. This option should reduce the numbers of patients ordered to be kept nil per os (NPO). Thus, PEP uP patients may gain some of the benefit of early EN. 3) To optimize tolerance in the early phase of critical illness, we propose to use a semi elemental feeding solution instead of a standard polymeric solution. There is some evidence that these semi elemental solutions are better assimilated than polymeric solutions in the critical care setting. These solutions can be changed to a more traditional polymeric solution once the patient is tolerating adequate amounts of nutrition. 4) Rather than wait for a protein debt to accumulate because of inadequate delivery of EN, protein supplements are prescribed at initiation of EN and can be discontinued if EN is well tolerated and they are receiving all their protein requirements through their standard EN. This strategy guarantees that the patient will most likely receive all their protein requirements in the early phase of their critical illness. 5) Rather than wait for a problem with gastrointestinal tolerance to develop, we propose to start motility agents at the same time EN is started with a re-evaluation in the days following to see if it is necessary. By preventing delayed gastric emptying, which frequently occurs in this patient population, we can improve nutritional adequacy. 6) Based on emerging evidence that a higher gastric residual volume (the volume of feeds remaining in the stomach when the bedside nurse aspirates the feeding tube) is safe and perhaps results in greater nutritional adequacy, we will include a higher gastric residual volume of 300ml in our protocol. It has been shown in one randomized trial that a feeding protocol that starts a motility agent empirically at the time of initiation of feeds and uses a higher threshold for a critical gastric residual volume (250 ml) improves nutritional adequacy.
Since the bedside nurses initiate and utilize feeding protocols to achieve target goals, we will couple this newer generational feeding protocol with a comprehensive nurse-directed nutritional educational intervention that will focus on its safe and effective implementation. This focus on nursing nutrition education represents a major shift away from traditional education which has focused on dietitians and physicians.
Our hypothesis is that this aggressive feeding protocol combined with a nurse-directed nutrition educational intervention will be safe, acceptable, and effectively increase protein and energy delivery to critically ill patients. We postulate that this increased provision of calories and protein may translate into improved clinical outcomes, particularly for the patients at the extremes of weight, but the current study is not powered to demonstrate such a difference.
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 ProtocolPEP-uP protocol and treatment algorithm implemented for all patients in ICU. |
| Standard Feeding Protocol | No intervention | –Enteral feeds are guided by a standard feeding protocol specified by pre-printed ICU admission orders. The admitting physician has the option of initiating the enteral feeding protocol or keeping the patient nil per os (NPO). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Critically ill adults (i.e. >18 years of age)
- Mechanically ventilated before or within the first 6 hours of admission to ICU
Key exclusion criteria (4 listed)
- Nutrition (either EN or Parenteral Nutrition (PN)) started before admission to ICU
- Not intubated within 6 hours of admission to ICU
- Receiving non-invasive ventilation (i.e. mask ventilation) during the first 6 hours of ICU stay
- Moribund (as evidenced by death within 48 hours of admission to ICU)
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 ProtocolProtocol documents (i.e. pre-printed order, algorithm for advancing feed, and algorithm for calculating rate of administering feed as per 24hour volume) and a slide presentation coupled with educational reminders (posters and bedside notices) and practice helps (tool to remind nurse to measure and report nutritional adequacy) will be made available to all nurses, in bedside manuals and/or on the local intranet. | Other | PEP uP Protocol |
Primary outcome
Percentage of Prescribed Calories From Energy
Time frame: first 12 days
Total calories received from enteral nutrition/total prescription up to 12 evaluable ICU days
Percentage of Prescribed Protein
Time frame: first 12 days
Total protein received from enteral nutrition/total prescription up to 12 evaluable ICU days
3 secondary outcomes
Timeliness of Initiation of EN
Time frame: 60 days
Percentage of Participants With Vomiting
Time frame: 60 days
Percentage of Participants With Pneumonia
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- 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.
- Results publication: 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.
- websiteLink provided by the sponsor.
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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 principal investigator
Clinical Evaluation Research Unit
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PEP uP Protocol in people with Critically Ill, run by Clinical Evaluation Research Unit at Kingston General Hospital at 18 sites in 2 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 2 inclusion and 4 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: finished, as of the sponsor's last update on 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2021). 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?
Percentage of Prescribed Calories From Energy (time frame: first 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 NCT01167595, which also lists 2 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 28 Apr 2021.