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Enhanced Protein-Energy Provision Via the Enteral Route in Critically Ill Patients

A Multicenter, Cluster Randomized Trial of Enhanced Protein-Energy Provision Via the Enteral Route Feeding Protocol in Critically Ill Patients: The PEP uP Protocol

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01167595
Acronym
PEPuP
Enrollment
1059
Registered
2010-07-22
Start date
2010-09-30
Completion date
2011-11-30
Last updated
2021-04-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Critically Ill

Keywords

Critically ill, Nutrition therapy, Enteral nutrition

Brief 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. 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.

Interventions

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.

Sponsors

Société des Produits Nestlé (SPN)
CollaboratorINDUSTRY
Clinical Evaluation Research Unit at Kingston General Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Critically ill adults (i.e. \>18 years of age) * Mechanically ventilated before or within the first 6 hours of admission to ICU

Exclusion criteria

* 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)

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Prescribed Calories From Energyfirst 12 daysTotal calories received from enteral nutrition/total prescription up to 12 evaluable ICU days
Percentage of Prescribed Proteinfirst 12 daysTotal protein received from enteral nutrition/total prescription up to 12 evaluable ICU days

Secondary

MeasureTime frameDescription
Timeliness of Initiation of EN60 daysTime of the initiation of EN from ICU admit
Percentage of Participants With Vomiting60 days
Percentage of Participants With Pneumonia60 days

Countries

Canada, United States

Participant flow

Recruitment details

We conducted a cluster randomized trial of 18 ICUs in North America. Randomizing ICUs rather than individual patients was necessary to minimize the contamination of patients randomized to the usual care group who might have received care that was guided by the PEP uP protocol if it were operational in the same ICU at the same time

Participants by arm

ArmCount
PEP uP Protocol
PEP-uP protocol and treatment algorithm implemented for all patients in ICU. PEP uP Protocol: 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.
270
PEP uP Protocol
PEP-uP protocol and treatment algorithm implemented for all patients in ICU. PEP uP Protocol: 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.
9
Standard Feeding Protocol
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).
270
Standard Feeding Protocol
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).
9
Total558

Baseline characteristics

CharacteristicPEP uP ProtocolStandard Feeding ProtocolTotal
Age, Continuous
Baseline
65.1 years
STANDARD_DEVIATION 15.5
63.4 years
STANDARD_DEVIATION 15.1
64.2 years
STANDARD_DEVIATION 15.3
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
Canada
4 ICUs5 ICUs9 ICUs
Region of Enrollment
United States
5 ICUs4 ICUs9 ICUs
Sex: Female, Male
Baseline
Female
113 Participants100 Participants213 Participants
Sex: Female, Male
Baseline
Male
157 Participants170 Participants327 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 00 / 0
other
Total, other adverse events
0 / 00 / 0
serious
Total, serious adverse events
0 / 00 / 0

Outcome results

Primary

Percentage of Prescribed Calories From Energy

Total calories received from enteral nutrition/total prescription up to 12 evaluable ICU days

Time frame: first 12 days

Population: This was a pre- post cluster RCT where the same 9 ICUs evaluated before and after randomization but the individuals at the ICUs are different. Some outcomes were analyzed at the ICU level while others were analyzed at the participant level. Ergo 522 is the total of 270 participants at baseline + 252 at follow up in the Pep up arm. Similarly in the standard feeding protocol 537= 270 at baseline + 267 at follow up

ArmMeasureGroupValue (MEAN)Dispersion
PEP uP ProtocolPercentage of Prescribed Calories From EnergyBaseline time32 percentage of prescriptionStandard Deviation 29.4
PEP uP ProtocolPercentage of Prescribed Calories From EnergyFollow-up time43.6 percentage of prescriptionStandard Deviation 32.1
Standard Feeding ProtocolPercentage of Prescribed Calories From EnergyBaseline time34.2 percentage of prescriptionStandard Deviation 30.9
Standard Feeding ProtocolPercentage of Prescribed Calories From EnergyFollow-up time33.6 percentage of prescriptionStandard Deviation 29.5
Primary

Percentage of Prescribed Protein

Total protein received from enteral nutrition/total prescription up to 12 evaluable ICU days

Time frame: first 12 days

Population: This was a pre- post cluster RCT where the same 9 ICUs evaluated before and after randomization but the individuals at the ICUs are different. Some outcomes were analyzed at the ICU level while others were analyzed at the participant level. Ergo 522 is the total of 270 participants at baseline + 252 at follow up in the Pep up arm. Similarly in the standard feeding protocol 537= 270 at baseline + 267 at follow up

ArmMeasureGroupValue (MEAN)Dispersion
PEP uP ProtocolPercentage of Prescribed ProteinBaseline time33.6 percentage of prescriptionStandard Deviation 31.1
PEP uP ProtocolPercentage of Prescribed ProteinFollow-up time47.4 percentage of prescriptionStandard Deviation 34.7
Standard Feeding ProtocolPercentage of Prescribed ProteinBaseline time34.2 percentage of prescriptionStandard Deviation 30.9
Standard Feeding ProtocolPercentage of Prescribed ProteinFollow-up time33.6 percentage of prescriptionStandard Deviation 29.5
Secondary

Percentage of Participants With Pneumonia

Time frame: 60 days

Population: This was a pre- post cluster RCT where the same 9 ICUs evaluated before and after randomization but the individuals at the ICUs are different. Some outcomes were analyzed at the ICU level while others were analyzed at the participant level. Ergo 522 is the total of 270 participants at baseline + 252 at follow up in the Pep up arm. Similarly in the standard feeding protocol 537= 270 at baseline + 267 at follow up

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PEP uP ProtocolPercentage of Participants With PneumoniaBaseline time6 Participants
PEP uP ProtocolPercentage of Participants With PneumoniaFollow-up time7 Participants
Standard Feeding ProtocolPercentage of Participants With PneumoniaFollow-up time16 Participants
Standard Feeding ProtocolPercentage of Participants With PneumoniaBaseline time11 Participants
Secondary

Percentage of Participants With Vomiting

Time frame: 60 days

Population: This was a pre- post cluster RCT where the same 9 ICUs evaluated before and after randomization but the individuals at the ICUs are different. Some outcomes were analyzed at the ICU level while others were analyzed at the participant level. Ergo 522 is the total of 270 participants at baseline + 252 at follow up in the Pep up arm. Similarly in the standard feeding protocol 537= 270 at baseline + 267 at follow up

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PEP uP ProtocolPercentage of Participants With VomitingBaseline time12 Participants
PEP uP ProtocolPercentage of Participants With VomitingFollow-up time14 Participants
Standard Feeding ProtocolPercentage of Participants With VomitingBaseline time20 Participants
Standard Feeding ProtocolPercentage of Participants With VomitingFollow-up time12 Participants
Secondary

Timeliness of Initiation of EN

Time of the initiation of EN from ICU admit

Time frame: 60 days

Population: This was a pre- post cluster RCT where the same 9 ICUs evaluated before and after randomization but the individuals at the ICUs are different. Some outcomes were analyzed at the ICU level while others were analyzed at the participant level. Ergo 522 is the total of 270 participants at baseline + 252 at follow up in the Pep up arm. Similarly in the standard feeding protocol 537= 270 at baseline + 267 at follow up

ArmMeasureGroupValue (MEAN)Dispersion
PEP uP ProtocolTimeliness of Initiation of ENBaseline time40.7 hoursStandard Deviation 30.6
PEP uP ProtocolTimeliness of Initiation of ENFollow-up time29.7 hoursStandard Deviation 31.4
Standard Feeding ProtocolTimeliness of Initiation of ENBaseline time33.6 hoursStandard Deviation 33.1
Standard Feeding ProtocolTimeliness of Initiation of ENFollow-up time35.2 hoursStandard Deviation 39.2

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026