PEP uP Protocol in Surgical Patients

• Sponsor: Clinical Evaluation Research Unit at Kingston General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02459275
• Collaborator: Nestle Health Science (Other)
• Enrollment: 36
• Locations: 4
• Arms: 2
• Duration (Months): 26.1
• Patients Per Site: 9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Critically Ill	Other: PEP uP Protocol; Drug: Metoclopramide	Phase 4

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:

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.

2. 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.

3. 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.

1. Prescribing protein supplements at initiation of EN and then discontinue if EN is well tolerated and protein requirement are met through their standard EN.

2. 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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: PEP uP Protocol (Enhanced Protein-Energy Provision Via the Enteral roUte Feeding Protocol) in Surgical Patients
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEP uP Protocol 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.	Other: PEP uP Protocol; 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.; Drug: Metoclopramide; 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.; Other Names: Reglan
No Intervention: Standard of Care 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.

Outcome Measures

Primary Outcome Measures

1. Total Amount of Protein Received [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.

2. Total Amount of Energy [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.

Secondary Outcome Measures

1. Time to Initiation of Enteral Nutrition [12 days]

   Hours from intensive care unit (ICU) admission

2. ICU Length of Stay [up to 60 days]

   Days in the intensive care unit

3. Mortality [up to 60 days]

   Number of participants that died

4. Hospital Length of Stay [up to 60 days]

   Days the participants were in the admitted in the hospital

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Jamaica Hospital Medical Center	Jamaica	New York	United States	11418
4	Virginia Tech Carilion School of Medicine	Roanoke	Virginia	United States	24016

Sponsors and Collaborators

• Clinical Evaluation Research Unit at Kingston General Hospital
• Nestle Health Science

Investigators

• Study Director: Daren K Heyland, MD, Clinical Evaluation Research Unit

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 11, 2017

More Information

Additional Information:

• Critical Care Nutrition website including information on the PEP uP Protocol

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.
• 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.
• 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.
• 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. Epub 2014 Apr 22.

• Responsible Party: Daniel D Yeh, MD, Daniel Dante Yeh, MD, University of Miami
• ClinicalTrials.gov Identifier: NCT02459275
• Other Study ID Numbers: PEP uP Surgical RCT
• First Posted: Jun 2, 2015
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Daniel D Yeh, MD, Daniel Dante Yeh, MD, University of Miami: feeding protocol; enteral nutrition protocol; critically ill; surgical ICU; enteral nutrition; nutrition therapy
• Additional relevant MeSH terms: Critical Illness; Metoclopramide

Study Results

Participant Flow

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Period Title: Overall Study
STARTED	19	17
COMPLETED	19	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	PEP uP Protocol	Standard of Care	Total
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.	Total of all reporting groups
Overall Participants	19	17	36
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.1 (24.7)	50.6 (15.6)	49.8 (0.75)
Sex: Female, Male (Count of Participants)
Female	1 5.3%	5 29.4%	6 16.7%
Male	18 94.7%	12 70.6%	30 83.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Total Amount of Protein Received
Description	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.
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Mean (Standard Deviation) [percentage of protein]	55.1 (24.4)	52.9 (23.2)

2. Primary Outcome

Title	Total Amount of Energy
Description	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.
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Mean (Standard Deviation) [percentage of energy]	49.4 (23.7)	60.3 (22.8)

3. Secondary Outcome

Title	Time to Initiation of Enteral Nutrition
Description	Hours from intensive care unit (ICU) admission
Time Frame	12 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Mean (Inter-Quartile Range) [hours]	26.7	28.2

4. Secondary Outcome

Title	ICU Length of Stay
Description	Days in the intensive care unit
Time Frame	up to 60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Mean (Inter-Quartile Range) [days]	12	12.5

5. Secondary Outcome

Title	Mortality
Description	Number of participants that died
Time Frame	up to 60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Count of Participants [Participants]	1 5.3%	2 11.8%

6. Secondary Outcome

Title	Hospital Length of Stay
Description	Days the participants were in the admitted in the hospital
Time Frame	up to 60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PEP uP Protocol	Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.	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.
Measure Participants	19	17
Mean (Inter-Quartile Range) [days]	21.4	16.6

Adverse Events

Time Frame	60 days
Arm/Group Title	PEP uP Protocol		Standard of Care
Arm/Group Description	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. PEP uP Protocol: 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. Metoclopramide: 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.		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.
All Cause Mortality
	PEP uP Protocol		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		2/17 (11.8%)
Serious Adverse Events
	PEP uP Protocol		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		0/17 (0%)
Cardiac disorders
temporary QTC prolongation	1/19 (5.3%)	1	0/17 (0%)	0
Other (Not Including Serious) Adverse Events
	PEP uP Protocol		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.