The CRISIS Prevention Study

• Sponsor: Michael Dean (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00395161
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Seattle Children's Hospital (Other), Children's Hospital Los Angeles (Other), Arkansas Children's Hospital Research Institute (Other), Children's Hospital of Michigan (Other), University of Pittsburgh (Other), Children's National Research Institute (Other), University of California, Los Angeles (Other), Harborview Injury Prevention and Research Center (Other)
• Enrollment: 293
• Locations: 7
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 41.9
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Despite strict hand washing, sterile technique, and antibiotic-coated catheters, nosocomial infection and sepsis remain the leading acquired causes of morbidity and mortality in critically ill children. Subsequent use of antibiotics to treat nosocomial infection and sepsis is considered a major attributable factor in the rise of antibiotic-resistant organisms in this population of children. This study will use a double-blind, randomized, controlled trial design to test the hypothesis that daily prophylaxis with metoclopramide, zinc, selenium and glutamine will reduce nosocomial infection and sepsis in critically ill children.

Condition or Disease	Intervention/Treatment	Phase
Sepsis	Drug: Metoclopramide; Drug: Zinc; Dietary Supplement: Glutamine; Drug: Selenium; Other: saline; Other: sterile water; Other: selenium; Dietary Supplement: whey-protein	Phase 3

Detailed Description

Despite strict hand washing, sterile technique, and antibiotic-coated catheters, nosocomial infection and sepsis remain the leading acquired causes of morbidity and mortality in critically ill children. Subsequent use of antibiotics to treat nosocomial infection and sepsis is considered a major attributable factor in the rise of antibiotic-resistant organisms in this population of children. Presently, "prophylaxis" strategies are used to prevent stress-induced gastrointestinal bleeding; however, no "prophylaxis" strategy is used to prevent stress-induced nosocomial infection and sepsis. When left unopposed, the stress hormone, cortisol, induces lymphocyte apoptosis, lymphopenia, and immune insufficiency. Prolactin is the counter-regulatory stress hormone that prevents cortisol-induced apoptosis and immunosuppression. Zinc, selenium, and glutamine are also important in maintenance of lymphocyte health. Critically ill patients commonly develop hypoprolactinemia secondary to increased central nervous system dopaminergic activity, as well as zinc, selenium, and glutamine deficiency caused by increased utilization and decreased supply. Hypoprolactinemia can be prevented by metoclopramide, a dopamine 2 receptor antagonist commonly used as a prokinetic in children, and zinc, selenium, and glutamine deficiency can be prevented with enteral supplementation. This study will use a double-blind randomized controlled trial design to test the hypothesis that daily prophylaxis with metoclopramide, zinc, selenium and glutamine will reduce nosocomial infection and sepsis in critically ill children.

Study Design

• Study Type: Interventional
• Actual Enrollment: 293 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Critical Illness Stress-induced Immune Suppression Prevention Trial
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: zinc selenium glutamine metoclopramide metoclopramide, zinc, selenium, and glutamine	Drug: Metoclopramide; 0.2 mg/kg/dose IV every 12 hours; Other Names: Reglan ; Drug: Zinc; one enteral dose daily of zinc chloride (10 mg/day elemental zinc for infants < or equal to one year of age, and 20 mg/day elemental zinc for patients > 1 year of age); Dietary Supplement: Glutamine; one enteral dose daily of glutamine 0.3 gm/kg/day; Drug: Selenium; one enteral dose daily of selenium (40 μg for infants < 8 months of age, 60 μg for infants 8 to 12 months of age, 90 μg for children 1-3 years, 150 μg for children 4-8 years, 280 μg for children 9 to 13 years, and 400 μg for children > 13 years)
Placebo Comparator: enteral whey protein and IV saline saline, sterile water, whey protein	Other: saline; equivalent volume of intravenous saline; Other: sterile water; equivalent volume of sterile water; Other: selenium; equivalent volume of sterile water; Dietary Supplement: whey-protein; one enteral dose daily of whey-protein; Other Names: Beneprotein

Outcome Measures

Primary Outcome Measures

1. The Primary Endpoint of This Study is the Median Time Between Admission to the PICU and Occurrence of Nosocomial Infection or Clinical Sepsis in PICU Patients Who Have Endotracheal Tubes, Central Venous Catheters, or Urinary Catheters. [48 hours after admission until 5 days after discharged from the PICU]

Secondary Outcome Measures

1. Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days [48 hours after PICU admission till discharge from PICU]

2. Antibiotic-free Days [48 hours after admission until PICU discharge]

3. Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days) [from time of PICU admission till discharge from PICU]

   What is reported is the number of participants with counts qualifying as lymphopenia.

4. All-cause 28-day Mortality Rate. [28 days after admission to the PICU]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

During the initial accrual period for this study, prior to the first interim analysis, patients will be eligible for enrollment if they:

• are between 12 months and less than 18 years; AND

• are within the first 48 hours of the PICU admission; AND

• have an endotracheal tube, central venous catheter (new or old, tunneled or not tunneled), or Foley catheter; AND

• are anticipated to have an indwelling arterial or central venous catheter for blood sampling during the first three days of study enrollment.

After the Data Safety Monitoring Board (DSMB) conducts its first interim evaluation, after enrollment of approximately 200 subjects, a decision will be made by the DSMB concerning enrollment of subjects between 40 weeks gestational age and 12 months. If the DSMB approves enrollment of infants after the first interim analysis, then patients will be eligible for enrollment if they:

• are between 40 weeks gestational age and less than 18 years; AND

• are within the first 48 hours of the PICU admission; AND

• have an endotracheal tube, central venous catheter (new or old, tunneled or not tunneled), or Foley catheter; AND

• are anticipated to have an indwelling arterial or central venous catheter for blood sampling during the first three days of study enrollment.

Exclusion Criteria:

During the initial accrual period for this study, prior to the first interim analysis, patients will be ineligible for enrollment if ANY of the following is true or anticipated:

• are less than 1 year age; OR

• are greater than or equal to 18 years of age; OR

• have a known allergy to metoclopramide; OR

• planned removal of endotracheal tube, central venous catheter, AND Foley catheters, within 72 hours of study enrollment, OR

• suspected intestinal obstruction, OR

• intestinal surgery or bowel disruption, OR

• chronic metoclopramide therapy prior to enrollment, OR

• failure to enroll within 48 hours of PICU admission, OR

• readmission to PICU in the previous 28 days, OR

• previously enrolled in this study, OR

• lack of commitment to aggressive intensive care therapies.

After the Data Safety Monitoring Board (DSMB) conducts its first interim evaluation, after enrollment of approximately 200 subjects, a decision will be made by the DSMB concerning enrollment of subjects between 40 weeks gestational age and 12 months. If the DSMB approves enrollment of infants after the first interim analysis, then patients will be ineligible for enrollment if ANY of the following is true or anticipated:

• are less than 40 weeks gestational age; OR

• are greater than or equal to 18 years of age; OR

• have a known allergy to metoclopramide; OR

• planned removal of endotracheal tube, central venous catheter, AND Foley catheters, within 72 hours of study enrollment, OR

• suspected intestinal obstruction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Childrens Hospital of Los Angeles	Los Angeles	California	United States	90027
3	University of California Los Angeles Medical Center	Los Angeles	California	United States	90095
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
6	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
7	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Michael Dean
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Seattle Children's Hospital
• Children's Hospital Los Angeles
• Arkansas Children's Hospital Research Institute
• Children's Hospital of Michigan
• University of Pittsburgh
• Children's National Research Institute
• University of California, Los Angeles
• Harborview Injury Prevention and Research Center

Investigators

• Principal Investigator: Joseph Carcillo, MD, University of Pittsburgh Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Michael Dean, Data Coordinating Center Principal Investigator, University of Utah
• ClinicalTrials.gov Identifier: NCT00395161
• Other Study ID Numbers: U01HD049934
• First Posted: Nov 2, 2006
• Last Update Posted: Apr 18, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Michael Dean, Data Coordinating Center Principal Investigator, University of Utah: sepsis; prevention; mineral supplementation
• Additional relevant MeSH terms: Sepsis; Selenium; Metoclopramide

Study Results

Participant Flow

Recruitment Details	Dates of recruitment period: April 2007 - November 2009; Location: Pediatric Intensive Care Unit (PICU)
Pre-assignment Detail	Patients were stratified according to immunocompromised status prior to randomization.

Arm/Group Title	Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide	Enteral Whey Protein, IV Saline
Arm/Group Description	Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.	Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.
Period Title: Overall Study
STARTED	149	144
COMPLETED	149	144
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Daily Nutriceutical Supplementation	Whey Protein	Total
Arm/Group Description	Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.	Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.	Total of all reporting groups
Overall Participants	149	144	293
Age (Count of Participants)
<=18 years	149 100%	144 100%	293 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.9 (5.6)	8.4 (5.9)	8.1 (5.7)
Sex: Female, Male (Count of Participants)
Female	69 46.3%	79 54.9%	148 50.5%
Male	80 53.7%	65 45.1%	145 49.5%
Region of Enrollment (participants) [Number]
United States	149 100%	144 100%	293 100%
Immune Compromised at Study Entry (Number) [Number]
Immune compromised	14 9.4%	11 7.6%	25 8.5%
Immune Competent	135 90.6%	133 92.4%	268 91.5%

Outcome Measures

1. Primary Outcome

Title	The Primary Endpoint of This Study is the Median Time Between Admission to the PICU and Occurrence of Nosocomial Infection or Clinical Sepsis in PICU Patients Who Have Endotracheal Tubes, Central Venous Catheters, or Urinary Catheters.
Time Frame	48 hours after admission until 5 days after discharged from the PICU

Outcome Measure Data

Analysis Population Description

Intention to treat analysis of all randomized patients.

Arm/Group Title	Daily Nutriceutical Supplementation	Whey Protein
Arm/Group Description	Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.	Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.
Measure Participants	149	144
Median (95% Confidence Interval) [Days]	12.1	13.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daily Nutriceutical Supplementation, Whey Protein
	Comments	Null hypothesis was equal median time in both arms. Sample size calculated to yield 90% power to detect a significant effect, assuming inverse hazard rate of 1.5 using two-sided logrank test with alpha=0.05. This required recruitment until 263 patients with an event were enrolled (though the study was terminated early for futility by the DSMB).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Log Rank
	Comments	Two-sided logrank test was used, stratified by immune compromised status at study entry (a factor also used to stratify the study randomization)

2. Secondary Outcome

Title	Rate of Nosocomial Infection or Clinical Sepsis Per 100 Study Days
Time Frame	48 hours after PICU admission till discharge from PICU

Outcome Measure Data

Analysis Population Description

All randomized patients analyzed by intention to treat

Arm/Group Title	Daily Nutriceutical Supplementation	Whey Protein
Arm/Group Description	Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.	Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.
Measure Participants	149	144
Mean (95% Confidence Interval) [Mean number of events per 100 study days]	4.99	4.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daily Nutriceutical Supplementation, Whey Protein
	Comments	Null hypothesis of equal event rates in the two study arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Rate analysis (see comments)
	Comments	95% CIs were calculated for rates in each arm, and rates compared between arms, via approach of DR Cox, Biometrika (1953), vol 40, pp. 354-60.

3. Secondary Outcome

Title	Antibiotic-free Days
Time Frame	48 hours after admission until PICU discharge

Outcome Measure Data

Analysis Population Description

All randomized patients per intention to treat analysis

Arm/Group Title	Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide	Enteral Whey Protein, IV Saline
Arm/Group Description
Measure Participants	149	144
Median (Inter-Quartile Range) [Days]	1	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daily Nutriceutical Supplementation, Whey Protein
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Incidence of Prolonged Lymphopenia (Absolute Lymphocyte Count Less Than or Equal to 1,000/mm³ for > or Equal to 7 Days)
Description	What is reported is the number of participants with counts qualifying as lymphopenia.
Time Frame	from time of PICU admission till discharge from PICU

Outcome Measure Data

Analysis Population Description

All randomized patients (intention to treat analysis)

Arm/Group Title	Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide	Enteral Whey Protein, IV Saline
Arm/Group Description
Measure Participants	149	144
Number [participants]	5 3.4%	12 8.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daily Nutriceutical Supplementation, Whey Protein
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	All-cause 28-day Mortality Rate.
Time Frame	28 days after admission to the PICU

Outcome Measure Data

Analysis Population Description

This safety outcome was analyzed by treatment received, among a total of 284 children who received treatment and had known 28-day status.

Arm/Group Title	Enteral Zinc, Selenium, Glutamine, and IV Metoclopramide	Enteral Whey Protein, IV Saline
Arm/Group Description
Measure Participants	145	139
Number [participants]	15 10.1%	8 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daily Nutriceutical Supplementation, Whey Protein
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Adverse events were collected for 28 days.
Adverse Event Reporting Description	For adverse events, denominators reflect Safety Population of those patients receiving each treatment. Therefore, denominators are 148 patients receiving Daily Nutriceutical Supplementation and 139 patients receiving Whey Protein.
Arm/Group Title	Daily Nutriceutical Supplementation		Whey Protein
Arm/Group Description	Subjects assigned to this group received zinc (20 mg), selenium (40 mcg ages 1-3 yrs, 100 mcg age 3-5 yrs, 200 mcg age 5-12 yrs, 400 mcg adolescent), and glutamine (0.3 g/kg) each morning, and intravenous metoclopramide (0.2 mg/kg, maximum 10 mg) every 12 hrs.		Subjects assigned to the whey protein group received 0.3 g/kg beneprotein each morning and intravenous saline every 12 hrs.
All Cause Mortality
	Daily Nutriceutical Supplementation		Whey Protein
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Daily Nutriceutical Supplementation		Whey Protein
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/148 (49.3%)		70/139 (50.4%)
Cardiac disorders
Arrhythmia	0/148 (0%)	0	1/139 (0.7%)	1
Cardiac arrest	1/148 (0.7%)	1	4/139 (2.9%)	6
Cardiopulmonary arrest	1/148 (0.7%)	1	2/139 (1.4%)	3
Myocardial ischemia	1/148 (0.7%)	1	0/139 (0%)	0
Pericardial effusion	1/148 (0.7%)	1	1/139 (0.7%)	1
Congenital, familial and genetic disorders
Sickle cell anaemia	1/148 (0.7%)	1	0/139 (0%)	0
Endocrine disorders
Diabetes insipidus	0/148 (0%)	0	1/139 (0.7%)	1
Eye disorders
Cortical blindness	0/148 (0%)	0	1/139 (0.7%)	1
Gastrointestinal disorders
Abdominal distension	1/148 (0.7%)	1	0/139 (0%)	0
GI bleed	0/148 (0%)	0	1/139 (0.7%)	1
Gastrointestinal bleeding	0/148 (0%)	0	1/139 (0.7%)	1
Intra-abdominal hemorrhage	0/148 (0%)	0	1/139 (0.7%)	1
Ischemic colitis	1/148 (0.7%)	1	0/139 (0%)	0
Pancreatitis	2/148 (1.4%)	2	1/139 (0.7%)	1
Peritonitis	1/148 (0.7%)	1	0/139 (0%)	0
General disorders
Brain death	2/148 (1.4%)	2	0/139 (0%)	0
Fever	1/148 (0.7%)	1	0/139 (0%)	0
Hyperthermia	1/148 (0.7%)	1	0/139 (0%)	0
Multiple organ failure	2/148 (1.4%)	2	1/139 (0.7%)	1
Withdrawal syndrome	1/148 (0.7%)	1	0/139 (0%)	0
Infections and infestations
Bacteremia	0/148 (0%)	0	1/139 (0.7%)	1
Catheter site cellulitis	1/148 (0.7%)	1	0/139 (0%)	0
Encephalitis viral	0/148 (0%)	0	1/139 (0.7%)	1
Nosocomial infection	43/148 (29.1%)	73	41/139 (29.5%)	61
Sepsis	13/148 (8.8%)	14	20/139 (14.4%)	29
Tracheitis	1/148 (0.7%)	1	0/139 (0%)	0
Urinary tract infection	0/148 (0%)	0	1/139 (0.7%)	1
Injury, poisoning and procedural complications
Brain herniation	0/148 (0%)	0	1/139 (0.7%)	1
Subdural haematoma	1/148 (0.7%)	1	0/139 (0%)	0
Investigations
Amylase high	1/148 (0.7%)	1	0/139 (0%)	0
Blood creatinine increased	1/148 (0.7%)	1	0/139 (0%)	0
Blood culture positive	0/148 (0%)	0	1/139 (0.7%)	1
Blood potassium decreased	1/148 (0.7%)	1	0/139 (0%)	0
CSF WBC increased	0/148 (0%)	0	1/139 (0.7%)	1
Culture stool positive	1/148 (0.7%)	1	0/139 (0%)	0
Culture urine positive	1/148 (0.7%)	1	0/139 (0%)	0
Decreased INR	0/148 (0%)	0	1/139 (0.7%)	1
Lipase increased	1/148 (0.7%)	1	0/139 (0%)	0
Oxygen saturation decreased	1/148 (0.7%)	1	0/139 (0%)	0
PCO2 increased	0/148 (0%)	0	2/139 (1.4%)	2
WBC increased	0/148 (0%)	0	1/139 (0.7%)	1
Metabolism and nutrition disorders
Hyperkalemia	0/148 (0%)	0	1/139 (0.7%)	1
Hypoglycemia	1/148 (0.7%)	1	0/139 (0%)	0
Hyponatremia	0/148 (0%)	0	1/139 (0.7%)	1
Hypovolemia	0/148 (0%)	0	1/139 (0.7%)	1
Metabolic acidosis	1/148 (0.7%)	1	0/139 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia recurrent	0/148 (0%)	0	1/139 (0.7%)	1
Nervous system disorders
Cerebral edema	2/148 (1.4%)	2	1/139 (0.7%)	1
Cerebral infarct	0/148 (0%)	0	1/139 (0.7%)	1
Choreoathetoid movements	0/148 (0%)	0	2/139 (1.4%)	2
Consciousness decreased	0/148 (0%)	0	1/139 (0.7%)	1
Edema cerebral	0/148 (0%)	0	1/139 (0.7%)	1
Headache	0/148 (0%)	0	1/139 (0.7%)	1
Intracranial hemorrhage	0/148 (0%)	0	1/139 (0.7%)	1
Intracranial pressure increased	2/148 (1.4%)	2	1/139 (0.7%)	1
Ischemic stroke	1/148 (0.7%)	1	0/139 (0%)	0
Shaking	1/148 (0.7%)	1	0/139 (0%)	0
Psychiatric disorders
Acute mental status changes	0/148 (0%)	0	1/139 (0.7%)	1
Agitation	0/148 (0%)	0	1/139 (0.7%)	1
Mental status changes	1/148 (0.7%)	1	0/139 (0%)	0
Renal and urinary disorders
Anuria	1/148 (0.7%)	1	0/139 (0%)	0
Hemorrhagic cystitis	1/148 (0.7%)	1	0/139 (0%)	0
Oliguria	1/148 (0.7%)	1	0/139 (0%)	0
Renal failure NOS	0/148 (0%)	0	1/139 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
ARDS	0/148 (0%)	0	1/139 (0.7%)	1
Acute respiratory distress syndrome	1/148 (0.7%)	1	1/139 (0.7%)	1
Acute respiratory failure	0/148 (0%)	0	1/139 (0.7%)	1
Cough	0/148 (0%)	0	1/139 (0.7%)	1
Failure respiratory	1/148 (0.7%)	1	0/139 (0%)	0
Hypoxemia	1/148 (0.7%)	1	0/139 (0%)	0
Hypoxia	1/148 (0.7%)	1	2/139 (1.4%)	2
Paralysis of diaphragm	1/148 (0.7%)	1	0/139 (0%)	0
Pleural effusion	0/148 (0%)	0	3/139 (2.2%)	3
Pulmonary edema	1/148 (0.7%)	1	0/139 (0%)	0
Pulmonary hemorrhage	1/148 (0.7%)	1	0/139 (0%)	0
Respiratory distress	1/148 (0.7%)	1	1/139 (0.7%)	1
Respiratory failure	4/148 (2.7%)	4	2/139 (1.4%)	2
Stridor	2/148 (1.4%)	2	0/139 (0%)	0
Vascular disorders
Acute hypotension	0/148 (0%)	0	1/139 (0.7%)	1
Hypotension	2/148 (1.4%)	2	1/139 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Daily Nutriceutical Supplementation		Whey Protein
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	119/148 (80.4%)		112/139 (80.6%)
Blood and lymphatic system disorders
Anemia	9/148 (6.1%)	10	10/139 (7.2%)	11
Coagulopathy	8/148 (5.4%)	8	4/139 (2.9%)	4
Leukocytosis	10/148 (6.8%)	11	10/139 (7.2%)	10
Cardiac disorders
Bradycardia	17/148 (11.5%)	19	14/139 (10.1%)	15
Tachycardia	11/148 (7.4%)	12	20/139 (14.4%)	24
Gastrointestinal disorders
Abdominal distension	8/148 (5.4%)	8	7/139 (5%)	8
Constipation	21/148 (14.2%)	21	15/139 (10.8%)	15
Diarrhea	13/148 (8.8%)	13	10/139 (7.2%)	13
Emesis	19/148 (12.8%)	25	17/139 (12.2%)	22
Vomiting	6/148 (4.1%)	7	10/139 (7.2%)	10
General disorders
Fever	13/148 (8.8%)	13	13/139 (9.4%)	15
Hyperthermia	10/148 (6.8%)	12	9/139 (6.5%)	14
Hypothermia	10/148 (6.8%)	19	8/139 (5.8%)	8
Pyrexia	16/148 (10.8%)	22	14/139 (10.1%)	18
Infections and infestations
Nosocomial infection	8/148 (5.4%)	9	10/139 (7.2%)	13
Sepsis	8/148 (5.4%)	8	7/139 (5%)	11
Investigations
BUN increased	11/148 (7.4%)	12	8/139 (5.8%)	9
Blood albumin decreased	4/148 (2.7%)	4	8/139 (5.8%)	8
Blood magnesium decreased	15/148 (10.1%)	16	10/139 (7.2%)	11
Blood phosphorus decreased	13/148 (8.8%)	17	13/139 (9.4%)	14
Blood potassium decreased	11/148 (7.4%)	11	11/139 (7.9%)	13
Blood sodium decreased	6/148 (4.1%)	6	7/139 (5%)	8
Hematocrit decreased	12/148 (8.1%)	13	10/139 (7.2%)	10
Hemoglobin decreased	13/148 (8.8%)	14	10/139 (7.2%)	17
Lipase increased	13/148 (8.8%)	14	5/139 (3.6%)	5
Oxygen saturation decreased	18/148 (12.2%)	20	13/139 (9.4%)	15
PCO2 increased	3/148 (2%)	5	8/139 (5.8%)	11
Platelets decreased	6/148 (4.1%)	7	7/139 (5%)	8
Metabolism and nutrition disorders
Acidosis	5/148 (3.4%)	7	8/139 (5.8%)	9
Hyperglycemia	21/148 (14.2%)	27	19/139 (13.7%)	21
Hyperkalemia	5/148 (3.4%)	5	8/139 (5.8%)	10
Hypernatremia	11/148 (7.4%)	12	8/139 (5.8%)	11
Hypocalcemia	4/148 (2.7%)	5	8/139 (5.8%)	10
Hypokalemia	26/148 (17.6%)	30	27/139 (19.4%)	41
Hypomagnesemia	5/148 (3.4%)	6	7/139 (5%)	12
Hyponatremia	7/148 (4.7%)	8	11/139 (7.9%)	13
Hypophosphatemia	5/148 (3.4%)	5	8/139 (5.8%)	9
Nervous system disorders
Seizure	3/148 (2%)	4	7/139 (5%)	7
Psychiatric disorders
Agitation	18/148 (12.2%)	18	18/139 (12.9%)	19
Renal and urinary disorders
Oliguria	8/148 (5.4%)	9	8/139 (5.8%)	11
Respiratory, thoracic and mediastinal disorders
Atelectasis	16/148 (10.8%)	18	17/139 (12.2%)	20
Hypoxia	8/148 (5.4%)	10	9/139 (6.5%)	12
Pleural effusion	8/148 (5.4%)	8	11/139 (7.9%)	16
Respiratory distress	7/148 (4.7%)	8	13/139 (9.4%)	21
Stridor	8/148 (5.4%)	8	6/139 (4.3%)	6
Tachypnea	6/148 (4.1%)	6	13/139 (9.4%)	14
Skin and subcutaneous tissue disorders
Skin breakdown	7/148 (4.7%)	11	8/139 (5.8%)	15
Vascular disorders
Hypertension	23/148 (15.5%)	24	16/139 (11.5%)	19
Hypotension	32/148 (21.6%)	37	32/139 (23%)	39

Limitations/Caveats

The Data Safety Monitoring Board met on November 30, 2009. Interim analysis of the first 273 patients was presented. Per the Board's recommendations, the study was terminated based on futility.

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.