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| Name | Class |
|---|---|
| Children's Hospital Medical Center, Cincinnati | OTHER |
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The purpose of the study is 1) to determine whether administration of intravenous zinc to critically ill children is safe, and 2) to determine an appropriate dose of zinc supplementation.
Our recently published studies in children with septic shock demonstrated that pediatric septic shock is characterized by large scale repression of genes that either directly depend on normal zinc homeostasis or directly participate in zinc homeostasis. Functional validation studies demonstrated that nonsurvivors of pediatric septic shock have abnormally low serum zinc concentrations. A follow-up pilot study in a general population of critically ill children demonstrated that the presence of low plasma zinc concentrations is a prevalent problem in critically ill children. In addition, low plasma zinc concentrations correlate inversely with indices of inflammation and directly with the number of organ failures. These preliminary data, coupled with the expected safety of zinc supplementation, provided the rationale for a double blinded, prospective, placebo-controlled trial of zinc supplementation in critically ill children, with the two primary study endpoints to assess efficacy being highly clinically relevant: reduction of the lymphopenia rate and improvement of glucose homeostasis. Although the proposal was well-received, the primary concern precluding funding of this trial were lack of safety and dosing data for intravenous zinc. We have therefore developed a proposal for a Phase I/II study of safety and pharmacokinetics to address these concerns. It is anticipated that data generated through this proposal will provide the necessary preliminary data to re-submit our application for an interventional efficacy trial of zinc supplementation in critically ill children
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | No Intervention | No intervention | |
| Low dose group | Active Comparator | 250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days |
|
| Medium dose group | Active Comparator | 500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days |
|
| High dose group | Active Comparator | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zinc sulfate | Drug | Zinc sulfate 200 mcg/ml in Normal Saline |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Zinc Concentration Over Time | Plasma Zinc levels were measured daily during the seven day study period in each group. | 7 days |
| New Fever | Because of reports of fever in patients wiht zinc overdoses, we monitored patients for new fever while on supplementation | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose Homeostasis | Patients were assigned a score based on glucose range to take into account the degree of hyperglycemia as well as the need for insulin over the course of the 7 day study period. This score is an ordinal scale ranging from 1 to 5, with a score of 1 indicating no hyperglycemia, and 5 indicating severe hyperglycemia despite insulin administration. | 7 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Natalie Z Cvijanovich, MD | UCSF Benioff Children's Hospital Oakland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens' Hospital & Research Center Oakland | Oakland | California | 94611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19057435 | Background | Cvijanovich NZ, King JC, Flori HR, Gildengorin G, Wong HR. Zinc homeostasis in pediatric critical illness. Pediatr Crit Care Med. 2009 Jan;10(1):29-34. doi: 10.1097/PCC.0b013e31819371ce. | |
| 17374846 | Background | Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, Kalyanaraman M, Tofil NM, Penfil S, Monaco M, Tagavilla MA, Odoms K, Dunsmore K, Barnes M, Aronow BJ; Genomics of Pediatric SIRS/Septic Shock Investigators. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007 Jul 18;30(2):146-55. doi: 10.1152/physiolgenomics.00024.2007. Epub 2007 Mar 20. |
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One patient was enrolled but withdrawn by PI due to insufficient intravenous access to obtain study labs
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Group | No intervention |
| FG001 | Low Dose Group | 250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| FG002 | Medium Dose Group | 500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| FG003 | High Dose Group | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Group | No intervention |
| BG001 | Low Dose Group | 250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Zinc Concentration Over Time | Plasma Zinc levels were measured daily during the seven day study period in each group. | Posted | Mean | Standard Deviation | mcg/dL | 7 days |
|
28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Group | No intervention |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Refractory hypoxemia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | One patient developed refractory hypoxemia and had to be cannulated for extracorporeal membrane oxygenation on study day 6. He recovered and survived |
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Small sample size in each group, with multiple comparisons. The study population was varied in age and diagnosis. Plasma zinc does not reflect total body zinc status, therefore a patient with low plasma Zn may not have true zinc deficiency.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Natalie Cvijanovich, MD | UCSF Benioff Childrens Hospital Oakland | 510-428-3784 | NCvijanovich@mail.cho.org |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D019287 | Zinc Sulfate |
| ID | Term |
|---|---|
| D013431 | Sulfates |
| D013464 | Sulfuric Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
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| BG002 | Medium Dose Group | 500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| BG003 | High Dose Group | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Pediatric Risk of Mortality (PRISM) III | PRISM is Pediatric Risk of Mortality score The PRISM score has 17 physiologic variables subdivided into 26 ranges. The score for each variable is summed to determine the PRISM score. The minimum score (lowest risk of mortality) is 0 and the maximum score is 70. | Median | Inter-Quartile Range | units on a scale |
|
| Pediatric Index of Mortality (PIM) | PIM, or pediatric index of mortality, is a mortality prediction model for children in intensive care. It inputs seven variables and produces a calculated percentage mortality risk ranging from 0-100% | Median | Inter-Quartile Range | percentage mortality risk |
|
| Pediatric Logistic Organ Dysfunction (PELOD ) | The PeLOD (Pediatric Logistic Organ Dysfunction) score is a measure of multiple organ dysfunction that sums values for 6 organ systems (cardiovascular, respiratory, renal, hepatic, hematologic, and neurologic) to give a number between 0 and 71. The higher the number the worse the organ dysfunction and the greater the risk of mortality. | Median | Inter-Quartile Range | units on a scale |
|
| Number of patients with >= 2 organs failed | Number | participants |
|
| OG003 | High Dose Group | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline |
|
|
| Primary | New Fever | Because of reports of fever in patients wiht zinc overdoses, we monitored patients for new fever while on supplementation | Posted | Number | participants | 7 days |
|
|
|
|
| Secondary | Glucose Homeostasis | Patients were assigned a score based on glucose range to take into account the degree of hyperglycemia as well as the need for insulin over the course of the 7 day study period. This score is an ordinal scale ranging from 1 to 5, with a score of 1 indicating no hyperglycemia, and 5 indicating severe hyperglycemia despite insulin administration. | Posted | Median | Inter-Quartile Range | units on a scale | 7 days |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Low Dose Group | 250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline | 1 | 6 | 0 | 6 |
| EG002 | Medium Dose Group | 500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline | 0 | 6 | 0 | 6 |
| EG003 | High Dose Group | 750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days Zinc sulfate: Zinc sulfate 200 mcg/ml in Normal Saline | 0 | 6 | 0 | 6 |
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| D007287 |
| Inorganic Chemicals |
| D017967 | Zinc Compounds |
| Day 2 |
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| Day 3 |
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| Day 4 |
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| Day 5 |
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| Day 6 |
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| Day 7 |
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