Safety and Dose Escalation Study of Zinc Supplementation in Critically Ill Children

UCSF Benioff Children's Hospital Oakland

Status and phase: Completed; Phase 2; Phase 1

Conditions: Critical Illness

Treatments: Drug: Zinc sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT01062009

SPID 0876

Details and patient eligibility

About

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.

Full description

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

Enrollment: 24 patients

Sex: All

Ages: 30 days to 10 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Admission to pediatric intensive care unit
• Age between 1 month and 10 years
• Pediatric Risk of Mortality III score > 5, OR presence of at least 1 new organ failure
• Anticipated pediatric intensive care unit length of stay > 3 days
• Ability of parent or legal guardian to provide informed consent

Exclusion criteria

• Known zinc deficiency
• Pre-existing bone marrow failure
• New or existing diagnosis of diabetes mellitus
• Limitation of care orders in place
• New diagnosis of brain injury, encephalopathy
• Clinical contraindication for zinc supplementation

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

Control group

No Intervention group

Description:

No intervention

Low dose group

Active Comparator group

Description:

250 mcg/kg/day supplemental IV zinc sulfate divided every 8 hours for 7 days

Treatment:

Drug: Zinc sulfate

Medium dose group

Active Comparator group

Description:

500 mcg/kg/day supplemental IV zinc sulfate q8 hours for 7 days

Treatment:

Drug: Zinc sulfate

High dose group

Active Comparator group

Description:

750 mcg/kg/day supplemental IV zinc sulfate q8 hrs for 7 days

Treatment:

Drug: Zinc sulfate