Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents With Severe Sepsis and Septic Shock

Children's Hospital Medical Center, Cincinnati12 enrolled

Overview

The purpose of this study is to evaluate the pharmacokinetics of pioglitazone and to determine the effect on inflammatory biomarkers for pioglitazone in patients with severe sepsis and septic shock.

Severe sepsis is a major cause of morbidity and mortality among adults and children. Few clinical trials have demonstrated clinical benefit in sepsis. Severe sepsis is a systemic inflammatory syndrome in response to infection that is associated with acute organ dysfunction. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARg) is involved in the regulation of the sepsis-induced inflammatory response. The central hypothesis is that pioglitazone reduces the inflammatory responses in children with severe sepsis and septic shock.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Severe Sepsis Septic Shock

Interventions

Pioglitazone hydrochlorideDRUG

Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Weight range between 30 to less than or equal to 90kg * Have a known or suspected infection and meet criteria for severe sepsis or septic shock as defined according to the International Pediatric Sepsis Consensus Conference guidelines Exclusion Criteria: * Are in a moribund state in which death is perceived as imminent * Have an advanced directive or do not resuscitate order to withhold life-sustaining * Have a history of cyanotic heart disease or congestive heart failure * Have a serum transaminase level (ALT) that exceeds about 2.5 times the upper limit of normal (\>112 unit/L) * Are or become pregnant * Are already on or have a history of taking pioglitazone or rosiglitazone * Have type 1 or 2 diabetes * Have total body weight below 30 kg or above 90 kg * Have a serious condition, in addition to sepsis, which in the opinion of the investigator would compromise the participant

Locations (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events

The number of hypoglycemic events in pioglitazone vs standard care. Hypoglycemia was defined as blood glucose level that remains \<40mg/dl despite dextrose bolus treatment.

Time frame: Assessement over five days

Safety Labs - Blood Urea Nitrogen (BUN)

BUN levels in blood from subject on the final day of enrollment

Time frame: Final day of study

Safety Labs - Creatinine

Creatinine levels in blood from subject on the final day of enrollment

Time frame: Final day of study

Safety Labs - Alanine Aminotransferase (ALT)

ALT levels in blood from subject on the final day of enrollment

Time frame: Final day of study

Pioglitazone Area Under Curve Estimates by Treatment Group and Route of Administration

Pioglitazone concentration as the total area under curve divided by the number of days receiving the drug in subjects who took the drug by mouth versus by naso-gastric tube

Time frame: five days

Secondary Outcomes

Effect of Pioglitazone Area Under the Curve on Changes in IL-6

We examined the effect of pioglitazone Area under the curve on IL-6 in patients receiving pioglitazone only. (Control subjects did not receive pioglitazone). The pharmacokinetic endpoint was area under the curve (AUC) total/days of pioglitazone administration

Time frame: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study

Data from ClinicalTrials.gov

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