Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents 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.

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