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