Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents With Severe Sepsis and Septic Shock
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.
Drug: Pioglitazone hydrochloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock|
- Evaluate the pharmacokinetic and safety profile of pioglitazone in patients with severe sepsis and septic shock [ Time Frame: Pharmacokinetic (PK) data (clearance, volume of distribution and absorption rate) on day 1 (time 0.5, 2, 6 and 21h after drug dosing) ] [ Designated as safety issue: Yes ]Pharmacokinetic data will be assessed approximately as follows: Day 1 - time 0, 0.5, 2, 6, and 21hr after drug dosing; Day 2 - prior to dosing; Day 3 - prior to dosing and at 0.5, 2, 6, and 21h after drug dosing; Days 4-5 - prior to dosing. The primary PK parameters are clearance, volume of distribution and absorption rate. Safety data will be assessed throughout the days of drug dosing and the Pediatric Intensive Care Unit (PICU) stay, an expected average of about 2 weeks. Primary safety laboratory studies include glucose (measured every 6 hours), liver enzymes (daily), creatinine (daily), and blood urea nitrogen (daily).
- Examine the effect of pioglitazone treatment on inflammatory biomarkers of sepsis in patients with severe sepsis and septic shock [ Time Frame: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study ] [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
|Experimental: Pioglitazone hydrochloride||
Drug: Pioglitazone hydrochloride
Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.
Other Name: Actos
|No Intervention: Normal standard care|
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.
|Contact: Jennifer M Kaplan, M.D., M.S.||513-636-4259||Jennifer.Kaplan@cchmc.org|
|Contact: Eileen Beckman, R.N.||firstname.lastname@example.org|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Jennifer M Kaplan, MD, MS 513-636-4259 email@example.com|
|Principal Investigator: Jennifer M. Kaplan, M.D., M.S.|
|Principal Investigator:||Jennifer M. Kaplan, M.D., M.S.||Children's Hospital Medical Center, Cincinnati|