Clinical trial NCT01352182: Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents With Severe Sepsis and Septic Shock
Official title: Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Severe Sepsis
Septic Shock
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2011-05-11
Enrollment: 12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events
timeFrame: Assessement over five days
measure: Safety Labs - Blood Urea Nitrogen (BUN)
timeFrame: Final day of study
measure: Safety Labs - Creatinine
timeFrame: Final day of study
measure: Safety Labs - Alanine Aminotransferase (ALT)
timeFrame: Final day of study
measure: Pioglitazone Area Under Curve Estimates by Treatment Group and Route of Administration
timeFrame: five days
Secondary outcomes:
measure: Effect of Pioglitazone Area Under the Curve on Changes in IL-6
timeFrame: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Jennifer M. Kaplan, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaplan JM, Denenberg A, Monaco M, Nowell M, Wong H, Zingarelli B. Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock. Intensive Care Med. 2010 Jan;36(1):123-30. doi: 10.1007/s00134-009-1654-6. Epub 2009 Sep 17.
citation: Sherwin CM, Ding L, Kaplan J, Spigarelli MG, Vinks AA. Optimal study design for pioglitazone in septic pediatric patients. J Pharmacokinet Pharmacodyn. 2011 Aug;38(4):433-47. doi: 10.1007/s10928-011-9202-8. Epub 2011 Jun 11.
citation: Kaplan JM, Zingarelli B, Krallman K, Tang Girdwood S, Lagory D, Mizuno T, Fei L, Wong HR, Vinks AA. Phase 1 safety and pharmacokinetic study on the use of pioglitazone in critically ill patients with sepsis: a randomized clinical trial. Intensive Care Med. 2018 Nov;44(11):2006-2008. doi: 10.1007/s00134-018-5374-7. Epub 2018 Sep 25. No abstract available.