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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati Identifier:
First received: February 23, 2011
Last updated: January 26, 2016
Last verified: January 2016
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.

Condition Intervention Phase
Severe Sepsis
Septic Shock
Drug: Pioglitazone hydrochloride
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • 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).

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 21
Study Start Date: October 2011
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01352182

Contact: Jennifer M Kaplan, M.D., M.S. 513-636-4259
Contact: Kelli Howard, R.N. 513-636-4837

United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Jennifer M Kaplan, MD, MS    513-636-4259   
Principal Investigator: Jennifer M. Kaplan, M.D., M.S.         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Principal Investigator: Jennifer M. Kaplan, M.D., M.S. Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT01352182     History of Changes
Other Study ID Numbers: PIOSEPSIS1217 
Study First Received: February 23, 2011
Last Updated: January 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Shock, Septic
Pathologic Processes
Systemic Inflammatory Response Syndrome
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on May 26, 2016