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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01352182
Recruitment Status : Completed
First Posted : May 11, 2011
Last Update Posted : January 9, 2017
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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.

Condition or disease Intervention/treatment Phase
Severe Sepsis Septic Shock Drug: Pioglitazone hydrochloride Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (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
Study Start Date : October 2011
Actual Primary Completion Date : May 2016
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis Shock
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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) ]
    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 :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01352182

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Principal Investigator: Jennifer M. Kaplan, M.D., M.S. Children's Hospital Medical Center, Cincinnati

Additional Information:
Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT01352182     History of Changes
Other Study ID Numbers: PIOSEPSIS1217
First Posted: May 11, 2011    Key Record Dates
Last Update Posted: January 9, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Shock, Septic
Systemic Inflammatory Response Syndrome
Pathologic Processes
Hypoglycemic Agents
Physiological Effects of Drugs