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

Septic Shock Clinical Trial

Official title:

Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01352182
• Other study ID #: PIOSEPSIS1217
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2011
• Est. completion date: January 2017

Study information

• Verified date: August 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

Drug:
• Pioglitazone hydrochloride
Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events	The number of hypoglycemic events in pioglitazone vs standard care. Hypoglycemia was defined as blood glucose level that remains <40mg/dl despite dextrose bolus treatment.	Assessement over five days
Primary	Safety Labs - Blood Urea Nitrogen (BUN)	BUN levels in blood from subject on the final day of enrollment	Final day of study
Primary	Safety Labs - Creatinine	Creatinine levels in blood from subject on the final day of enrollment	Final day of study
Primary	Safety Labs - Alanine Aminotransferase (ALT)	ALT levels in blood from subject on the final day of enrollment	Final day of study
Primary	Pioglitazone Area Under Curve Estimates by Treatment Group and Route of Administration	Pioglitazone concentration as the total area under curve divided by the number of days receiving the drug in subjects who took the drug by mouth versus by naso-gastric tube	five days
Secondary	Effect of Pioglitazone Area Under the Curve on Changes in IL-6	We examined the effect of pioglitazone Area under the curve on IL-6 in patients receiving pioglitazone only. (Control subjects did not receive pioglitazone). The pharmacokinetic endpoint was area under the curve (AUC) total/days of pioglitazone administration	Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study

External Links

•   Kaplan Lab Page