Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents With Severe Sepsis and Septic Shock
Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock
1 other identifier
interventional
12
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2011
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 23, 2011
CompletedFirst Posted
Study publicly available on registry
May 11, 2011
CompletedStudy Start
First participant enrolled
October 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2017
CompletedResults Posted
Study results publicly available
September 2, 2020
CompletedSeptember 2, 2020
August 1, 2020
4.6 years
February 23, 2011
November 27, 2018
August 18, 2020
Conditions
Outcome Measures
Primary Outcomes (5)
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
Safety Labs - Blood Urea Nitrogen (BUN)
BUN levels in blood from subject on the final day of enrollment
Final day of study
Safety Labs - Creatinine
Creatinine levels in blood from subject on the final day of enrollment
Final day of study
Safety Labs - Alanine Aminotransferase (ALT)
ALT levels in blood from subject on the final day of enrollment
Final day of study
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 Outcomes (1)
Effect of Pioglitazone Area Under the Curve on Changes in IL-6
Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study
Study Arms (2)
Pioglitazone hydrochloride
EXPERIMENTALPioglitazone hydrochloride treatment group
Normal standard care
NO INTERVENTIONNormal standard care control group
Interventions
Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Related 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.
PMID: 19760394BACKGROUNDSherwin 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.
PMID: 21667139BACKGROUNDKaplan 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.
PMID: 30255316RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Small sample size
Results Point of Contact
- Title
- Jennifer Kaplan
- Organization
- Cincinnati Children's Hospital Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer M. Kaplan, M.D., M.S.
Children's Hospital Medical Center, Cincinnati
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 23, 2011
First Posted
May 11, 2011
Study Start
October 1, 2011
Primary Completion
May 1, 2016
Study Completion
January 1, 2017
Last Updated
September 2, 2020
Results First Posted
September 2, 2020
Record last verified: 2020-08