Severe SepsisPhase 1/2NCT01352182
Pharmacokinetic and Biomarker Study of Pioglitazone in Adolescents With Severe Sepsis and Septic Shock
A Phase 1/2 study testing Pioglitazone hydrochloride in people with Severe Sepsis and Septic Shock, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Severe Sepsis, Septic Shock
- What is being tested?
- Pioglitazone hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jan 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock
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.
Read the 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.
- Conditions
- Severe Sepsis, Septic Shock
- Being tested
- Pioglitazone hydrochloride
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone hydrochlorideDrug
Also called Actos
Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone hydrochloride | Experimental | Pioglitazone hydrochloride treatment group Receives: Drug: Pioglitazone hydrochloride |
| Normal standard care | No intervention | Normal standard care control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Assessement over five days
Safety Labs - Blood Urea Nitrogen (BUN)
BUN levels in blood from subject on the final day of enrollment
Measured: Final day of study
Safety Labs - Creatinine
Creatinine levels in blood from subject on the final day of enrollment
Measured: Final day of study
Safety Labs - Alanine Aminotransferase (ALT)
ALT levels in blood from subject on the final day of enrollment
Measured: 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
Measured: five days
Secondary outcomes (1)
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
Measured: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2011 (estimated)
- Study startOct 2011
- Primary completionMay 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Severe SepsisStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer M. Kaplan, M.D., M.S., Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01352182
- Sponsor's protocol ID
- PIOSEPSIS1217
- Status last verified
- Aug 2020
- First submitted
- 23 Feb 2011
- Last updated
- 2 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19760394Sherwin 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.
PubMed 21667139Kaplan 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.
PubMed 30255316
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Characteristics of Pioglitazone and Preliminary Biomarker Response in Adolescents Aged 12 to 17 Years With Severe Sepsis and Septic Shock
- ClinicalTrials.gov ID
- NCT01352182
- Acronym / sponsor ID
- PIOSEPSIS1217
- Conditions
- Severe Sepsis, Septic Shock
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- May 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 11 May 2011 (estimated)
- Results
- Posted 2 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone hydrochloride | Experimental | Drug: Pioglitazone hydrochloridePioglitazone hydrochloride treatment group |
| Normal standard care | No intervention | –Normal standard care control group |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pioglitazone hydrochlorideAlso: ActosParticipants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days. | Drug | Pioglitazone hydrochloride |
Primary outcome
Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events
Time frame: Assessement over five days
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.
Safety Labs - Blood Urea Nitrogen (BUN)
Time frame: Final day of study
BUN levels in blood from subject on the final day of enrollment
Safety Labs - Creatinine
Time frame: Final day of study
Creatinine levels in blood from subject on the final day of enrollment
Safety Labs - Alanine Aminotransferase (ALT)
Time frame: Final day of study
ALT levels in blood from subject on the final day of enrollment
Pioglitazone Area Under Curve Estimates by Treatment Group and Route of Administration
Time frame: five days
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
1 secondary outcome
Effect of Pioglitazone Area Under the Curve on Changes in IL-6
Time frame: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19760394Kaplan 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.
- Background: PubMed 21667139Sherwin 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.
- Results publication: PubMed 30255316Kaplan 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.
- Kaplan Lab PageLink provided by the sponsor.
Related trials for Severe Sepsis
RecruitingObservational study
Early Detection and Kinetics of Sepsis-Induced Coagulopathy in Severe Burn Patients
Sepsis, Sepsis-induced Coagulopathy
RecruitingObservational study
Early Detection and Kinetics of Sepsis-Induced Coagulopathy in Severe Burn Patients
Peer Bullying Intervention, Vodcast
Not yet recruitingObservational study
Blood Pressure Goal in Preterm Preeclampsia
Hypertensive Disorder of Pregnancy, Preeclampsia
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia
Recruiting
Efficacy and Safety of Methylene Blue in the Treatment of Severe Septic Shock
Septic Shock, Methylene Blue
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer M. Kaplan, M.D., M.S. principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pioglitazone hydrochloride in people with Severe Sepsis and Septic Shock, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events (time frame: Assessement over five days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01352182, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.