A Phase 1/2 interventional study of Pioglitazone hydrochloride in Severe Sepsis and Septic Shock, sponsored by Children's Hospital Medical Center, Cincinnati. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2020-09-02.
Sponsored by Children's Hospital Medical Center, Cincinnati · Phase 1/2, Interventional, and Treatment
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.
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.
1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.
This study's enrollment of 12 is below the median of 105 across 896 interventional studies indexed under Sepsis.
Browse Sepsis studies →Children's Hospital Medical Center, Cincinnati is the lead sponsor of 661 studies on the registry; 134 are open to participants now.
Of its 54 completed or terminated interventional studies of FDA-regulated products, 30 (56%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Pioglitazone hydrochloride treatment group
Drug: Pioglitazone hydrochloride
Normal standard care control group
Participants will receive a daily dose of pioglitazone at 0.5 mg/kg/dose for 5 days.
Also known as: Actos
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.
Time frame: Assessement over five days
Safety Labs - Blood Urea Nitrogen (BUN)
BUN levels in blood from subject on the final day of enrollment
Time frame: Final day of study
Safety Labs - Creatinine
Creatinine levels in blood from subject on the final day of enrollment
Time frame: Final day of study
Safety Labs - Alanine Aminotransferase (ALT)
ALT levels in blood from subject on the final day of enrollment
Time frame: 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
Time frame: five days
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
Time frame: Evaluation of inflammatory biomarkers will be obtained prior to dosing for the first five days of the study
| Milestone | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Started | 8 | 4 |
| Completed | 8 | 4 |
| Not completed | 0 | 0 |
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.
| events | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Evaluate the Safety Profile of Pioglitazone in Patients With Severe Sepsis and Septic Shock as the Number of Hypoglycemic Events | 0 | 0 |
BUN levels in blood from subject on the final day of enrollment
| mg/dl | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Safety Labs - Blood Urea Nitrogen (BUN) | 7.5 (6 to 18.75) | 10 (5.25 to 15.5) |
Creatinine levels in blood from subject on the final day of enrollment
| mg/dl | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Safety Labs - Creatinine | 0.72 (0.39 to 0.778) | 0.415 (0.305 to 0.593) |
ALT levels in blood from subject on the final day of enrollment
| U/L | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Safety Labs - Alanine Aminotransferase (ALT) | 21.5 (13.5 to 25.25) | 24.5 (11 to 27.5) |
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
| ng*h/ml | Pioglitazone Hydrochloride by Mouth | Pioglitazone Hydrochloride by Nasogastric Tube |
|---|---|---|
| Pioglitazone Area Under Curve Estimates by Treatment Group and Route of Administration | 5363 ± 2362 | 1052 ± 942 |
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
| ng/ml | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Effect of Pioglitazone Area Under the Curve on Changes in IL-6 | -1.4425 ± 0.3741 | NA ± NA |
Collected over Adverse events were monitored for each subject throughout each subject's hospitalization which ranged from 4 days to 30 days for control subjects and 4 days to 23 days for pioglitazone subjects.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pioglitazone Hydrochloride | 2/8 (25%) | 2/8 (25%) | 5/8 (62.5%) |
| Normal Standard Care | 0/4 (0%) | 0/4 (0%) | 2/4 (50%) |
| Event | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 2/8 | 0/4 |
| Acute kidney injuryRenal and urinary disorders | 1/8 | 0/4 |
| Severe biventricular dysfunctionCardiac disorders | 1/8 | 0/4 |
| mediastinal hemorrhageRespiratory, thoracic and mediastinal disorders | 1/8 | 0/4 |
| Surgical and medical procedures - OtherSurgical and medical procedures | 1/8 | 0/4 |
| ventricular tachycardiaCardiac disorders | 1/8 | 0/4 |
| ventricular fibrillationCardiac disorders | 1/8 | 0/4 |
| hemolysisBlood and lymphatic system disorders | 1/8 | 0/4 |
| intracranial hemorrhageNervous system disorders | 1/8 | 0/4 |
| Event | Pioglitazone Hydrochloride | Normal Standard Care |
|---|---|---|
| FeverGeneral disorders | 5/8 | 0/4 |
| AnemiaBlood and lymphatic system disorders | 3/8 | 2/4 |
| HypoalbuminemiaMetabolism and nutrition disorders | 4/8 | 2/4 |
| HypokalemiaMetabolism and nutrition disorders | 2/8 | 2/4 |
| HypophosphatemiaMetabolism and nutrition disorders | 3/8 | 1/4 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 3/8 | 0/4 |
| Complaint of chest painCardiac disorders | 0/8 | 1/4 |
| Sinus tachycardiaCardiac disorders | 1/8 | 1/4 |
| Adrenal insufficiencyEndocrine disorders | 1/8 | 1/4 |
| PancreatitisGastrointestinal disorders | 0/8 | 1/4 |
| Age, Continuous(years) | Pioglitazone Hydrochloride | Normal Standard Care | Total |
|---|---|---|---|
| Mean | 13.8 ± 3.5 | 20.8 ± 9.7 | 16.083 ± 6.721 |
| Sex: Female, Male(Participants) | Pioglitazone Hydrochloride | Normal Standard Care | Total |
|---|---|---|---|
| Female | 3 | 3 | 6 |
| Male | 5 | 1 | 6 |
| Race (NIH/OMB)(Participants) | Pioglitazone Hydrochloride | Normal Standard Care | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 8 | 4 | 12 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Pioglitazone Hydrochloride | Normal Standard Care | Total |
|---|---|---|---|
| United States | 8 | 4 | 12 |
This study is completed, as verified in Aug 2020. You cannot join it, but the record below documents what was studied.
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Children's Hospital Medical Center, Cincinnati