None listed
Conditions
Interventions
STAGE 1. GROUP 1 Type of group
This group will be treated with TAK-242 in a loading dose of 1.2 mg / kg / day, IV, for 30 minutes. Subsequently, TAK-242 will continue at a dose of 0.05 mg / kg / day, IV, in continuous infusion for 96 hours.
Group name:PHASE 2. GROUP 2 Type of group
This group will be treated with TAK-242 at the dose selected as the most effective in stage 1. A bolus of 0.05 mg / kg / hour may be used, followed by an IV infusion of 1.2 mg / kg / day OR a bolus of 0.1 mg / kg / hour, followed by an IV infusion of 2.4 mg / kg / day for 96 hours
Sponsors
TAKEDA GLOBAL RESEARCH & DEVELOPMENT CENTER, INC.,
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Clinical evidence of infection that requires initiation of parenteral antimicrobial therapy. 2. The subject must present at least 3 of the 4 criteria of the systemic inflammatory response syndrome (SIRS). 3. The subject must suffer sepsis with septic shock or respiratory failure, or both. The onset of shock or respiratory failure should be manifested within 24 hours before the start of the study drug infusion, which should be done as soon as possible, preferably during the first 24 hours. 4. The subject or his / her authorized legal representative has given a written informed consent, or can orally understand the English language or another language with certified translation of the approved informed consent.
Exclusion criteria
Exclusion criteria: 1. The subject is under 18 years of age. 2. For female subjects, if the patient is pregnant, is breastfeeding or if the patient intends to become pregnant or if she plans to breastfeed. 3. The subject is receiving immunosuppressive therapy. 4. Subject has a granulocyte count less than 1000 / mm3. 5. Subject has documented or suspected acute myocardial infarction within the last 6 weeks prior to the Pretreatment period. 6. The subject has a documented history of moderate to severe chronic heart failure. 7. It is known that the subject is HIV positive with a known CD4 count ≤ 50 / mm3 or is known to have a terminal processes. 8. The subject has a known history of glucose-6-phosphate dehydrogenase deficiency (G6PD). 9. The subject has a methemoglobin level ≥ 5% in the Pretreatment period or has a known history of methemoglobinemia. 10. The subject is dying or death is considered imminent. 11. The subject is classified as Do not resuscitate or Do not treat, or the subject´s family does not agree with an aggressive management to treat the condition of the subject. 12. The subject´s life expectancy is less than 28 days and life support will probably not be given due to a pre-existing medical condition and no cure. 13. The subject has a known condition of esophageal varices, chronic jaundice, cirrhosis, or chronic ascites. 14. The subject is in a chronic vegetative state or has a similar prolonged neurological condition. 15. The subject has a known condition of portal hypertension or Child-Pugh class C hepatic insufficiency. 16. The subject has suffered acute burns of the third degree with a compromise> 30% of the body surface within 120 hours prior to the Pretreatment period. 17. The subject has a known hypersensitivity to sulfonamides. 18. The subject has known hypersensitivity to the components of TAK-242. 19. The subject has participated in any other research study and / or has received any investigational drug within 30 days or 5 half lives of the drug, whichever is longer, before starting the infusion with the study drug. . 20. The subject is not well predisposed, or the subject can not be fully evaluated during the 28-day study period. 21. The subject is an employee of the study center, or is a direct relative of an employee of the study center who is directly involved in conducting the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Clinical evaluation to determine the death of patients within 28 days after starting treatment. Measure:Mortality from any cause after 28 days. Timepoints:28 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Criterion 1: Sequential Evaluation of Organic Insufficiency (ESIO), which is a scale that evaluates the following aspects: Respiratory, coagulation, hepatic, cardiovascular, central nervous system and renal. Criterion 2: Clinical improvement will be evaluated according to the following data: days free of SIRS, vasopressor and ventilator, time in the intensive care unit (UCI) and status of the situation at discharge. Measure:1) Evaluation of organic insufficiency. 2) Clinical improvement. Timepoints:When the event is presented. ; Outcome name:Criterion 1: Evaluation of any unfavorable medical event that occurs during the treatment with the product under investigation. Criterion 2: Panels of hematology and serum chemistry, laboratory analysis. Criterion 3: Weight, mean and systolic blood pressure, heart rate, central temperature and 12-lead electrocardiogram alterations will be evaluated. Criterion 4: Findings in the physical examination and previous and concomitant medications. Measure:Safety of treatment: 1) Adverse events. 2) Clinical laboratory analysis. 3) Weight, vital signs and ECG. 4) Others. Timepoints:Adverse events: Days 1, 2, 3, 4, 5, 7, 14, 21 and 28. Laboratory analysis: Days 1, 2, 3, 4, 7 and 14. ECG, vital signs, physical examination, weight: Before the start of treatment and days 4, 14, 21 and 28. ; Outcome name:1) Pharmacodynamics: Serum levels of IL-6, IL-8, IL-10, Tumor Necrosis Factor (TNF) -a, Procalcitonin (PCT), and C-Reactive Protein (PCR). 2) Pharmacokinetics: Detailed profile of TAK-242, M-I and M-III in patients with sepsis. Measure:Pharmacodynamics and pharmacokinetics. Timepoints:Days 1, 2, 3, 4 and 7. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Finland, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Spain, Sweden, United Kindgdom, United States
Outcome results
None listed