Estudio aleatorizado, en doble ciego y controlado con placebo, de la eficacia y la seguridad de TAK-242 frente al placebo en sujetos con insuficiencia cardiovascular y respiratoria inducida por sepsisA Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety ofTAK-242 Versus Placebo in Subjects With Sepsis Induced Cardiovascular and Respiratory Failure
- Conditions
- MedDRA version: 9.1Level: PTClassification code 10040070Term: Septic shockShock séptico e insuficiencia respiratoriaSeptic shock and respiratory failure.MedDRA version: 9.1Level: PTClassification code 10038695Term: Respiratory failure
- Registration Number
- EUCTR2007-005687-27-ES
- Lead Sponsor
- Takeda Global Research & Development Centre (Europe), Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2500
1. The subject is aged 18 years or older.
2. The subject has a suspected or proven bacterial or fungal infection for which he or she is receiving parenteral antimicrobial therapy.
3. The subject has developed at least 3 of the 4 following SIRS criteria within 36 hours prior to start of study drug administration:
a. A temperature from any site >38°C (>100.4°F) or a core temperature (ie, rectal or central) <36°C (<96.8°F).
b. Heart rate of >90 beats per minute. If subject has a known medical condition (eg, heart block) or is receiving treatment (eg, beta blocker) that would prevent tachycardia, only 2 of the remaining 3 criteria for SIRS must be met.
c. Respiratory rate of >20 breaths/min or arterial partial pressure of carbon dioxide of <32 mm Hg or mechanical ventilation for an acute process.
d. A total white blood cell (WBC) absolute count >12,000 cells/mm3 or <4,000 cells/mm3; or a WBC differential count showing >10% immature (band) forms.
4. The subject has septic shock diagnosed within 36 hours prior to study drug administration. Septic shock is defined as hypotension with a persistent requirement for vasopressors to maintain systolic blood pressure >90 mm Hg or mean arterial pressure (MAP) >60 mm Hg, despite adequate fluid resuscitation (eg, >20 mL/kg) or documentation of a central venous pressure >8 mm Hg or a pulmonary artery occlusion pressure >12 mm Hg. Vasopressor is defined as >5 µg/kg/min dopamine or any dose of norepinephrine, epinephrine, vasopressin, or phenylephrine.
5. The subject has developed respiratory failure within 36 hours prior to study drug
administration. Respiratory failure is defined as a ratio of partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FIO2) of <200 while receiving positive pressure ventilation via tracheal tube.
6. The central trial coordinating center, VCC, has approved subject eligibility.
7. The subject or the subjects legally authorized representative has provided written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. The subject has received any investigational compound within 30 days (or 5 half-lives of the drug, whichever is longer) prior to the initiation of the study drug infusion or is participating in another investigational study, not including investigational compound, without prior approval from the VCC/sponsor.
2. The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee, involved in conduct of this study.
3. A female subject who is pregnant or nursing.
4. The subject is currently receiving any immunosuppressive therapy (excluding glucocorticoids) such as methotrexate, azathioprine, anti tumor necrosis factor a (TNF-a), or a cancer related chemotherapeutic agent.
5. The subject has a known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
6. The subject has a methemoglobin level of =5% at pretreatment period or has a known history of methemoglobinemia.
7. The subject is moribund and death is considered imminent.
8. Prior to the onset of sepsis, the subject would not otherwise have been expected to survive 28 days or to complete a functional recovery due to a pre-existing unstable medical condition (eg, a recent acute cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction, severe traumatic injury).
9. The subject has a poorly controlled or metastatic neoplasm.
10. The subject, family, or physician is not committed to full aggressive management or the presence of an unstable medical condition makes the receipt of full aggressive management support unlikely in the view of the coordinating center. The presence of a do not resuscitate order does not automatically exclude participation.
11. The subject has severe end stage chronic respiratory failure or lung disease that significantly impairs physical functioning equivalent to that of New York Heart Association (NYHA) functional classification III or IV.
12. The subject has a documented history of moderate to severe chronic heart failure as defined by NYHA functional classification III or IV.
13. The subject has received electrocardioversion for a pulse-less rhythm or chest compressions during their current hospitalization.
14. The subject is known to be immunocompromised such as subjects with human immunodeficiency virus and a CD4 count <50 mm3, primary immune deficiency or chronic lymphocytic leukemia.
15. The subject has chronic end stage hepatic failure or significant sequelae of chronic hepatic failure (eg, esophageal varices, jaundice, chronic ascites) or Child-Pugh hepatic impairment Classification C.
16. The subject is in a chronic vegetative state or has a similar long-term neurological impairment, where continued aggressive care would be unlikely.
17. The subject has acute third degree burns involving more than 30% of body surface area within 120 hours of first qualifying organ failure.
18. The subject has known hypersensitivity to sulphonamides.
19. The subject has known hypersensitivity to components of TAK-242; for example, is allergic to eggs, egg products, or soybeans.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to evaluate the effects of TAK-242 on all-cause mortality as compared to placebo during the 28-day period from the start of study drug administration.;Secondary Objective: The secondary objectives include an evaluation of the safety profile of TAK-242 vs. placebo, evaluation of the effects of TAK-242 vs. placebo in vasopressor free days, ventilator free days, and ICU free days.;Primary end point(s): The primary efficacy endpoint will be 28-day all-cause mortality. <br>
- Secondary Outcome Measures
Name Time Method