A Study To Evaluate Efficacy & Safety Of TAK-242 In Adults With Severe Sepsis

This drug is being developed to treat severe sepsis with septic shock and/or respiratory failure. The primary purpose of this study is to identify the optimal dosing regimen and to demonstrate that TAK-242 reduces 28-day all-cause mortality in subject with severe sepsis.

Official Title

A Pivotal, Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety of TAK-242 in Adults With Severe Sepsis

Conditions

• Sepsis
• Shock, Septic;
• Sepsis Syndrome
• Respiratory Insufficiency

Study Type

Interventional

Study Design

Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Further Details

• Primary Outcomes: 28-day all-cause mortality

Study Start

August 2005

Eligibility & Criteria

• Ages Eligible for Study: 18 Years and above
• Genders Eligible for Study: Both

Inclusion Criteria:

• Clinical evidence of infection
• Subject must meet at least 3 of the following 4 criteria for systemic inflammatory response syndrome: a) core temperature of >38C (>100.4F) or <36C (<96.8F), b) heart rate of >90 beats per minute, c) Respiratory rate of >20 breaths/min or PaCO2 of <32 mmHg requiring mechanical ventilation or d) 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.
• Subject must have sepsis with shock and/or respiratory failure with onset manifesting less than or equal to 36 hours before the initiation of study drug infusion.

Exclusion Criteria:

• Subject is less than 18 years of age
• If female, the subject is pregnant or nursing
• Subject is receiving immunosuppressive therapy such as cyclosporine, azothioprine, or cancer-related chemotherapy
• Subject has a granulocyte count of less than 1000/mm3 except if the decreased count is believed to be due to sepsis
• Subject has documented or suspected acute myocardial infarction within the last 6 weeks prior to Pretreatment Period
• Subject has a documented history of moderate to severe chronic heart failure as defined by New York Heart Association (NYHA) Functional Classification III or IV
• Subject is known to be HIV positive with known CD4 count less than or equal to 50/mm3 or has known end-stage processes (eg, progressive multifocal leukoencephalopathy, systemic mycobacterium avium complex infection)
• Subject has known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Subject has methemoglobin level of >5% at Pretreatment Period or has known history of methemoglobinemia
• Subject is moribund and death is considered imminent
• Subject is classified as “Do Not Resuscitate” (DNR) or “Do Not Treat” or the subject family has not committed to aggressive management of the subject condition
• Subject is not expected to survive for 28 days and will not likely be given life support due to a pre-existing, uncorrectable medical condition
• Subject has known esophageal varices, chronic jaundice, cirrhosis, or chronic ascites
• Subject is in a chronic vegetative state or has a similar long-term neurological condition
• Subject has known portal hypertension or Child-Pugh hepatic impairment class C
• Subject has had acute third degree burns involving more than 30% of body surface within 120 hours prior to Pretreatment Period
• Subject has known hypersensitivity to sulfonamides
• Subject has known hypersensitivity to components of TAK-242; ie, is allergic to eggs, egg products, or soybeans
• Subject has participated in any other investigational study within 30 days or 5 half-lives of the drug

Total Enrolment

2930 (expected)

Contact Details

• Adelaide, Australia; Recruiting
• Heidelberg, Australia; Recruiting
• Fremantle, Australia; Recruiting