We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Efficacy & Safety of Resatorvid in Adults With Severe Sepsis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00143611
Recruitment Status : Completed
First Posted : September 2, 2005
Last Update Posted : February 2, 2012
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to determine the optimal dose of Resatorvid for reducing 28-day all-cause mortality in subjects with severe sepsis.

Condition or disease Intervention/treatment Phase
Sepsis Drug: Resatorvid Drug: Placebo Phase 3

Detailed Description:

Severe sepsis, defined as sepsis associated with acute organ dysfunction, remains a serious medical problem worldwide. In the United States alone, approximately 750,000 cases of severe sepsis occur each year, with the mortality rate ranging between 30% and 50% for severe sepsis patients with concomitant organ dysfunction. As the population ages, these numbers are expected to increase. The pathophysiology of severe sepsis is thought to involve the activation of a variety of inflammatory and procoagulant host responses to infection, which if unchecked, can lead to diffuse endovascular injury, multi-organ dysfunction, and ultimately death.

The host response to infection with microorganism and microorganism-derived molecules is characterized by the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins 1, 6 and 8 (IL-1, IL-6, and IL-8), by inflammatory cells, and by other markers of inflammation such as C-reactive protein. Inflammatory cells, such as macrophages, release these cytokines by signals transmitted from the surface of these cells after binding of pathogen-associated molecules to cell surface pattern recognition receptors known as toll-like receptors.

TAK-242 (resatorvid) is a small molecule suppressor of pathogen-induced release of inflammatory cytokines and acts by inhibiting TLR-4 mediated signaling. Because of its inhibitory effect on suppressing cytokine levels, resatorvid is being developed as a treatment for severe sepsis.

The study was ended after the DSMB determined there was insufficient cytokine suppression in the 150-subject analysis within Stage 1 of the study.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 277 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : September 2005
Primary Completion Date : February 2007
Study Completion Date : February 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Resatorvid 1.2 mg/kg/day Drug: Resatorvid
Resatorvid 1.2 mg/kg, injection, subcutaneously for thirty minutes; then resatorvid 0.05 mg/kg/h (1.2 mg/kg/day), injection, subcutaneously over 96 hours.
Other Name: TAK-242
Experimental: Resatorvid 2.4 mg/kg/day Drug: Resatorvid
Resatorvid 1.2 mg/kg, injection, subcutaneously for thirty minutes; then resatorvid 0.1 mg/kg/h (2.4 mg/kg/day), injection, subcutaneously over 96 hours.
Other Name: TAK-242
Placebo Comparator: Placebo Drug: Placebo
Resatorvid placebo-matching injection, subcutaneously for thirty minutes; then resatorvid placebo-matching injection, subcutaneously over 96 hours.

Outcome Measures

Primary Outcome Measures :
  1. 28-day All-cause Mortality. [ Time Frame: Day 28 ]

Secondary Outcome Measures :
  1. Change from Baseline in Organ Failure Assessment [ Time Frame: Day 28 ]
  2. Mean Systemic Inflammatory Response [ Time Frame: Day 28 ]
  3. Mean Vasopressor-free days [ Time Frame: Day 28 ]
  4. Mean Ventilator-free days [ Time Frame: Day 28 ]
  5. Mean Intensive Care Unit free days [ Time Frame: Day 28 ]
  6. Mean Discharge Status. [ Time Frame: Day 28 ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Has clinical evidence of infection defined as the presence of a known or probable source of infection requiring the initiation of parenteral antimicrobial therapy.
  • Must meet at least 3 of the following 4 criteria for SIRS:

    • A core temperature greater than 38°C or less than 36°C.
    • A heart rate greater than 90 beats per minute.
    • A respiratory rate greater than 20 breaths/min or partial pressure of carbon dioxide in arterial blood less than 32 mm Hg or mechanical ventilation for an acute process.
    • A total white blood cell absolute count greater than 12,000 cells/mm3 or less than 4,000 cells/mm3, or a white blood cell differential count that showed greater than 10% immature (band) forms.
  • Must have sepsis with shock and/or respiratory failure.

Exclusion Criteria

  • If female, the subject is pregnant, nursing and the milk is intended to be ingested by the infant, or the participant plans to become pregnant, or nurse and the milk is intended to be ingested by the infant.
  • Is receiving immunosuppressive therapy such as cyclosporine, azathioprine, or cancer-related chemotherapy.
  • Has a granulocyte count of less than 1000/mm3 except if the decreased count was believed to be due to sepsis.
  • Has documented or suspected acute myocardial infarction within the last 6 weeks prior to Pretreatment Period.
  • Has a documented history of moderate to severe chronic heart failure as defined by New York Heart Association Functional Classification III or IV.
  • Is known to be positive for human immunodeficiency virus with known CD4 count less than or equal to 50/mm3 or had known end-stage processes.
  • Has a known history of glucose-6-phosphate dehydrogenase deficiency.
  • Has a methemoglobin level greater than 5% at Pretreatment Period or had a known history of methemoglobinemia.
  • Is moribund and death was considered imminent.
  • Is classified as "Do Not Resuscitate", or "Do Not Treat", or the participant's family has not committed to aggressive management of the participant's condition.
  • Is not expected to survive for 28 days and was not likely be given life support due to a pre-existing, uncorrectable medical condition.
  • Has a known esophageal varices, chronic jaundice, cirrhosis, or chronic ascites.
  • Is in a chronic vegetative state or has a similar long-term neurological condition.
  • Has known portal hypertension or Child-Pugh hepatic impairment class C.
  • Has acute third degree burns involving more than 30% of body surface within 120 hours prior to Pretreatment Period.
  • Has known hypersensitivity to sulfonamides.
  • Has known hypersensitivity to components of resatorvid.
  • Has participated in any other investigational study (drug or device) and/or taken any investigational drug within 30 days or 5 half-lives of the drug.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00143611

  Hide Study Locations
United States, Alabama
Birmingham, Alabama, United States
Mobile, Alabama, United States
United States, Arizona
Phoenix, Arizona, United States
Scottsdale, Arizona, United States
United States, California
Escondido, California, United States
Los Angeles, California, United States
Orange, California, United States
Poway, California, United States
San Diego, California, United States
United States, Colorado
Colorado Springs, Colorado, United States
United States, Connecticut
New Haven, Connecticut, United States
United States, Delaware
Newark, Delaware, United States
United States, Florida
Atlantis, Florida, United States
Bay Pines, Florida, United States
Jacksonville, Florida, United States
Miami, Florida, United States
Orlando, Florida, United States
Sarasota, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Augusta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
Peoria, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Iowa
Des Moines, Iowa, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Louisiana
Shreveport, Louisiana, United States
United States, Maine
Portland, Maine, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Springfield, Massachusetts, United States
United States, Michigan
Kalamazoo, Michigan, United States
United States, Missouri
Kansas City, Missouri, United States
St. Louis, Missouri, United States
United States, Montana
Butte, Montana, United States
United States, New Jersey
Englewood, New Jersey, United States
United States, New York
Buffalo, New York, United States
New York, New York, United States
Rochester, New York, United States
United States, North Carolina
Greensboro, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Akron, Ohio, United States
Columbus, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, South Carolina
Greenville, South Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Fort Worth, Texas, United States
Galveston, Texas, United States
Houston, Texas, United States
Lubbock, Texas, United States
United States, Washington
Bellevue, Washington, United States
Adelaide, Australia
Fremantle, Australia
Heidelberg, Australia
Linz, Austria
Wien, Austria
Aalst, Belgium
Antwerpen, Belgium
Brussel, Belgium
Bruxelles, Belgium
Genk, Belgium
Gent, Belgium
Liege, Belgium
Ottignies, Belgium
Yvoir, Belgium
Canada, Alberta
Calgary, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Victoria, British Columbia, Canada
Canada, Manitoba
Winnipeg, Manitoba, Canada
Canada, Nova Scotia
Halifax, Nova Scotia, Canada
Canada, Ontario
London, Ontario, Canada
Czech Republic
Brno, Czech Republic
Havlickuv Brod, Czech Republic
Hradec Kralove, Czech Republic
Opava, Czech Republic
Pilsen, Czech Republic
Prague, Czech Republic
Helsinki, Finland
Joensuu, Finland
Kokkola, Finland
Kuopio, Finland
Lappeenranta, Finland
Oulu, Finland
Seinajoki, Finland
Tampere, Finland
Turku, Finland
Berlin, Germany
Dresden, Germany
Erfurt, Germany
Jena, Germany
Krefeld, Germany
Ludwigshafen, Germany
Mannheim, Germany
Munchen, Germany
Wuppertal, Germany
Afula, Israel
Ashkelon, Israel
Haifa, Israel
Holon, Israel
Jerusalem, Israel
Kfar Saba, Israel
Petach-Tikva, Israel
Zerifin, Israel
Lecco, Italy
Monza, Italy
Pavia, Italy
Chiba, Japan
Fukuoka, Japan
Hiroshima, Japan
Hokkaido, Japan
Iwate, Japan
Kumamoto, Japan
Kyoto, Japan
Osaka, Japan
Shizuoka, Japan
Tokyo, Japan
Yamaguchi, Japan
Apeldoorn, Netherlands
Groningen, Netherlands
Leeuwarden, Netherlands
Nijmegen, Netherlands
Rotterdam, Netherlands
s-Hertogenbosch, Netherlands
Tilburg, Netherlands
New Zealand
Auckland, New Zealand
Christchurch, New Zealand
Hastings, New Zealand
Tauranga, New Zealand
Puerto Rico
San Juan, Puerto Rico
Barcelona, Spain
Getafe, Spain
Madrid, Spain
Valladolid, Spain
Vitoria, Spain
Gavle, Sweden
Goteborg, Sweden
Karlstad, Sweden
Kristianstad, Sweden
Linkoping, Sweden
Lund, Sweden
Stockholm, Sweden
Uppsala, Sweden
United Kingdom
Brighton, United Kingdom
Glasgow, United Kingdom
Leeds, United Kingdom
Livingston, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Study Director: VP Clinical Science Takeda
More Information

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00143611     History of Changes
Other Study ID Numbers: 01-04-TL-242-011
2005-003561-16 ( EudraCT Number )
U1111-1127-5919 ( Registry Identifier: WHO )
DOH-27-0406-1213 ( Registry Identifier: SANCTR )
First Posted: September 2, 2005    Key Record Dates
Last Update Posted: February 2, 2012
Last Verified: January 2012

Keywords provided by Takeda:
Shock, Septic
Sepsis Syndrome
Respiratory Insufficiency
SIRS (Systemic Inflammatory Response Syndrome)
Respiratory Failure
Drug Therapy

Additional relevant MeSH terms:
Systemic Inflammatory Response Syndrome
Pathologic Processes