Efficacy & Safety of Resatorvid in Adults With Severe Sepsis
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|ClinicalTrials.gov Identifier: NCT00143611|
Recruitment Status : Completed
First Posted : September 2, 2005
Last Update Posted : February 2, 2012
|Condition or disease||Intervention/treatment||Phase|
|Sepsis||Drug: Resatorvid Drug: Placebo||Phase 3|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||277 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Primary Completion Date :||February 2007|
|Actual Study Completion Date :||February 2007|
|Experimental: Resatorvid 1.2 mg/kg/day||
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||
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||
Resatorvid placebo-matching injection, subcutaneously for thirty minutes; then resatorvid placebo-matching injection, subcutaneously over 96 hours.
- 28-day All-cause Mortality. [ Time Frame: Day 28 ]
- Change from Baseline in Organ Failure Assessment [ Time Frame: Day 28 ]
- Mean Systemic Inflammatory Response [ Time Frame: Day 28 ]
- Mean Vasopressor-free days [ Time Frame: Day 28 ]
- Mean Ventilator-free days [ Time Frame: Day 28 ]
- Mean Intensive Care Unit free days [ Time Frame: Day 28 ]
- Mean Discharge Status. [ Time Frame: Day 28 ]
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
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|Study Director:||VP Clinical Science||Takeda|