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SepsisPhase 3NCT00143611

Efficacy & Safety of Resatorvid in Adults With Severe Sepsis

A Phase 3 study testing Resatorvid in people with Sepsis, run by Takeda at 144 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis
What is being tested?
Resatorvid
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
277 participants
Where
144 sitesin 17 countries
Study dates
Sep 2005to Feb 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 18Show fewer
  • 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.

Trial locations and contacts

144 sites in 17 countries.

144 sites in 17 countries

United States49 sites

  • Study site

    Akron, Ohio

  • Study site

    Atlanta, Georgia

  • Study site

    Atlantis, Florida

  • Study site

    Augusta, Georgia

  • Study site

    Baltimore, Maryland

  • Study site

    Bay Pines, Florida

  • Study site

    Bellevue, Washington

  • Study site

    Birmingham, Alabama

  • Study site

    Buffalo, New York

  • Study site

    Butte, Montana

  • Study site

    Chicago, Illinois

  • Study site

    Colorado Springs, Colorado

  • Study site

    Columbus, Ohio

  • Study site

    Des Moines, Iowa

  • Study site

    Englewood, New Jersey

  • Study site

    Escondido, California

  • Study site

    Fort Worth, Texas

  • Study site

    Galveston, Texas

  • Study site

    Greensboro, North Carolina

  • Study site

    Greenville, South Carolina

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Jacksonville, Florida

  • Study site

    Kalamazoo, Michigan

  • Study site

    Kansas City, Missouri

  • Study site

    Los Angeles, California

  • Study site

    Louisville, Kentucky

  • Study site

    Lubbock, Texas

  • Study site

    Miami, Florida

  • Study site

    Mobile, Alabama

  • Study site

    Nashville, Tennessee

  • Study site

    New Haven, Connecticut

  • Study site

    New York, New York

  • Study site

    Newark, Delaware

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Orange, California

  • Study site

    Orlando, Florida

  • Study site

    Peoria, Illinois

  • Study site

    Phoenix, Arizona

  • Study site

    Portland, Maine

  • Study site

    Poway, California

  • Study site

    Rochester, New York

  • Study site

    San Diego, California

  • Study site

    Sarasota, Florida

  • Study site

    Scottsdale, Arizona

  • Study site

    Shreveport, Louisiana

  • Study site

    Springfield, Massachusetts

  • Study site

    St Louis, Missouri

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Japan11 sites

  • Study site

    Chiba

  • Study site

    Fukuoka

  • Study site

    Hiroshima

  • Study site

    Hokkaido

  • Study site

    Kumamoto

  • Study site

    Kyoto

  • Study site

    Numakunai

  • Study site

    Osaka

  • Study site

    Shizuoka

  • Study site

    Tokyo

  • Study site

    Yamaguchi

Other trials in Japan

Finland9 sites

  • Study site

    Helsinki

  • Study site

    Joensuu

  • Study site

    Kokkola

  • Study site

    Kuopio

  • Study site

    Lappeenranta

  • Study site

    Oulu

  • Study site

    Seinäjoki

  • Study site

    Tampere

  • Study site

    Turku

Other trials in Finland

Germany9 sites

  • Study site

    Berlin

  • Study site

    Dresden

  • Study site

    Erfurt

  • Study site

    Jena

  • Study site

    Krefeld

  • Study site

    Ludwigshafen

  • Study site

    Mannheim

  • Study site

    München

  • Study site

    Wuppertal

Other trials in Germany

Belgium8 sites

  • Study site

    Aalst

  • Study site

    Antwerp

  • Study site

    Brussels

  • Study site

    Genk

  • Study site

    Ghent

  • Study site

    Liège

  • Study site

    Ottignies

  • Study site

    Yvoir

Other trials in Belgium

Israel8 sites

  • Study site

    Afula

  • Study site

    Ashkelon

  • Study site

    Haifa

  • Study site

    Holon

  • Study site

    Jerusalem

  • Study site

    Kfar Saba

  • Study site

    Petah Tikva

  • Study site

    Tsrifin

Other trials in Israel

Sweden8 sites

  • Study site

    Gävle

  • Study site

    Gothenburg

  • Study site

    Karlstad

  • Study site

    Kristianstad

  • Study site

    Linköping

  • Study site

    Lund

  • Study site

    Stockholm

  • Study site

    Uppsala

Other trials in Sweden

Netherlands7 sites

  • Study site

    's-Hertogenbosch

  • Study site

    Apeldoorn

  • Study site

    Groningen

  • Study site

    Leeuwarden

  • Study site

    Nijmegen

  • Study site

    Rotterdam

  • Study site

    Tilburg

Other trials in Netherlands

Canada6 sites

  • Study site

    Calgary, Alberta

  • Study site

    Halifax, Nova Scotia

  • Study site

    London, Ontario

  • Study site

    Vancouver, British Columbia

  • Study site

    Victoria, British Columbia

  • Study site

    Winnipeg, Manitoba

Other trials in Canada

Czechia6 sites

  • Study site

    Brno

  • Study site

    Havlíčkův Brod

  • Study site

    Hradec Králové

  • Study site

    Opava

  • Study site

    Pilsen

  • Study site

    Prague

Other trials in Czechia

Spain5 sites

  • Study site

    Barcelona

  • Study site

    Getafe

  • Study site

    Madrid

  • Study site

    Valladolid

  • Study site

    Vitoria-Gasteiz

Other trials in Spain

United Kingdom5 sites

  • Study site

    Brighton

  • Study site

    Glasgow

  • Study site

    Leeds

  • Study site

    Livingston

  • Study site

    London

Other trials in United Kingdom

New Zealand4 sites

  • Study site

    Auckland

  • Study site

    Christchurch

  • Study site

    Hastings

  • Study site

    Tauranga

Other trials in New Zealand

Australia3 sites

  • Study site

    Adelaide

  • Study site

    Fremantle

  • Study site

    Heidelberg

Other trials in Australia

Italy3 sites

  • Study site

    Lecco

  • Study site

    Monza

  • Study site

    Pavia

Other trials in Italy

Austria2 sites

  • Study site

    Linz

  • Study site

    Vienna

Other trials in Austria

Puerto Rico1 site

  • Study site

    San Juan

Other trials in Puerto Rico

About this study

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

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.

Read the 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.

Conditions
Sepsis
Being tested
Resatorvid, Placebo
Keywords
Shock, Septic, Sepsis Syndrome, Respiratory Insufficiency, SIRS (Systemic Inflammatory Response Syndrome), Respiratory Failure, Drug Therapy
Medical subject headings
Sepsis, Shock, Septic, Systemic Inflammatory Response Syndrome, Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ResatorvidDrug

    Also called TAK-242

    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.

  • ResatorvidDrug

    Also called TAK-242

    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.

  • PlaceboDrug

    Resatorvid placebo-matching injection, subcutaneously for thirty minutes; then resatorvid placebo-matching injection, subcutaneously over 96 hours.

Study groups in NCT00143611
Study groupRoleWhat they receive
Resatorvid 1.2 mg/kg/dayExperimentalNot described
Receives: Drug: Resatorvid
Resatorvid 2.4 mg/kg/dayExperimentalNot described
Receives: Drug: Resatorvid
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 28-day All-cause Mortality.

    Measured: Day 28

Secondary outcomes (6)

  1. Change from Baseline in Organ Failure Assessment

    Measured: Day 28

  2. Mean Systemic Inflammatory Response

    Measured: Day 28

  3. Mean Vasopressor-free days

    Measured: Day 28

  4. Mean Ventilator-free days

    Measured: Day 28

  5. Mean Intensive Care Unit free days

    Measured: Day 28

  6. Mean Discharge Status.

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2005 (estimated)
  2. Study startSep 2005
  3. Primary completionFeb 2007
  4. Study completionFeb 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
277 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00143611
Sponsor's protocol ID
01-04-TL-242-011
Other IDs
2005-003561-16, U1111-1127-5919, DOH-27-0406-1213, 2005
Status last verified
Jan 2012
First submitted
31 Aug 2005
Last updated
2 Feb 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Rice TW, Wheeler AP, Bernard GR, Vincent JL, Angus DC, Aikawa N, Demeyer I, Sainati S, Amlot N, Cao C, Ii M, Matsuda H, Mouri K, Cohen J. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med. 2010 Aug;38(8):1685-94. doi: 10.1097/CCM.0b013e3181e7c5c9.

    PubMed 20562702

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Resatorvid in people with Sepsis, run by Takeda at 144 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 144 sites in United States, Japan, Finland, Germany, Belgium and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

28-day All-cause Mortality. (time frame: Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00143611, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2012.

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