SepsisPhase 3NCT00633477
Efficacy and Safety of Resatorvid in Patients With Sepsis-induced Cardiovascular and Respiratory Failure
A Phase 3 study testing Resatorvid in people with Sepsis, run by Takeda at 1 site in Japan.
Trial summary
The purpose of this study is to determine the effect of resatorvid on subjects with 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
- 18 participants
- Where
- 1 siteJapan
- Study dates
- Feb 2008to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Suspected or proven bacterial or fungal infection for which patient is receiving parenteral antimicrobial therapy.
- Developed at least 3 of the 4 following systemic inflammatory response syndrome criteria within 36 hours prior to start of study drug administration:
- A temperature from any site greater than 38°C (greater than 100.4°F) or a core temperature less than 36°C (less than 96.8°F).
- Heart rate of greater than 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 systemic inflammatory response syndrome must be met.
- Respiratory rate of greater than 20 breaths per min or arterial partial pressure of carbon dioxide of less than 32 mm Hg or mechanical ventilation for an acute process.
- A total white blood cell absolute count greater than 12,000 cells per mm3 or less than 4,000 cells/mm3; or a white blood cell differential count showing greater than 10% immature (band) forms.
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- Has septic shock diagnosed within 36 hours prior to study drug administration..
- Has developed respiratory failure within 36 hours prior to study drug administration.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Who cannot join
- 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 Vanderbilt Coordinating Center or the sponsor.
- Currently receiving any immunosuppressive therapy (excluding glucocorticoids) such as methotrexate, azathioprine, anti tumor necrosis factor alpha, or a cancer related chemotherapeutic agent.
- Known history of glucose-6-phosphate dehydrogenase deficiency.
- Methemoglobin level of greater than or equal to 5% at pretreatment period or has a known history of methemoglobinemia.
- Moribund and death is considered imminent.
- 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).
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- Poorly controlled or metastatic neoplasm.
- The participant, the participant's 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.
- Severe end stage chronic respiratory failure or lung disease that significantly impairs physical functioning equivalent to that of New York Heart Association functional classification III or IV.
- Documented history of moderate to severe chronic heart failure as defined by New York Heart Association functional classification III or IV.
- Received electrocardioversion for a pulse-less rhythm or chest compressions during their current hospitalization.
- Known to be immunocompromised such as subjects with human immunodeficiency virus and a CD4 count less than 50 mm3, primary immune deficiency or chronic lymphocytic leukemia.
- 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.
- In a chronic vegetative state or has a similar long-term neurological impairment, where continued aggressive care would be unlikely.
- Acute third degree burns involving more than 30% of body surface area within 120 hours of first qualifying organ failure.
- Known hypersensitivity to sulphonamides.
- Known hypersensitivity to components of resatorvid; for example, is allergic to eggs, egg products, or soybeans.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of TAK-242 Versus Placebo in Subjects With Sepsis-Induced Cardiovascular and Respiratory Failure
The purpose of this study is to determine the effect of resatorvid on subjects with sepsis.
Read the detailed description
Sepsis is a major cause of in-hospital death, with a higher mortality rate than events such as stroke and acute myocardial infarction, each with less than a 20% risk of death in the first 30 days. Sepsis is a clinical condition caused by the innate inflammatory host response to systemic infection that can result in organ failure and potentially death. Under certain circumstances, many components of the innate immune response that are normally involved with host defense can cause cell and tissue damage and subsequently multiple organ failure, the clinical hallmark of severe sepsis.
The host response to infection is characterized by the synthesis and release of proinflammatory cytokines. Cytokines are released by signals transmitted from the surface of inflammatory cells, after binding of pathogen-associated molecules to cell surface pattern recognition receptors known as toll-like receptors.
TAK-242 (resatorvid) is a toll-like receptor 4 inhibitor under clinical development for the treatment of patients with severe sepsis. Study participation is anticipated to be about 28 days, with an additional 9 month follow-up period.
- Conditions
- Sepsis
- Being tested
- Resatorvid, Placebo
- Keywords
- Systemic Inflammatory Response Syndrome, Septic Shock, Septicemia, Drug Therapy
- Medical subject headings
- Sepsis, Systemic Inflammatory Response Syndrome, Shock, Septic
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 emulsion, injection for 30 minutes and resatorvid 2.4 mg/kg per-day emulsion, injection, continuous infusion for 96 hours.
PlaceboDrug
Resatorvid placebo-matching emulsion, injection for 30 minutes and resatorvid placebo-matching emulsion, injection, continuous infusion for 96 hours.
| Study group | Role | What they receive |
|---|---|---|
| Resatorvid 2.4 mg/kg/day | Experimental | Not described Receives: Drug: Resatorvid |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause Mortality
Mortality regardless of cause at Day 28
Measured: Day 28
Secondary outcomes (3)
ICU Free Days
Number days participant was not in ICU
Measured: Day 28
Vasopressor Free Days.
Number days participant did not need vasopressors.
Measured: Day 28
Ventilator Free Days.
Number days participant was not on Ventilattor support.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: Business Decision; No Safety Or Efficacy Concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00633477
- Sponsor's protocol ID
- TAK-242_301
- Other IDs
- 2007-005687-27, U1111-1127-6016
- Status last verified
- Jan 2013
- First submitted
- 4 Mar 2008
- Last updated
- 18 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of TAK-242 Versus Placebo in Subjects With Sepsis-Induced Cardiovascular and Respiratory Failure
- ClinicalTrials.gov ID
- NCT00633477
- Acronym / sponsor ID
- TAK-242_301
- Conditions
- Sepsis
- Keywords
- Systemic Inflammatory Response Syndrome, Septic Shock, Septicemia, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision; No Safety Or Efficacy Concerns.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 12 Mar 2008 (estimated)
- Results
- Posted 9 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effect of resatorvid on subjects with sepsis.
Detailed description
Sepsis is a major cause of in-hospital death, with a higher mortality rate than events such as stroke and acute myocardial infarction, each with less than a 20% risk of death in the first 30 days. Sepsis is a clinical condition caused by the innate inflammatory host response to systemic infection that can result in organ failure and potentially death. Under certain circumstances, many components of the innate immune response that are normally involved with host defense can cause cell and tissue damage and subsequently multiple organ failure, the clinical hallmark of severe sepsis.
The host response to infection is characterized by the synthesis and release of proinflammatory cytokines. Cytokines are released by signals transmitted from the surface of inflammatory cells, after binding of pathogen-associated molecules to cell surface pattern recognition receptors known as toll-like receptors.
TAK-242 (resatorvid) is a toll-like receptor 4 inhibitor under clinical development for the treatment of patients with severe sepsis. Study participation is anticipated to be about 28 days, with an additional 9 month follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Resatorvid 2.4 mg/kg/day | Experimental | Drug: Resatorvid |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Suspected or proven bacterial or fungal infection for which patient is receiving parenteral antimicrobial therapy.
- Developed at least 3 of the 4 following systemic inflammatory response syndrome criteria within 36 hours prior to start of study drug administration:
- Has septic shock diagnosed within 36 hours prior to study drug administration..
- Has developed respiratory failure within 36 hours prior to study drug administration.
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
Key exclusion criteria (17 listed)
- 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 Vanderbilt Coordinating Center or the sponsor.
- Currently receiving any immunosuppressive therapy (excluding glucocorticoids) such as methotrexate, azathioprine, anti tumor necrosis factor alpha, or a cancer related chemotherapeutic agent.
- Known history of glucose-6-phosphate dehydrogenase deficiency.
- Methemoglobin level of greater than or equal to 5% at pretreatment period or has a known history of methemoglobinemia.
- Moribund and death is considered imminent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ResatorvidAlso: TAK-242Resatorvid 1.2 mg/kg emulsion, injection for 30 minutes and resatorvid 2.4 mg/kg per-day emulsion, injection, continuous infusion for 96 hours. | Drug | Resatorvid 2.4 mg/kg/day |
| PlaceboResatorvid placebo-matching emulsion, injection for 30 minutes and resatorvid placebo-matching emulsion, injection, continuous infusion for 96 hours. | Drug | Placebo |
Primary outcome
All-cause Mortality
Time frame: Day 28
Mortality regardless of cause at Day 28
3 secondary outcomes
ICU Free Days
Time frame: Day 28
Vasopressor Free Days.
Time frame: Day 28
Ventilator Free Days.
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
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CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
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Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VP Clinical Science study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Resatorvid in people with Sepsis, run by Takeda at 1 site in Japan.
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 9 inclusion and 17 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: stopped early, as of the sponsor's last update on 18 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. 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?
Yes. Results are posted in the registry (first posted 9 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
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?
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 18 Jan 2013.