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Sepsis and CoagulopathyPhase 3Scarlet2NCT03517501

The Safety And Efficacy of ART-123 in Subjects With Sepsis and Coagulopathy

A Phase 3 study testing ART-123 in people with Sepsis and Coagulopathy, run by Asahi Kasei Pharma America Corporation.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis and Coagulopathy
What is being tested?
ART-123
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Jul 2019to May 2023
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

  • Subjects must be receiving treatment in an ICU or in an acute care setting (e.g., Emergency Room, Recovery Room).
  • Subjects with either compelling evidence of infection OR clinical syndromes highly likely to be bacterial in origin, as follows (Please refer to Appendix B):
  • Compelling objective evidence of bacterial infection and a known site of infection: Objective evidence would be met with a grossly purulent site of infections, Gram stain evidence, confirming a bacterial pathogen from normally sterile fluids (blood, urine, cerebrospinal fluid (CSF), peritoneal fluid, etc.), having either:
  • White Blood Cell (WBC) count greater > 12,000/mm3 or < 4,000/mm3 or > 10% bands within 36 hours of randomization OR
  • Temperature <36°C or fever >38°C
  • Clinical syndromes highly likely to be bacterial in origin but not compelling
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  • White Blood Cell (WBC) count greater > 12,000/mm3 or < 4,000/mm3 or > 10% bands within 36 hours of randomization AND
  • Temperature <36°C or fever >38°C
  • Current treatment with intravenous antibiotics for the acute bacterial infection (i.e. not prophylactic antibiotics)
  • Subjects with sepsis-associated organ dysfunction defined by at least one of the following:
  • Cardiovascular Dysfunction defined as requiring both adequate fluid resuscitation and vasopressors* to maintain Mean Arterial Pressure (MAP) greater than or equal to (≥) 65 mmHg (implies fluid resuscitation alone does not raise MAP to ≥ 65 mmHg), with onset time being the time of vasopressors are initiated (end of surgery if initiated in surgery), with adequate fluid resuscitation defined as:
  • Intravenous administration of at least 20 mL/kg crystalloid or 10 mL/kg colloid infusion within 6 hours.
  • OR
  • •Central Venous Pressure (CVP) of greater than (>) 8 mmHg or Pulmonary Artery Wedge Pressure (PAWP) of greater than (>) 12 mmHg.
  • If dopamine is the only vasopressor used, the infusion rate must be greater than (>) 5 μg/kg/min (i.e., must be prescribed to support cardio-pulmonary perfusion). If vasopressin is used, it must be given in conjunction with another vasopressor.
  • Respiratory Dysfunction is defined as the acute need for mechanical ventilation and PaO2/FiO2 ratio of <250 (or < 200 when lung is the site of infection) with onset time being time of intubation prior to first qualifying PaO2:FiO2 (if intubated for surgery and unable to extubate the qualifying time is the end of surgery), with mechanical ventilation defined as any type of ventilation administered via an endotracheal or nasotracheal tube.
  • Subjects with coagulopathy characterized by an INR >1.40 without other known etiology (e.g., anticoagulant therapy, chronic liver disease), and having an onset at the time of the first blood draw yielding a qualifying result (point of care device INR results must be confirmed by local laboratory).
  • Subjects with coagulopathy characterized by platelet count that meets any of the below criteria, and having an onset at the time of the first blood draw yielding a qualifying result.
  • ≥ 20,000/mm3 and ≤ 30,000/mm3 that upon retesting after platelet transfusion is > 30,000/mm3 (qualifying at the time of the first blood draw yielding a result ≥ 20,000/mm3 and ≤ 30,000/mm3)
  • > 30,000/mm3 to < 150,000/mm3
  • > 30% decrease in platelet count within 24 hours
  • First and last qualifying criteria of sepsis associated organ dysfunction (as defined in Inclusion #4), platelet count and INR occurring in ≤ 24 hours

Who cannot join

  • Candidates for the study will be excluded if ANY of the following criteria are present:
  • Subject or Authorized Representative is unable or unwilling to provide informed consent (as applicable per local and country regulations)
  • Subject is pregnant (positive serum or urine human Chorionic Gonadotropin (hCG)) or breastfeeding or intends to get pregnant within 28 days of enrolling into the study
  • Subject is < 18 years of age
  • Body weight ≥ 175 kg
  • Subject is unwilling to allow transfusion of blood or blood products
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  • Presence of an advance directive to withhold life-sustaining treatment (except Cardiopulmonary Resuscitation), or likely to have life support withdrawn within 24 hours of consent
  • Subject has had previous treatment with ART-123
  • Platelet count < 20,000/ mm3 for any reason, or for platelet count ≥ 20,000/mm3 and ≤ 30,000/mm3 that upon retesting after platelet transfusion does not increase > 30,000/mm3
  • Elevated INR, leukopenia, or thrombocytopenia that is not due to sepsis, (e.g. patients treated by chemotherapy agent). Please refer to Appendix C as an example of agents known to cause myelosuppression that should be evaluated as the cause of potential leukopenia or thrombocytopenia
  • Inability to randomize patients in ≤ 12 hours after meeting Inclusion # 7 (onset time requirements for sepsis associated organ dysfunction, INR, and platelet count)
  • ≤ 8 hours remaining from the end of a major surgery having a high risk of post-operative bleeding and randomization (e.g. extensive intraabdominal or intrathoracic dissection, debridement of a large surface area of tissue, complications arising during surgery, problems with hemostasis during surgery, surgeries of long duration, surgeries with large estimated blood loss).
  • Ensures all randomized surgical subjects with a high risk of post-operative bleeding can be dosed no earlier than 12 hours post-operatively, as described in Section 2.6.3. (minimum 8 hour delay before randomization and 4 hour maximum time to dose after randomization)
  • Stroke within 3 months prior to consent, trauma or major surgery within 3 months prior to consent that may increase the risk of bleeding
  • Known bleeding diatheses or anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia, esophageal varices, arteriovenous malformation)
  • Gastrointestinal bleeding (e.g., melena, hematemesis) or genitourinary bleeding within 6 weeks prior to consent unless a corrective interventional procedure has been performed (i.e., therapeutic endoscopy), or there is evidence of complete resolution
  • Known thrombophilia or a history of deep-vein thrombosis or pulmonary embolism within 3 months prior to consent
  • Need for full dose anticoagulation therapy (other than IV unfractionated heparin discontinued > 12 hours prior to randomization), full dose or catheter directed thrombolysis, aspirin at a daily dose > 325 mg, long-acting antiplatelet drugs (e.g. clopidogrel, prasugrel, or ticagrelor), dual antiplatelet therapy, and doses of anticoagulants exceeding thromboprophylaxis doses within 72 hours prior to the first dose of study drug (see Appendix D for more detail)
  • Acute liver failure not due to sepsis, sepsis associated acute liver failure in any patient with a history of cirrhosis, Class C Chronic liver disease (Child-Pugh score of 10-15); (See Appendix E)
  • Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture or Gram stain consistent with bacterial infection. Also, in the opinion of the investigator the subject is at increased risk for developing hemorrhagic pancreatitis over the duration of the study
  • Acute renal failure not due to sepsis or chronic renal failure requiring chronic RRT (Renal Replacement Therapy)
  • Imminent death or anticipated life expectancy < 90 days for any reason other than the acute sepsis
  • Participation in another research study involving an investigational agent within 30 days prior to consent, or projected study participation before the Day 29 assessment post randomization
  • Confirmed or suspected endocarditis, malaria, Pneumocystis jiroveci pneumonia, or viral infections associated with hemorrhage (e.g. dengue fever, lassa, ebola, Bolivian) during the current admission

About this study

Official title: Scarlet-2: A Randomized, Double-Blind,Placebo-Controlled, Phase 3 Study to Assess The Safety And Efficacy of ART-123 in Subjects With Sepsis and Coagulopathy

The purpose of the study is to evaluate if ART-123 given to patients who have severe sepsis can decrease mortality.

Read the detailed description

Study is to evaluate if ART-123 given to patients who have severe sepsis complicated by at least one organ dysfunction and coagulopathy can decrease mortality

Being tested
ART-123, Placebo Comparator - Placebo
Medical subject headings
Sepsis, Hemostatic Disorders

What participants receive

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

  • ART-123Drug

    Also called human recombinant thrombomodulin

    Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

  • Placebo Comparator - PlaceboDrug

    Dose: 0.06 mg/kg/day up to a maximum dose of 6 mg/day for 6 days

Study groups in NCT03517501
Study groupRoleWhat they receive
ART-123Active comparatorNot described
Receives: Drug: ART-123
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo Comparator - 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: 28 days

Secondary outcomes (5)

  1. 3 months

    Follow up of all-cause mortality

    Measured: 3 months

  2. Resolution of organ dysfunction through 28 days as measured by:

    Shock free and alive days

    Measured: 28 days

  3. Resolution of organ dysfunction through 28 days as measured by:

    ventilator free and alive days

    Measured: 28 days

  4. Resolution of organ dysfunction through 28 days as measured by:

    dialysis free and alive days

    Measured: 28 days

  5. 6 and 12 months

    Follow-up of all-cause mortality at

    Measured: 6 or 12 months

Timeline

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

  1. First posted7 May 2018
  2. Study startJul 2019 (estimated)
  3. Primary completionApr 2022 (estimated)
  4. Study completionMay 2023 (estimated)

Why it stopped: Sponsor will amend study design by incorporating reconfirmation of coagulopathy following discussion with FDA regarding findings from SCARLET1 study.

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03517501
Sponsor's protocol ID
AKPA 3-3002
Acronym
Scarlet2
Status last verified
Jun 2019
First submitted
23 Apr 2018
Last updated
13 Sep 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ART-123 in people with Sepsis and Coagulopathy, run by Asahi Kasei Pharma America Corporation.

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 22 inclusion and 24 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: withdrawn, as of the sponsor's last update on 13 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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 (time frame: 28 days). 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 NCT03517501.

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 13 Sep 2019.

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