A Study of the Treatment of Septic Shock by Inhibiting Autodigestion and Preserving Gut Integrity with Enteric LB1148

Overview

About this study

Septic shock is a potentially life-threatening condition that can result in multi-organ dysfunction syndrome (MODS) and mortality. LB1148 was formulated to preserve gut integrity during physiological shock and help decrease the subsequent autodigestion leading to MODS and mortality. The purpose of this study in septic shock patients is to determine if enteral administration of LB1148 will increase the number of days alive without cardiovascular, pulmonary or renal replacement therapy through Day 28.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • First episode (during the current hospitalization) of documented or suspected sepsis of peritoneum/abdomen, soft tissue, blood, or non-hospital acquired lung origin
  • Must be receiving antimicrobial therapy for documented or suspected infection
  • Must have septic shock requiring vasopressors despite adequate fluid resuscitation of 30 mL/kg crystalloid or colloid equivalent, for either an SBP ≤ 90 mmHg or a MAP ≤ 65 mmHg
    • 30 mL/kg crystalloid is equivalent to 15 mL/kg colloids
  • Must have a continuous requirement for vasopressor support for at least 4 hours and, at randomization, on a minimum dose of at least 1 of the following vasopressors
    • Norepinephrine ≥5 µg/min
    • Dopamine ≥10 µg/kg/min
    • Phenylephrine ≥25 µg/min
    • Epinephrine ≥5 µg/min
    • Vasopressin ≥0.03 units/min
  • Must have a serum lactate level ≥ 4.0 mmol/L
  • Must be willing and able to comply with all required study procedures per protocol 
  • Must have a subsequent serum lactate measurement ≥ 3.0 mmol/L after adequate fluid resuscitation and at least 4 hours after the qualifying lactate was drawn. The first serum lactate and subsequent serum lactate measurements must be separated by at least 4 hours and the subsequent serum lactate must not have improved > 50% from the first

 

Exclusion Criteria

  • Not eligible for participation in the study if meeting ANY of the following criteria
    • Age < 18 or age ≥ 76 years
    • Time elapsed since onset of shock is > 24 hours
      • Onset of shock is defined as the first administration of a vasopressor given by continuous infusion (i.e. not a single bolus of norepinephrine, phenylephrine, or ephedrine)
    • Septic shock episode is the second or greater episode in current hospitalization 
      • Patients transferred from another healthcare facility that are still within the first 24 hours of the first episode of shock are eligible
    • Have hospital acquired pneumonia
    • Have genitourinary infections as the cause of septic shock
    • Unable to maintain a minimum MAP of 65 mmHg despite the presence of vasopressors and IV fluids
      • Brief transient BPs below 65 mmHg are not disqualifying
    • Have a serum lactate level  > 12.0 mmol/L at any point during the screening period
    • Serum lactate levels have improved (decreased) by greater than 50% at all subsequent assessments
      • If a patient has more than 2 serum lactate measurements, an interim measurement > 50% clearance does not exclude the patient if the patient still has 2 measurements that are separated by 4 hours and the subsequent of which has not improved by greater than 50% (and is ≥3.0 mmol/L)
    • Highest total SOFA score (known to staff at the time of randomization) during the screening period < 9
      • Each individual organ component sub-score is calculated from the highest (worst) score obtained for that organ during the screening period, up until randomization
    • Highest total SOFA score (known to staff at the time of randomization) during the screening period >18
      • Each individual organ component sub-score is calculated from the highest (worst) score obtained for that organ during the screening period
    • Lack of commitment to aggressive source control of infection
    • The patient or patient's surrogate fails to voluntarily sign an informed consent form (ICF)
    • Ineligible for feeding tube placement
    • Chronic renal insufficiency requiring hemodialysis not associated with the current episode of sepsis
    • Chronic pulmonary dysfunction requiring mechanical ventilation unrelated to the current episode of sepsis
    • Undergoing active radiation or cytotoxic chemotherapy treatment for uncontrolled malignancy
      • Hormonal and surgical therapies are permitted
    • Presence of third degree burns involving > 20% body surface area in the 7 days prior to study entry
    • Known inability to take the study medication (i.e. complete small bowel obstruction)
    • Has acute meningitis
    • Not expected to survive for at least 28 days due to a preexisting, non shock related medical condition. These include but are not limited to
      • HIV-positive patients whose most recent CD4 count was ≤50/mm3
      • Neutrophils <1000/mm3 unless due to sepsis
      • Received chest compressions as part of CPR during this hospitalization without neurologic recovery
      • Poorly controlled neoplasm
      • End-stage lung disease
      • End-stage liver disease (Child-Pugh Class C score >10, evidence of portal hypertension or esophageal varices)
      • Severe congestive heart failure (New York Heart Association [NYHA] Class IV or pre-sepsis ejection fraction <30%)
      • Undergone organ transplant including, but not limited to
        • Bone marrow
        • Heart
        • Lung
        • Liver
        • Pancreas
        • Kidney
        • Small bowel
      • Primary ICU admitting diagnosis of acute myocardial infarction (MI)
    • Have relative contraindications to taking TXA or have a believed adverse risk/benefit ratio for taking the drug. These include patients with 
      • Known sensitivity to TXA
      • Recent craniotomy
      • Active cerebrovascular bleed
      • Active thromboembolic disease, such as
        • Deep vein thrombosis
        • Pulmonary embolism [PE]
        • Cerebral thrombosis
        • Ischemic stroke
        • Acute coronary syndrome [ACS]
      • Acute promyelocytic leukemia taking all-trans retinoic acid for remission induction
    • Exclusion for any other condition that, in the opinion of the investigator or coordinating center, would preclude the subject from being an appropriate candidate for the study
    • Received any other investigational therapy or device within 4 weeks prior to screening
    • Female patients of childbearing potential with
      • a positive urine or serum pregnancy test 
      • not taking or not willing to take acceptable birth control measures through Day 28 
        • Abstinence
        • Intrauterine devices 
        • Barrier methods
    • Those women who are lactating and insist on breast feeding within 5 days of the last dose of study drug if their sepsis resolves
      • Post-partum patients who have a persistent positive pregnancy test (human chorionic gonadotropin [HCG] values which have not had time to decrease) will be allowed in the study.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

John Park, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20205989

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