Clinical Trials

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.