Treatment of Septic Shock by Inhibiting Autodigestion and Preserving Gut Integrity With Enteric LB1148 (SSAIL Trial)
Treatment of Septic Shock by Inhibiting Autodigestion and Preserving Gut Integrity With Enteric LB1148 (SSAIL Trial)
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 ameliorate 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.
Primary Objective(s):
The primary objective of this study is to determine if enteral administration of LB1148 will increase the number of days alive without cardiovascular, renal or pulmonary organ support through Day 28.
The secondary objectives of this study are to determine if LB1148 will:
In addition, the study will assess the safety and tolerability of LB1148 in patients with septic shock.
The exploratory objectives of this study are to determine if LB1148 will:
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 (i.e. must have been unable to maintain adequate blood pressure despite adequate fluid resuscitation without the use of vasopressors). Note: 30 mL/kg crystalloid is equivalent to 15 mL/kg colloids.
Must have a requirement for vasopressor support after adequate fluid resuscitation, and, at randomization, must require a minimum dose of at least 1 of the following vasopressors:
Exclusion Criteria
Patients will not be eligible for participation in the study if they meet 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.
Note: 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 60 mmHg despite the presence of vasopressors and IV fluids.
Note: brief transient BPs below 60 mmHg are not disqualifying.
Have a serum lactate measurement <2.5 mmol/L after adequate fluid resuscitation (refer to Inclusion Criteria #3).
Not expected to survive for at least 28 days due to a preexisting, non-shock related medical condition.
Highest total SOFA score (known to staff at the time of randomization) during the screening period <6.
Note: 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.
Note: 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.
Note: 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.
Have any of the following medical conditions:
Have relative contraindications to taking TXA or have a believed adverse risk/benefit ratio for taking the drug. These include patients with:
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 or who are not taking (or not willing to take) acceptable birth control measures (abstinence, intrauterine devices, contraceptive implants or barrier methods) through Day 28. Additionally, those women who are lactating and insist on breast feeding within 5 days of the last dose of study drug if their sepsis resolves.
Note: 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.