Treatment of Septic Shock by Inhibiting Autodigestion and Preserving Gut Integrity With Enteric LB1148

NCT02317549 | Terminated Phase 2 Results DMC

• 1 other identifier: LBS-SS201
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 34

Brief Summary

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.

Conditions

Septic Shock

Keywords

sepsis; septic shock; vasodilatory shock; circulatory shock; Systemic Inflammatory Response Syndrome; SIRS; infection; toxemia; gut barrier breakdown; autodigestion; multiorgan failure; MOF; multiorgain dysfunction syndrome; MODS; hyperlactatemia; tissue hypoxia

Outcome Measures

Primary Outcomes (1)

• Number of Days Alive Without Cardiovascular, Renal or Pulmonary Organ Support

  The patient will be classified as having organ support if organ support is required through the use of: * Mechanical ventilation; * Vasopressors to maintain adequate blood pressure (BP), or * Renal replacement therapy.

  Through day 28.

Study Arms (2)

Tranexemic Acid

EXPERIMENTAL

Daily a total of 700 mL of LB1148 solution containing 7.5 g of tranexemic acid will be administered orally or via NG/OG/NJ/ND/PEG tube

Drug: LB1148

Placebo

PLACEBO COMPARATOR

Daily a total of 700 mL of Placebo solution will be administered orally or via NG/OG/NJ/ND/PEG tube

Drug: Placebo

Interventions

LB1148 DRUG

Also known as: Tranexamic Acid

Tranexemic Acid

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Norepinephrine ≥5 µg/min;
• Dopamine ≥10 µg/kg/min;
• Phenylephrine ≥25 µg/min;
• Epinephrine ≥5 µg/min, or
• Vasopressin ≥0.03 units/min.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leading BioSciences, Inc: lead

Study Sites (34)

Providence Hospital

Mobile, Alabama, 36608, United States

Location

Community Regional Medical Center, Fresno

Fresno, California, 93721, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

ARH Regional Medical Center

Hazard, Kentucky, 41701, United States

Location

University of Louisville Hospital Laboratory

Louisville, Kentucky, 40202, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

University of Michigan Health Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic Labs - Rochester Campus

Rochester, Minnesota, 55905, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

St. Patrick Hospital

Missoula, Montana, 59802, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Mercy St. Vincent Medical Center, Clinical Research Offices

Toledo, Ohio, 43608, United States

Location

OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Ben Taub Hospital

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Froedtert Hospital and Medial College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y6J4, Canada

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

Location

Victoria General Hospital

Victoria, British Columbia, V8Z 6R5, Canada

Location

St Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

WHRA Winnipeg Health Sciences

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 3A7, Canada

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Shock; Systemic Inflammatory Response Syndrome; Infections; Toxemia; Multiple Organ Failure; Hyperlactatemia

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

Due to the Sponsor decision to terminate the study, data was not monitored or cleaned. The study data that are available for the 8 enrolled patients has been evaluated. However, there are too few patients to draw any meaningful conclusions.

Results Point of Contact

• Title: Tom Hallam, PhD, MBA
• Organization: Leading BioSciences

tom.hallam@leadingbiosciences.com

631-739-3088

Study Officials

• Tom Hallam, PhD

  Vice President

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2014
• First Posted: December 16, 2014
• Study Start: April 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: June 1, 2020
• Results First Posted: November 20, 2017

Record last verified: 2020-05

Locations

US (26); CA (8)