Septic ShockPhase 2SSAILNCT02317549

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

A Phase 2 study testing LB1148 in people with Septic Shock, run by Leading BioSciences, Inc at 34 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Septic Shock
What is being tested?: LB1148
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 34 sitesin 2 countries
Study dates: Apr 2015to Mar 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Show all 9Show fewer

Phenylephrine ≥25 µg/min;
Epinephrine ≥5 µg/min, or
Vasopressin ≥0.03 units/min.

Who cannot join

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.

Show all 46Show fewer

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:
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 or Cystic Fibrosis;
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 bone marrow, heart, lung, liver, pancreas, or small bowel transplantation), or
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 (past 28 days);
Active cerebrovascular bleed;
Active thromboembolic disease, (such as deep vein thrombosis, pulmonary embolism [PE], cerebral thrombosis, ischemic stroke, or acute coronary syndrome [ACS]);
Acute promyelocytic leukemia taking all-trans retinoic acid for remission induction or;
Continuing use of a combined hormonal contraceptive (including combined hormonal pill, patch or vaginal ring).
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.

Trial locations and contacts

34 sites in 2 countries.

Country

City, postcode or hospital

34 sites in 2 countries

United States26 sites

University of Michigan Health Center
Ann Arbor, Michigan, 48109
New York Methodist Hospital
Brooklyn, New York, 11215
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
Cooper University Hospital
Camden, New Jersey, 08103
UNC Chapel Hill
Chapel Hill, North Carolina, 27599
University of Virginia Health System
Charlottesville, Virginia, 22908
Henry Ford Hospital
Detroit, Michigan, 48202
Community Regional Medical Center, Fresno
Fresno, California, 93721
ARH Regional Medical Center
Hazard, Kentucky, 41701
Ben Taub Hospital
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
Long Beach Memorial Medical Center
Long Beach, California, 90806
University of Louisville Hospital Laboratory
Louisville, Kentucky, 40202
Froedtert Hospital and Medial College of Wisconsin
Milwaukee, Wisconsin, 53226
St. Patrick Hospital
Missoula, Montana, 59802
Providence Hospital
Mobile, Alabama, 36608
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
OU Medical Center
Oklahoma City, Oklahoma, 73104
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Mayo Clinic Labs - Rochester Campus
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
Baystate Medical Center
Springfield, Massachusetts, 01199
Barnes Jewish Hospital
St Louis, Missouri, 63110
Mercy St. Vincent Medical Center, Clinical Research Offices
Toledo, Ohio, 43608
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157

Other trials in United States

Canada8 sites

Peter Lougheed Centre
Calgary, Alberta, T1Y6J4
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Nova Scotia Health Authority
Halifax, Nova Scotia, B3H 3A7
St. Paul's Hospital
Vancouver, British Columbia, V6Z1Y6
Royal Jubilee Hospital
Victoria, British Columbia, V8R 1J8
Victoria General Hospital
Victoria, British Columbia, V8Z 6R5
St Boniface Hospital
Winnipeg, Manitoba, R2H 2A6
WHRA Winnipeg Health Sciences
Winnipeg, Manitoba, R3A 1R9

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

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:

Reduce mortality at Day 7, Day 28 and Day 90;
Reduce the number of days to organ dysfunction resolution as evidenced by Sequential Organ Failure Assessment (SOFA) score ≤2 in patients alive on Day 28;
Reduce the daily organ dysfunction as evidenced by average SOFA score through Day 14 and Day 28;
Reduce the number of patients with new-onset organ dysfunction at Day 8;
Increase the number of days alive and free from renal replacement therapy through Day 28;
Increase the number of days alive and free from renal dysfunction through Day 28;
Increase the number of days alive and ventilator free through Day 28;
Increase the number of days alive and free of vasopressors through Day 14 and Day 28;
Increase the numbers of days alive and free from liver dysfunction through Day 28;
Increase the number of days alive and not in the Intensive Care Unit (ICU) through Day 28;
Increase the number of days alive and not in the hospital through Day 28, and
Improve patient functional outcomes through Day 28 as evidenced by the EuroQoL EQ 5D questionnaire.

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:

Reduce the number of patients with new-onset organ dysfunction from Day 9 through Day 16;
Decrease the number of days to normalize serum lactate (≤2.2 mmol/L) through Day 28;
Reduce the average daily serum lactate levels through Day 8;
Increase the number of days alive and free from ileus through Day 8 and Day 28.

Conditions: Septic Shock
Being tested: LB1148, Placebo
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
Medical subject headings: Shock, Septic, Sepsis, Shock, Systemic Inflammatory Response Syndrome, Infections, Toxemia, Multiple Organ Failure, Hyperlactatemia

What participants receive

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

LB1148Drug
Also called Tranexamic Acid
PlaceboDrug

Study groups in NCT02317549
Study group	Role	What they receive
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 Receives: 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 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Through day 28.

Timeline

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

Apr 2015Mar 2016

First posted16 Dec 2014 (estimated)
Study startApr 2015
Primary completionMar 2016
Study completionMar 2016

Why it stopped: Inability to enroll

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Septic ShockStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02317549
Sponsor's protocol ID: LBS-SS201
Acronym: SSAIL
Status last verified: May 2020
First submitted: 11 Dec 2014
Last updated: 1 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis

All Septic Shock trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Septic Shock by Inhibiting Autodigestion and Preserving Gut Integrity With Enteric LB1148 (SSAIL Trial)
ClinicalTrials.gov ID: NCT02317549
Acronym / sponsor ID: SSAIL / LBS-SS201
Conditions: Septic Shock
Keywords: sepsis, septic shock, vasodilatory shock, circulatory shock, Systemic Inflammatory Response Syndrome, SIRS, infection, toxemia
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Inability to enroll
Enrolment: 8 participants (actual)
Lead sponsor: Leading BioSciences, IncIndustry (pharma, biotech, devices)
Study start: Apr 2015
Primary completion: Mar 2016 (actual)
Study completion: Mar 2016 (actual)
First posted: 16 Dec 2014 (estimated)
Results: Posted 20 Nov 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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:

Reduce mortality at Day 7, Day 28 and Day 90;
Reduce the number of days to organ dysfunction resolution as evidenced by Sequential Organ Failure Assessment (SOFA) score ≤2 in patients alive on Day 28;
Reduce the daily organ dysfunction as evidenced by average SOFA score through Day 14 and Day 28;
Reduce the number of patients with new-onset organ dysfunction at Day 8;
Increase the number of days alive and free from renal replacement therapy through Day 28;
Increase the number of days alive and free from renal dysfunction through Day 28;
Increase the number of days alive and ventilator free through Day 28;
Increase the number of days alive and free of vasopressors through Day 14 and Day 28;
Increase the numbers of days alive and free from liver dysfunction through Day 28;
Increase the number of days alive and not in the Intensive Care Unit (ICU) through Day 28;
Increase the number of days alive and not in the hospital through Day 28, and
Improve patient functional outcomes through Day 28 as evidenced by the EuroQoL EQ 5D questionnaire.

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:

Reduce the number of patients with new-onset organ dysfunction from Day 9 through Day 16;
Decrease the number of days to normalize serum lactate (≤2.2 mmol/L) through Day 28;
Reduce the average daily serum lactate levels through Day 8;
Increase the number of days alive and free from ileus through Day 8 and Day 28.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Tranexemic Acid	Experimental	Drug: LB1148Daily 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
Placebo	Placebo comparator	Drug: PlaceboDaily a total of 700 mL of Placebo solution will be administered orally or via NG/OG/NJ/ND/PEG tube

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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:

Key exclusion criteria (46 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LB1148Also: Tranexamic Acid	Drug	Tranexemic Acid
Placebo	Drug	Placebo

Primary outcome

Number of Days Alive Without Cardiovascular, Renal or Pulmonary Organ Support
Time frame: Through day 28.
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.

Results and safety

Results posted to the registry on 20 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tranexemic Acid	5	5
Placebo	3	3

Primary outcome: Number of Days Alive Without Cardiovascular, Renal or Pulmonary Organ Support

Time frame: Through day 28.. Mean (Full Range). Unit: days

Measure	Tranexemic Acid n = 5	Placebo n = 3
Value	14 (0 to 23)	26 (26 to 27)

Population analysed: 5 subjects were treated with LB1148, and 3 subjects were treated with placebo. Upon review of patient charts after the study was terminated, 1 patient on placebo was enrolled on the basis of a Glasgow Coma Score calculated while under sedation, which allowed SOFA score to meet study criteria and the patient to be inappropriately enrolled.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tranexemic Acid	3 of 5 (60%)	3 of 5 (60%)	Not reported
Placebo	1 of 3 (33.3%)	3 of 3 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Septic Shock

Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Tom Hallam, PhD study chair

Vice President

34 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LB1148 in people with Septic Shock, run by Leading BioSciences, Inc at 34 sites in 2 countries.

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 9 inclusion and 46 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: stopped early, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Days Alive Without Cardiovascular, Renal or Pulmonary Organ Support (time frame: Through day 28.). 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 NCT02317549.

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 1 Jun 2020.