Mino-Lok Therapy (MLT) for the Treatment of CRBSI/CLABSI

NCT02901717 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: MDA-2013-0039
• Study Type: interventional
• Target: 144
• Locations: 2 countries
• Sites: 22

Brief Summary

This is a Phase 3, multi-center, randomized, open-label, assess-blind study to determine the efficacy and safety of MLT, a novel antibiotic lock therapy that combines minocycline with edetate disodium in 25% ethanol solution as an adjuctive therapy for the treatment of catheter-related or central line associated bloodstream infection (CRBSI/CLABSI). Approximately 144 subjects who have been diagnosed with CRBSI/CLABSI and who meet all necessary criteria for the study will be randomized in a 1:1 ratio to 1 of 2 treatment arms:

• MLT Arm: Mino-Lok therapy; or
• Control Arm: Antibiotic lock (±heparin). The antibiotic lock (ALT) should be comprised of the best available therapy at the sites based on standard institutional practices or recommendations from the Infectious Diseases Society of America (IDSA) guidelines.

Conditions

Catheter-related Infections

Outcome Measures

Primary Outcomes (1)

• Time to a catheter failure event.

  The time (in days following randomization) to a catheter failure event between randomization and TOC (Week 6) in the Intent-to-Treat (ITT) Population.

  6 weeks

Secondary Outcomes (6)

• Proportion of subjects with overall success in the MITT and CE populations.

  6 weeks

• Time to catheter failure in the MITT and CE Populations.

  6 weeks

• Microbiological eradication

  6 weeks

• Clinical Cure

  6 Weeks

• All-cause mortality

  6 weeks

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Antibiotic lock + standard of care antibiotics. The standard of care antibiotic will be chosen by the investigator at the time of the infection.

Drug: Antibiotic lock

Mino-Lok Therapy (MLT)

EXPERIMENTAL

Standard of care plus MLT. MLT contains minocycline with EDTA and ethanol.

Drug: Mino-Lok

Interventions

Mino-Lok DRUG

Standard of Care antibiotics appropriate for the infecting organism plus Mino-Lok therapy to disinfect and save the catheter.

Also known as: Standard of care antibiotics + Mino-Lok

Mino-Lok Therapy (MLT)

Antibiotic lock DRUG

Standard of Care antibiotics appropriate for the infecting organism with an antibiotic lock solution using the same standard of care antibiotic delivered systemically. The antibiotic lock arm may include subjects with S. aureus, including methicillin-resistant S. aureus, vancomycin intermediate S. aureus, or vancomycin-resistant S. aureus; vancomycin resistant enterococci; Candida, Pseudomonas; other Gram negative organisms; or other organisms deemed to be of high virulence per the Investigator. The standard of care antibiotic will be determined by the investigator at the start of treatment.

Also known as: Standard of Care antibiotics with antibiotic lock

Standard of Care

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject or a legally authorized representative must provide a signed informed consent form;
• Male or female at least 12 years of age;
• Subject must have a bloodstream infection with no other apparent source other than the CVC that meets one of the following criteria:
• A recognized single pathogen cultured from 1 or more blood cultures; OR
• A common skin contaminant cultured from 2 or more blood cultures drawn on the same or consecutive calendar days from a subject with fever (greater than or equal to 38.0 degrees C), chills, or hypotension (systolic blood pressure less than 90 mmHg); NOTE: When possible, it is recommended to collect from both the CVC and peripheral venipuncture.
• Inpatient or outpatient with presence of indwelling CVC (ie, totally implantable port, tunneled or non-tunneled CVC, hemodialysis catheter, or peripherally inserted CVC) that has been in place for at least 5 days;
• A bloodstream infection documented within 96 hours prior to enrollment (and from which an isolate of the baseline pathogen(s) is still available for analysis at the central laboratory) and demonstrates the protocol definition of CRBSI or CLABSI;
• NOTE: Subjects may be enrolled and randomized while awaiting results of standard blood cultures from the local laboratory:
• If an organism has been identified from blood specimen testing using an FDA-cleared rapid diagnostic test (eg, T2MR®); or
• If a positive blood culture specimen shows an organism by 1 of the following:
• Gram stain; or An FDA-cleared molecular rapid diagnostic test (eg, FilmArray® BCID or Verigene®); If the pending blood culture does not confirm a qualifying organism by standard methods and an isolate is not available for testing at the central laboratory, the subject will be withdrawn from study drug treatment and managed at the Investigator's discretion.
• NOTE: Subjects with a positive blood culture identified up to 120 hours prior to enrollment and in whom the baseline pathogen is still available for analysis at the central laboratory may be considered on a case by-case basis with prior approval from the Medical Monitor.
• Subjects for whom, in the Investigator's opinion, catheter retention for the duration of the study (6 weeks) is reasonable or required;
• Female subjects of childbearing potential must have a negative urine and/or serum pregnancy test within 5 days prior to randomization;
• NOTE: The following are considered women who are NOT of childbearing potential:

You may not qualify if:

• Subjects with hypersensitivity or allergy to tetracycline antibiotics or edetate disodium;
• Subjects with septic shock that requires inotropic support or is unresponsive to fluid resuscitation;
• Subjects taking disulfiram at the time of randomization or who are expected to take disulfiram at any time during treatment with study drug;
• Subjects with prosthetic cardiac valves, vascular grafts, pacers, automatic implantable cardioverter-defibrillator, or other non-removable vascular foreign body, with the exception of coronary stents and peripheral stents;
• Subjects with the presence of a deep-seated intravascular source of infection (eg, endocarditis \[as evidenced by vegetations on an echocardiogram or clinical suspicion\] or septic thrombosis);
• Subjects with bacteremia with documented microbiological evidence of another source of infection (eg, osteomyelitis, pneumonia, skin infection, urinary tract infection, joint infection, or abdominal infection) known to be due to the same organism cultured from the blood;
• Subjects with polymicrobial CRBSI/CLABSI caused by pathogens that would require multiple antibiotics to be used for adequate lock therapy treatment. For example, a subject with methicillin-resistant Staphylococcus aureus and Escherichia coli requiring treatment with vancomycin and meropenem would be excluded from the study. A subject with S. aureus and Staphylococcus epidermidis, where both are identified as pathogens and where both could be treated with vancomycin, would be eligible; NOTE: If more than 1 organism is isolated, the Investigator should decide which of the organisms are pathogens and require therapy. Isolates of all organisms should be sent to the central laboratory. In the event that the subject is being treated with more than 1 systemic standard of care (SOC) anti-infective, the Investigator will specify a single antibiotic that should be used for the antibiotic lock. It is acceptable for the SOC antibiotic lock to differ from the SOC anti infectives, as necessary per local SOC.
• Subjects with the presence of a tunnel or catheter exit site infection or an infusion port pocket abscess as manifested by purulence at the exit site, or inflammation with erythema, or induration of at least 1 cm in diameter;
• Subjects who have been previously randomized into the present study;
• Subjects who are pregnant or breastfeeding;
• Subjects with proven or suspected persistent bacteremia or fungemia despite 72 hours of both systemic anti-infective therapy and lock therapy to which the infecting organism is susceptible;
• Subjects with short-term CVCs indwelling at least 5 days;
• Subjects with a central line-related mycobacterial infection or fungi other than Candida; or
• Subjects who, in the opinion of the Investigator, have a high probability of death within 3 months of randomization due to a disease process other than the CRBSI/CLABSI.

Sponsors & Collaborators

• Leonard-Meron Biosciences, Inc.: lead

Study Sites (22)

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Florida Shands Hospital

Gainesville, Florida, 32608, United States

RECRUITING

Edward Hines Jr. VA Hospital

Hines, Illinois, 60141, United States

RECRUITING

AMG Oncology

Park Ridge, Illinois, 60068, United States

RECRUITING

Indiana Blood and Marrow Institute

Indianapolis, Indiana, 46237, United States

RECRUITING

Ascension Via Christi Hospital

Wichita, Kansas, 67214, United States

RECRUITING

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

SUSPENDED

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

SUSPENDED

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Henry Ford Health Systems

Detroit, Michigan, 48202, United States

RECRUITING

William Beaumont Hospital

Troy, Michigan, 48083, United States

SUSPENDED

VA Sierra Nevada Health Care Systems

Reno, Nevada, 89502, United States

RECRUITING

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

RECRUITING

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27858, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Salem VA Medical Center

Salem, Virginia, 24153, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

SUSPENDED

VA Caribbean Healthcare System

San Juan, PR, 00921, Puerto Rico

RECRUITING

Manati Medical Center

Manatí, Puerto Rico

RECRUITING

Ponce Research Institute

Ponce, Puerto Rico

RECRUITING

MeSH Terms

Conditions

Catheter-Related Infections

Condition Hierarchy (Ancestors)

Infections

Central Study Contacts

Alan Lader, Ph.D.

CONTACT

908-967-6677; clinops@citiuspharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 15, 2016
• Study Start: February 13, 2018
• Primary Completion: December 1, 2022
• Study Completion: March 1, 2023
• Last Updated: April 19, 2022

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (19); PR (3)