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Trial record 9 of 17 for:    Necrotizing Fascitis

Phase III Efficacy and Safety Study of AB103 in the Treatment of Patients With Necrotizing Soft Tissue Infections (ACCUTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02469857
Recruitment Status : Active, not recruiting
First Posted : June 12, 2015
Last Update Posted : August 6, 2019
Biomedical Advanced Research and Development Authority
Information provided by (Responsible Party):
Atox Bio Ltd

Brief Summary:
The purpose of this study is to determine whether AB103 is safe and effective in the treatment of patients with necrotizing soft tissue infections receiving standard of care therapy.

Condition or disease Intervention/treatment Phase
Necrotizing Soft Tissue Infections Necrotizing Fasciitis Fournier's Gangrene Drug: AB103 0.5 mg/kg Other: NaCl 0.9% Phase 3

Detailed Description:

The primary hypothesis of this study is that in addition to standard of care treatment (which includes surgical intervention, antimicrobial therapy and critical care support for organ dysfunction or failure), AB103 will demonstrate a clinically significant treatment benefit over placebo.

This hypothesis will be addressed by measuring the effect of AB103 on a composite of clinical parameters associated with the disease course of patients with NSTI, using a responder analysis. A responding patient must meet all 5 parameters of the composite clinical success end point, while a non-responding patient can fail by not meeting any one of the parameters. These analyses are designed to demonstrate that in addition to being safe, one dose of 0.5 mg/kg of AB103 will:

Improve systemic signs of the infection by improving organ function of patients compared to placebo as measured by:

  • Survival at Day 28
  • Modified SOFA (mSOFA) score on Day 14 and change from baseline to Day 14 ≥ 3. A Day 14 mSOFA score of ≤1 and a change from baseline (pre-treatment) to Day 14 ≥3 will be required for a patient to achieve the primary composite clinical success endpoint (NICCE)

Improve the local signs of the infection, as measured by:

  • Reduced number of debridements, counted to Day 14. No more than 3 debridements to Day 14 will be required for a patient to achieve composite clinical success
  • No amputation after the first debridement (amputation on the first debridement is not considered a failure). A patient will be required to have had no amputations done after the first surgical procedure in order to achieve composite clinical success.

    290 patients will be recruited into the study and randomized to receive either 0.5 mg/kg AB103 or placebo in a 1:1 ratio. Randomization will be stratified within center by the diagnosis of Fournier's Gangrene and mSOFA score category (3-4 vs >4) at screening. The study will be conducted with interim analyses for futility at 100 patients and safety monitored by an independent Data Monitoring Board at regular planned intervals.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study of AB103 as Compared to Placebo in Patients With Necrotizing Soft Tissue Infections. ACCUTE (AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections)
Actual Study Start Date : December 2015
Actual Primary Completion Date : July 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: AB103 0.5 mg/kg
AB103 0.5 mg/kg, IV, single dose
Drug: AB103 0.5 mg/kg
Other Name: p2TA

Placebo Comparator: NaCl 0.9%
NaCl 0.9%, IV, single dose
Other: NaCl 0.9%
Other Name: Normal saline

Primary Outcome Measures :
  1. NICCE: Clinical composite success end point [ Time Frame: 28 days ]
    Success is defined as meeting all 5 components of the composite score: Alive until Day 28, (ii) Day 14 debridements ≤3 (iii) No amputation done after the first debridement (iv) Day 14 mSOFA score ≤1 (v) Reduction of ≥3 score points between Baseline and Day 14 mSOFA score

  2. Modified clinical composite endpoint: [ Time Frame: 28 days ]
    Success is defined as meeting all 3 components of the composite score: Alive until Day 28, (ii) Day 14 debridements ≤3 (iii) No amputation done after the first debridement

Secondary Outcome Measures :
  1. Safety measures Adverse Events [ Time Frame: 28 days ]
    Measures throughout Day 28: Adverse Events (includes Serious Adverse Events (SAEs).

  2. Safety measures Clinical safety laboratory [ Time Frame: 28 days ]
    Measures throughout Day 14: Clinical safety laboratory

  3. Safety measures Secondary infections [ Time Frame: 28 days ]
    Measures throughout Day 28: Secondary infections

  4. Recovery from acute kidney injury [ Time Frame: 28 days ]
  5. Time to resolution of mSOFA score to ≤ 1 [ Time Frame: 14 days ]
  6. Critical care and hospital stay parameters ICU days [ Time Frame: 28 days ]
    ICU days

  7. Critical care and hospital stay parameters Ventilator days [ Time Frame: 28 days ]
    Ventilator days

  8. Critical care and hospital stay parameters Hospital length of stay [ Time Frame: 28 days ]
    Hospital length of stay

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Surgical confirmation of NSTI by attending surgeon;
  2. mSOFA score ≥3 (in any one or combination of the 5 major components of SOFA score with one organ component having a score of at least 2: cardiovascular, respiratory, renal, coagulation, CNS), measured as close as possible to the first debridement;
  3. IV drug administration within 6 hours from the clinical diagnosis and the decision at the study site, to have an urgent surgical exploration and debridement (drug should not be administered until surgical confirmation is established);
  4. If a woman is of childbearing potential, she must consistently use an acceptable method of contraception from baseline through Day 28;
  5. If a male patient's sexual partner is of childbearing potential, the male patient must acknowledge that they will consistently use an acceptable method of contraception (defined above) from baseline through Day 28.
  6. Signed and dated ICF as defined by the IRB and, if applicable, California Bill of Rights. If patient is unable to comprehend or sign the ICF, patient's legally acceptable representative may sign the ICF

Exclusion Criteria:

  1. BMI>51;
  2. Patient who has been operated at least once for the current NSTI infection and had a curative deep tissue debridement;
  3. Patients with overt peripheral vascular disease in the involved area ;
  4. Diabetic patients with peripheral vascular disease who present with below the ankle infection;
  5. Removed DVT in area of NSTI as an exclusion criteria
  6. Patient with burn wounds;
  7. Current condition of: (a) Inability to maintain a mean arterial pressure > 50 mmHg and/or systolic blood pressure > 70 mmHg for at least 1 hour prior to screening despite the presence of vasopressors and IV fluids or (b) a patient with respiratory failure such that an SaO2 of 80% cannot be achieved or (c) a patient with refractory coagulopathy (INR >5) or thrombocytopenia (platelet count <20,000) that does not partially correct with administration of appropriate factors or blood products;
  8. Chronic neurological impairment that leads to a neuro mSOFA component ≥2;
  9. Recent cerebrovascular accident in the last 3 months;
  10. Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past 30 days;
  11. Patient is not expected to survive throughout 28 days of study due to underlying medical condition, such as poorly controlled neoplasm;
  12. Patient or patient's family are not committed to aggressive management of the patient's condition;
  13. Any concurrent medical condition, which in the opinion of the Investigator, may compromise the safety of the patient or the objectives of the study or the patient will not benefit from treatment such as:

    • CHF {NYHA class III-IV}
    • Severe COPD
    • Liver dysfunction {Childs-Pugh class C}
    • Immunosuppression (see Appendix F, Section 15.6 for list of excluded immunosuppressive medications)
    • Neutropenia < 1,000 cells/mm3not due to the underlying infection
    • Idiopathic Thrombocytopenia Purpura
    • Receiving or about to receive chemotherapy or biologic anti-cancer treatment although hormonal manipulation therapies for breast and prostate malignancies are permitted
    • Hematological and lymphatic malignancies in the last 5 years;
  14. Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes;
  15. Patients with known chronic kidney disease (documented pre-illness creatinine value(s) ≥2.0) or patients receiving renal replacement therapy for chronic kidney disease;
  16. Patients that are treated with continuous hemofiltration (e.g. Continuous Veno-Venous Hemofiltration) for acute kidney dysfunction, not due to NSTI, starting prior to study drug administration;
  17. Pregnant or lactating women;
  18. Previous enrollment in a clinical trial involving investigational drug or a medical device within 30 days;
  19. Previous enrollment in this protocol, ATB-202 or the Phase 2 trial of AB103, ATB-201.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02469857

  Hide Study Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Maricopa Medical Center
Phoenix, Arizona, United States, 85008
Banner University Medical Center
Tucson, Arizona, United States, 24857
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center
Los Angeles, California, United States, 90502
University of California, Davis Medical Center
Sacramento, California, United States, 95817
UCSD Medical Center
San Diego, California, United States, 92103
United States, Colorado
UCH-Memorial Health System
Colorado Springs, Colorado, United States, 80909
University of Colorado Hospital
Denver, Colorado, United States, 80045
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
UF Health Shands Hospital
Gainesville, Florida, United States, 32610
Ryder Trauma Center/Jackson Memorial Hospital
Miami, Florida, United States, 33136
United States, Georgia
Emory University at Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Augusta University Health
Augusta, Georgia, United States, 30912
United States, Iowa
University of Iowa Hospital and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Louisiana
Our Lady of the Lake Regional Medical Center
Baton Rouge, Louisiana, United States, 70808
Baton Rouge General Hospital
Baton Rouge, Louisiana, United States, 70809
LSU Health Science Center
New Orleans, Louisiana, United States, 70112
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
United States, Maryland
University of Maryland R Adams Cowley Shock Trauma Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Wayne State University-Detroit Receiving Hospital
Detroit, Michigan, United States, 48201
Henry Ford Health System
Detroit, Michigan, United States, 48202
Wayne State University-Sinai Grace Hospital
Detroit, Michigan, United States, 48235
United States, Minnesota
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65211
St Louis University
Saint Louis, Missouri, United States, 63103
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
Capital Health System, Inc.
Trenton, New Jersey, United States, 98638
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Erie County Medical Center-Affliate of SUNYat Buffalo
Buffalo, New York, United States, 14215
Staten Island University Hospital-Northwell Health
Staten Island, New York, United States, 10305
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28208
East Carolina University
Greenville, North Carolina, United States, 27834
United States, Ohio
University of Cincinnati Medical Center (UCMC)
Cincinnati, Ohio, United States, 45219
The MetroHealth System
Cleveland, Ohio, United States, 44109
The Ohio State University
Columbus, Ohio, United States, 43210
Wright State University & Premier Health Clinical Trials Research Alliance
Dayton, Ohio, United States, 45409
St Elizabeth Youngstown Hospital
Youngstown, Ohio, United States, 44501
United States, Oregon
Legacy Emanuel Hospital
Portland, Oregon, United States, 97227
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's University Health Network
Bethlehem, Pennsylvania, United States, 18015
The Pennsylvania State University and The Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
The Trauma Center at PENN
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Tech University Health Sciences Center at El Paso
El Paso, Texas, United States, 79905
John Peter Smith Health Network
Fort Worth, Texas, United States, 76104
Baylor College of Medicine-Ben Taub Hospital
Houston, Texas, United States, 77030
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Scott and White Medical Center
Temple, Texas, United States, 76502
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98104
United States, Wisconsin
Medical College of Wisconsin-Froedtert Hospital
Milwaukee, Wisconsin, United States, 53226
Hộpital Estaing-CHU de Clermont-Ferrand
Clermont-Ferrand, France
Hộpital Henri Mondor
Créteil, France
Hôpital Bicêtre
Le Kremlin-Bicêtre, France
Robert Salengro Hopital-CHRU Lille
Lille, France
CHU de Limoges
Limoges, France
Hôpital Edouard Herriot
Lyon, France
CHRU Nancy, Hôpital Central
Nancy, France
CHU de Nimes
Nîmes, France
Hôpital de la Source, CHR Orleans
Orléans, France
CHRU Bretonneau
Tours, France
Sponsors and Collaborators
Atox Bio Ltd
Biomedical Advanced Research and Development Authority
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Study Director: Wayne M Dankner, MD Atox Bio Ltd
Principal Investigator: Eileen M Bulger, MD Harborview Injury Prevention and Research Center

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Responsible Party: Atox Bio Ltd Identifier: NCT02469857     History of Changes
Other Study ID Numbers: ATB-202
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Atox Bio Ltd:
Necrotizing fasciitis
Additional relevant MeSH terms:
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Fasciitis, Necrotizing
Communicable Diseases
Soft Tissue Infections
Fournier Gangrene
Musculoskeletal Diseases
Pathologic Processes
Skin Diseases, Bacterial
Bacterial Infections
Genital Diseases, Male