Phase 3 Study of Reltecimod vs Placebo in Patients With Sepsis-associated Acute Kidney Injury
- Conditions
- Necrotizing Soft Tissue InfectionPeritonitisAcute Kidney Injury
- Interventions
- Drug: Placebo
- Registration Number
- NCT03403751
- Lead Sponsor
- Atox Bio Ltd
- Brief Summary
Phase 3 multicenter study to be conducted in up to 90 qualified participating sites globally to assess the efficacy and safety of Reltecimod vs placebo in patients with sepsis-associated Stage 2/3 AKI.
- Detailed Description
Phase 3 randomized, placebo controlled study assessing the efficacy (complete recovery from AKI) and safety of Reltecimod in patients with suspected or confirmed abdominal sepsis (planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures for control of underlying abdominal infection within 24 hours of evaluation by medical personnel) or patients with surgically confirmed necrotizing soft tissue infection (NSTI), requiring intensive care unit (ICU) or step down unit admission and in whom the diagnosis of Stage 2/3 acute kidney injury (AKI; as defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria) is established at initial presentation for medical evaluation or up to 48 hours from the suspected diagnosis of abdominal sepsis or from surgically confirmed diagnosis of NSTI.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 58
-
Has either suspected or documented diagnosis of abdominal sepsis requiring treatment with parenteral antibiotics and planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures within 24 hours of evaluation by medical personnel. Recommended surgical or interventional radiologic procedures be performed with 12 hours of evaluation by medical personnel.
-
Initial diagnosis of AKI Stage 2 or 3 according to KDIGO AKI criteria established either upon presentation to medical care in those patients with suspected abdominal sepsis or in those patients in whom the initial diagnosis of AKI is established during the 48 hour period from the suspected diagnosis of abdominal sepsis.
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Study medication must be administered within 6 hours of confirmation of onset of Stage 2 or 3 AKI as established at the study site, under the following criteria:
- After the decision is made by the attending surgeon at the study site for a surgical or interventional radiology procedure for the abdominal infection OR
- After confirmed diagnosis of abdominal infection has been established by a surgical or interventional radiology procedure
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Has known prior history of chronic kidney disease (CKD( with a documented estimated GFR (eGFR) < 30 mL/min
• Exception: Patients with history of CKD but no available prior eGFR who have documented normal kidney size on ultrasound or computed tomography evaluation (performed within 90 days of screening) will be eligible
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Patients receiving renal replacment therapy (RRT) for CKD
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. Previously diagnosed with documented AKI in the last 30 days
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Documented primary glomerular disease or toxic tubulo-interstitial nephritis at the time of AKI diagnosis
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Patient is not expected to survive throughout 28 days of study due to significant underlying medical condition
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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:
- Congestive heart failure (CHF) {New York Heart Association (NYHA) class III-IV}
- Severe chronic obstructive pulmonary disease (COPD) {GOLD - Global Initiative for Chronic Obstructive Lung Disease - stage IV. or chronic hypoxemia)
- Liver dysfunction {Childs-Pugh class C}
- Primary or acquired immunodeficiency or immunosuppression due to treatment with immunosuppressive medications
- Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes
- Neutropenia < 1,000 cells/mm3 not due to the underlying infection
- Receiving or about to receive chemotherapy or biologic anti-cancer treatment,
- Hematological and lymphatic malignancies in the last 5 years
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Patient has acute pancreatitis with no established source of infection, uncomplicated appendicitis, or cholangitis or cholecystitis without peritonitis;
-
Pregnant or lactating women
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Concurrent or previous enrollment in a clinical trial involving investigational drug or a medical device
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reltecimod 0.5 mg/kg Reltecimod 0.5 mg/kg Single IV infusion of Reltecimod 0.5 mg/kg Placebo Placebo Single IV infusion of 0.9% Sodium Chloride Injection (Normal Saline)
- Primary Outcome Measures
Name Time Method Freedom From Durable Loss of Renal Function at Day 28 28 Days Freedom from durable loss of renal function at Day 28 required all of the following 3 components: alive at Day 28, free of dialysis at Day 28, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 28 from patient reference eGFR (measured by Modification of Diet in Renal Disease \[MDRD\] formula).
Serious Adverse Events (SAEs) 28 Days Number of patients experiencing at least one SAE
Adverse Events (AEs) 28 Days The number of patients experiencing at least one AE.
- Secondary Outcome Measures
Name Time Method ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category 28 Days The number of days a patient did not spend in the ICU through Day 28, by mSOFA category (mSOFA total score of 1 or less; mSOFA total score of 2 or more). Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.
Intensive Care Unit (ICU)-Free Days 28 Days ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.
Ventilator-free Days 28 Days Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.
Hospital Days 90 Days Hospital days refers to the number of days a patient spent time in the hospital.
Cumulative Number of Deaths 90 Days The number of deaths occurring through Day 90
Secondary Infections 28 Days Number of patients experiencing at least one secondary infection
Freedom From Durable Loss of Renal Function at Day 14 14 Days Freedom from durable loss of renal function at Day 14 required all of the following 3 components: alive at Day 14, free of dialysis at Day 14, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 14 from patient reference eGFR (measured by Modification of Diet in Renal Disease \[MDRD\] formula).
Vasopressor-free Days 28 Days Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.
Ventilator-free Days by Day 14 mSOFA Category 28 Days The number of days a patient was not on a ventilator through Day 28, by mSOFA category
Vasopressor-free Days by Day 14 mSOFA Category 28 Days The number of days a patient was not receiving a vasopressor through Day 28, by mSOFA category
Hospital Days by Day 14 mSOFA Category 90 Days The number of days a patient was in the hospital.
Hospital Discharge Location by Day 14 mSOFA Category 90 Days Number of patients with more favorable discharge location (home or rehabilitation facility) or less favorable discharge location (skilled nursing facility, another acute care facility, death, other) among patients alive at Day 14.
Trial Locations
- Locations (56)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
UCSD Medical Center
🇺🇸San Diego, California, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
St. Luke's University Health Network
🇺🇸Bethlehem, Pennsylvania, United States
The Pennsylvania State University and The Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
CHRU la Cavale Blanche
🇫🇷Brest, France
Hopital Saint Eloi
🇫🇷Montpellier, France
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Hopital Edouard Herriot
🇫🇷Lyon, France
Hopital Victor Dupouy
🇫🇷Argenteuil, France
CH Le Mans
🇫🇷Le Mans, France
Robert Salengro Hopital-CHRU Lille
🇫🇷Lille, France
Banner University Medical Center
🇺🇸Tucson, Arizona, United States
CHU de Nante Hotel-Dieu
🇫🇷Nantes, France
Nouvel Hopital Civil
🇫🇷Strasbourg, France
Hopital Cochin
🇫🇷Paris, France
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
CHU Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHU de Limoges
🇫🇷Limoges, France
LSU Health Science Center
🇺🇸New Orleans, Louisiana, United States
CHU Lyon Sud
🇫🇷Lyon, France
CHU Nimes
🇫🇷Nîmes, France
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
CHU Rennes
🇫🇷Rennes, France
UCH-Memorial Health System
🇺🇸Colorado Springs, Colorado, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
The Trauma Center at PENN
🇺🇸Philadelphia, Pennsylvania, United States
Erie County Medical Center-Affliate of SUNYat Buffalo
🇺🇸Buffalo, New York, United States
University of Cincinnati Medical Center (UCMC)
🇺🇸Cincinnati, Ohio, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Maricopa Medical Center
🇺🇸Phoenix, Arizona, United States
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado Hospital
🇺🇸Denver, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Maryland, Baltimore
🇺🇸Baltimore, Maryland, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Capital Health System, Inc.
🇺🇸Trenton, New Jersey, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
John Peter Smith Health Network
🇺🇸Fort Worth, Texas, United States
CHU Dijon
🇫🇷Dijon, France
CHD Vendee
🇫🇷La Roche-sur-Yon, France
University of Kentucky
🇺🇸Lexington, Kentucky, United States
MUSC
🇺🇸Charleston, South Carolina, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States