Acute kidney injury due to intra-abdominal infection/sepsis MedDRA version: 20.1 Level: LLT Classification code 10080269 Term: Stage 2 acute kidney injury System Organ Class: 100000004857 MedDRA version: 20.1 Level: LLT Classification code 10080271 Term: Stage 3 acute kidney injury System Organ Class: 100000004857 MedDRA version: 20.1 Level: LLT Classification code 10079983 Term: Complicated intra-abdominal infection System Organ Class: 100000004862 MedDRA version: 20.0 Level: LLT Classifica
Conditions
Interventions
Product Name: Reltecimod
Product Code: AB103
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: RELTECIMOD
Current Sponsor code: AB103
Concentration unit: mg/ml milligram(s)/m
Sponsors
Atox Bio
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Age: 18 up to and including 85 years 2 Has either suspected or confirmed diagnosis of abdominal sepsis requiring treatment with parenteral antibiotics and planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures within 24h of evaluation by medical personnel. Recommended surgical or interventional radiologic procedures be performed within 12h of evaluation by medical personnel • Suspected clinical diagnosis of abdominal infection as evaluated by the attending surgeon including any of the following clinical criteria: - Abdominal pain and/or tenderness - Localized or diffuse abdominal wall rigidity - Mass - Ileus AND - Any of the following radiologic findings • Free air • Intraabdominal abscess • Free peritoneal fluid • Confirmed diagnosis of abdominal infection by any of the of the following criteria: - Perforation and/or necrotic bowel with surgical confirmation of peritonitis - Presence of intraabdominal abscess by surgical confirmation or drainage of purulent fluid from interventional radiologic procedure 3 Planned or current admission to a hospital ward (preferably to an ICU but step down unit or equivalent or general ward are also considered eligible) 4 Initial diagnosis of AKI established either upon presentation to medical care at the study site 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. AKI Stage 2 or 3 according to the following KDIGO AKI criteria: • Stage 2 Increase in serum creatinine to > 200% (= 2.0–fold) from a reference creatinine value (see below) in the absence of primary underlying renal disease OR Urine output 300% (= 3.0–fold) from a reference creatinine value in the absence of primary underlying renal disease OR Serum creatinine =4 mg/dL OR Planned or initiation of RRT for acute AKI OR Urine output 2.0-fold) the normal creatinine value for age, race, and gender and a renal ultrasound or computed tomography showing normal kidney size within the past 90 days. Normal kidney size is defined as: o Renal Ultrasound • 10 cm length • >60 years if either kidney >9.5 cm length o Computed Tomographic Scan • If either kidney is >9 cm length 5 Study medication must be administered within 6 hours of confirmation of onset of Stage 2 or 3 AKI as established at the
Exclusion criteria
Exclusion criteria: 1. Has known prior history of CKD with a documented estimated GFR (eGFR) 50 mmHg and/or systolic blood pressure > 70 mmHg for at least 1 hour prior to dosing despite the presence of vasopressors and IV fluids or (b) a patient with respiratory failure such that an SaO2 of 80% for at least 1 hour prior to dosing cannot be achieved or (c) a patient with refractory coagulopathy (INR >5) or thrombocytopenia (platelet count <20,000) that does not partially correct for at least 1 hour prior to dosing with administration of appropriate factors or blood products 7. Severe neurological impairment due to cerebrovascular accident or cardiac arrest. 8. Recent cerebrovascular accident in the last 3 months. 9. Patients with cardiac arrest requiring cardiopulmonary resuscitation within the past 30 days. 10. Patient is not expected to survive throughout 28 days of study due to underlying medical condition, such as poorly controlled neoplasm (e.g. Stage III or IV cancer). 11. Classified as “Do Not Resuscitate”, or “Do Not Treat”, or the patient’s family is not committed to aggressive management of the patient’s condition. A “no cardiopulmonary resuscitation (CPR)” order is acceptable if the patient and/or the family are still committed to aggressive care short of CPR. 12. 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} • Very severe chronic obstructive pulmonary disease (COPD) {GOLD stage III-IV. or chronic hypoxemia (PaO2 <55 mmHg) on room air, or chronic use of home ventilation, or unable to climb stairs or perform household duties due to chronic obstructive disease resulting in severe exercise restriction, or use of continuous home oxygen prior to hospital admission (sleep apnoea treated with continuous positive airway pressure or biphasic positive airway pressure oxygen during sleep is acceptable)} • Liver dysfunction {Childs-Pugh class C} • Primary or acquired immunodeficiency or immunosuppression due to treatment with immunosuppressive medications (see Appendix G for list of excluded 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 che
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: • To compare the rates of complete recovery (alive, free of dialysis and return of serum creatinine to <150% of reference baseline; equivalent to acute kidney disease (AKD) category 0) at Day 14 between the Reltecimod-treated patients and the placebo-treated patients • To demonstrate the safety and tolerance of Reltecimod when administered as a single dose of 0.50 mg/kg to patients diagnosed with SA-AKI ;Secondary Objective: • To compare the rates of complete recovery at Day 28 between Reltecimod and placebo-treated patients • To compare the rates of overall recovery defined as complete recovery or partial recovery at Days 14 and 28, respectively between Reltecimod and placebo-treated patients • To compare time to complete recovery from AKI between the Reltecimod and placebo-treated patients • To compare time to overall recovery from AKI between the Reltecimod and placebo-treated patients • To compare the distributions of acute kidney disease stages at Days 14 and 28, respectively between Reltecimod and placebo-treated patients • To compare AKI-free days over 14 and 28 days between Reltecimod and placebo-treated patients • To compare the resolution of organ dysfunction between the Reltecimod and placebo-treated patients over time and at Day 14 (all secondary objectives are detailled in the study protocol) ;Primary end point(s): • To compare the rates of complete recovery (alive, free of dialysis and return of serum creatinine to <150% of reference baseline; equivalent to acute kidney disease (AKD) category 0) at Day 14 between the Reltecimod-treated patients and the placebo-treated patients;Timepoint(s) of evaluation of this end point: 14 Days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints have been specified from several domains including an endpoint similar to the primary endpoint but defined at Day 28. Additional secondary endpoints include evaluation of SOFA score over time;, time to complete renal recovery, time to at least partial renal recovery, critical care and hospital stay parameters (ICU and ICU-free days, ventilator days and –free days, vasopressor days and –free days,renal replacement days and-free days, hospital length of stay (LOS)). Analyses for these endpoints will generally be descriptive, with emphasis on characterizing clinical effect sizes. Nominal p-values will be presented. Categorical outcomes will be described using counts and percentages with nominal p-values determined through chi-square or exact methods. Critical care and hospital stay endpoints will be described using non-parametric approaches including using concordance statistics to characterize clinical effect sizes and Wilcoxon rank sum tests to determine nominal statistical significance. Methods appropriate for time-to-event endpoints including survival and life-table methods will be used for time-to-recovery endpoints.;Timepoint(s) of evaluation of this end point: Variable | — |
Countries
Belgium, France, Netherlands, United States
Contacts
Public ContactClinical Trial Operations Manager
Centre Hospitalier Universitaire de Limoges
Outcome results
None listed