Phase 2 randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of Reltecimod as compared to placebo in addition to standard of care in patients with sepsis-associated acute kidney injury (SA-AKI)
- Conditions
- blood poisoning-associated acute kidney injurySepsis-associated acute kidney injury10038430
- Registration Number
- NL-OMON48294
- Lead Sponsor
- Atox Bio Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 12
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 24
hours of evaluation by medical personnel. Recommended surgical or
interventional radiologic procedures be performed with 12 hours 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 (Plain film, CT or MRI scans)
* Intraabdominal abscess (Ultrasound, CT or MRI scans)
* Free peritoneal fluid (Ultrasound, CT or MRI scans)
* 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. Age: 18 up to and including 85 years
4. 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 24
hours of evaluation by medical personnel. Recommended surgical or
interventional radiologic procedures be performed with 12 hours 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 (Plain film, CT or MRI scans)
* Intraabdominal abscess (Ultrasound, CT or MRI scans)
* Free peritoneal fluid (Ultrasound, CT or MRI scans)
* 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
5. Planned or current admission to a hospital ward (preferably to an ICU but
patients admitted to a step down unit (or equivalent) or general ward are also
considered eligible)
6. 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 AKI
- Increase in serum creatinine to > 200% (* 2.0*fold) from a reference
creatinine value (see below) in the absence of primary underlying renal disease
(eGFR>30 ml/min)
OR
- Urine output < 0.5ml/kg/hr x 12 hours following adequate fluid resuscitation
[the aggregate over any 12-hour period can be used with hourly rate being
relatively persistent over the 12-hour period]
- Urine output should be calc
1. Has known prior history of CKD with a documented estimated GFR (eGFR) < 30
mL/min by a commonly used formula such as Modification of Diet in Renal Disease
(MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or known
GFR < 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 (normal size
defined above) evaluation (performed within 90 days of screening) will be
eligible
2. Patients receiving RRT for chronic kidney disease: either hemodialysis,
peritoneal dialysis, hemofiltration such as Continuous Veno-Venous
Hemofiltration (CVVH) or hemodiafiltration.
3. Removed
4. Previously diagnosed with documented AKI in the last 30 days
5. Documented primary glomerular disease or toxic tubulo-interstitial nephritis
or other underlying renal diseases significantly effecting renal function
(e.g., renal amyloidosis, polycystic kidney disease, renal cancer, renal
abscess) at the time of AKI diagnosis
6. 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
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 IV 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 chemotherapy or biologic anti¬cancer treatmen
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objective:<br /><br>* To compare the rates of complete recovery (alive, free of dialysis and return<br /><br>of serum creatinine to <150% of reference baseline; equivalent to acute kidney<br /><br>disease (AKD) category 0) at Day 14 between the Reltecimod-treated patients and<br /><br>the placebo-treated patients<br /><br>* To demonstrate the safety and tolerance of Reltecimod when administered as a<br /><br>single dose of 0.50 mg/kg to patients diagnosed with SA-AKI</p><br>
- Secondary Outcome Measures
Name Time Method