(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI

Stopped early · Phase 3 · Has a placebo group

Conditions studied: Acute Kidney Injury Due to Sepsis

In brief

Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis. The study has three distinct SA-AKI trial populations: 1. The main trial population: Patients with a pre-AKI reference eGFR ≥45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 2. A 'moderate' CKD population: Patients with a pre-AKI reference eGFR ≥25 and \<45 mL/min/1.73 m2 and no proven or suspected SARS-CoV-2 at time of randomization. 3. A Corona Virus Disease 2019 (COVID-19) population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD. For patients in this population, COVID-19 should be the main cause of SA-AKI. In the main study population approximately 1400 patients will be enrolled and in the two cohorts with moderate CKD and COVID-19 each up to 100 patients. There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

Key facts

Study ID

NCT04411472

Run by

AM-Pharma

People needed

676

Starts

2020-11-02

Expected to finish

2022-08-18

Last updated by the study team

2024-06-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 18 years or older.
• In the ICU or intermediate care unit for clinical reasons.
• Have sepsis requiring vasopressor (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, or angiotensin II) therapy, i.e.:
• suspected or proven bacterial or viral infection. and
• on vasopressor therapy (≥0.1 µg/kg/min norepinephrine or equivalent) for sepsis-induced hypotension for at least one hour despite adequate fluid resuscitation according to clinical judgement. Following the initial one hour on at least 0.1 µg/kg/min norepinephrine or equivalent, any dose of vasopressor counts as vasopressor therapy.
• The combination of a) and b) automatically ensures that patients fulfill the Sepsis 3 criteria as 0.1 µg/kg/min norepinephrine corresponds to a score of +4 on the Cardiovascular sub-score of the SOFA score.
• Have AKI according to at least one of the below KDIGO criteria, a to d:
• An absolute increase in serum or plasma creatinine (CR) by ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours.
• or
• A relative increase in CR to ≥1.5 times the pre-AKI reference CR value which is known or presumed to have occurred within prior 7 days.
• or
• A decrease in urinary output to <0.5 mL/kg/hour for a minimum of 6 hours following adequate fluid resuscitation.
• or d) If the patient does not have a known history of CKD and there is no pre-AKI reference CR value available from the past 12 months available from the past 12 months: a CR value greater or equal to the levels presented in Table 1, with the increase in CR presumed to have occurred within prior 7 days.
• Provision of signed and dated ICF in accordance with local regulations.

You may not qualify if…

• a) At sites where enrolment of 'moderate' CKD patients is allowed, patients with 'severe' CKD defined as a pre-AKI reference eGFR <25 mL/min/1.73 m2 are excluded.
• For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as ≥25 mL/min/1.73 m2.
• For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 25-60 mL/min/1.73 m2 can also be used to rule out 'severe' CKD.
• b) At sites where enrolment of 'moderate' CKD patients is NOT allowed, patients with 'moderate' and 'severe' CKD defined as a pre-AKI reference eGFR <45 mL/min/1.73 m2 are excluded.
• For patients with known CKD, the most recent eGFR prior to index hospitalization needs to be documented as ≥45 mL/min/1.73 m2.
• For patients with known CKD but no known eGFR prior to hospitalization, presentation eGFR between 45-60 mL/min/1.73 m2 can also be used to rule out 'moderate' and 'severe' CKD.
• Advanced chronic liver disease, defined as a Child-Pugh score of 10 to 15 (Class C).
• Acute pancreatitis without proven infection.
• Urosepsis related to suspected or proven urinary tract obstruction.
• Main cause of AKI not sepsis.
• Proven or suspected SARS-CoV-2 infection. NOTE: This exclusion criterion does not apply to patients in the COVID-19 population, in which COVID-19 should be the main cause of SA-AKI.
• Severe burns requiring ICU treatment.
• Severely immunosuppressed, e.g. due to:
• hematopoietic cell transplantation within past 6 months prior to Screening or acute or chronic graft-versus-host disease
• solid organ transplantation
• leukopenia not related to sepsis, i.e., preceding sepsis
• Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS)
• receiving chemotherapy within 30 days prior to Screening.
• At high risk of being LTFU, e.g., due to known current or recent (within the last 6 months) IV drug abuse or known to be homeless.
• Limitations to use of mechanical ventilation (MV), RRT or vasopressors and inotropes (NOTE: limitation of cardiopulmonary resuscitation (CPR) only is not an exclusion criterion).
• Previous administration of recAP.
• Use of a non-marketed drug within the last month or concurrent or planned participation in a clinical trial for a non-marketed drug or device. (NOTE: Co-enrollment or concurrent participation in observational, non-interventional trials using no protocolized treatments or procedures are always allowed. Co-enrollment or concurrent participation in trials using protocolized treatments or procedures, e.g. blood draws, requires pre-approval by the TSC).
• Current or planned extracorporeal membrane oxygenation (ECMO).
• On RRT >24 hours before start of trial drug.
• No longer on vasopressor therapy at time of randomization.

Where it is running

• Ronald Reagan UCLA Medical Center — Los Angeles, California, United States
• The George Washington University Medical Faculty Associates - Anesthesiology — Washington D.C., District of Columbia, United States
• Emory Clinical Cardiovascular Research Institute — Atlanta, Georgia, United States
• Glenbrook Hospital — Glenview, Illinois, United States
• NorthShore Medical Group - Bannockburn — Highland Park, Illinois, United States
• University of Kentucky College of Medicine (UKCM) — Lexington, Kentucky, United States
• Regions Hospital — Saint Paul, Minnesota, United States
• University of New Mexico School of Medicine — Albuquerque, New Mexico, United States
• Wake Forest Baptist Medical Center — Winston-Salem, North Carolina, United States
• University of Cincinnati Cancer Institute — Cincinnati, Ohio, United States
• The Ohio State University - Dorothy M. Davis Heart and Lung Research Institute — Columbus, Ohio, United States
• UPMC CancerCenter at Magee - Womens Hospital — Pittsburgh, Pennsylvania, United States
• UPMC Presbyterian — Pittsburgh, Pennsylvania, United States
• University of Virginia Health System — Charlottesville, Virginia, United States
• Froedtert & the Medical College of Wisconsin Froedtert Hospital — Milwaukee, Wisconsin, United States
• Flinders Medical Centre — Bedford Park, Australia
• Bendigo Hospital — Bendigo, Australia
• Footscray Hospital — Footscray, Australia
• Austin Hospital — Melbourne, Australia
• John Hunter Hospital — New Lambton Heights, Australia
• Sunshine Hospital ICU - Western Hospital — Saint Albans, Australia
• Gold Coast University Hospital (GCUH) — Southport, Australia
• Medizinische Universitaet Graz - Klinik fuer Innere Medizin — Graz, Austria
• Medizinische Universitaet Innsbruck - Universitaetsklinik fuer Innere Medizin I — Innsbruck, Austria
• The University of Arizona Cancer Center — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.