(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI
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|ClinicalTrials.gov Identifier: NCT04411472|
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : November 4, 2020
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:
- 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.
- 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.
- A COVID-19 population: Patients with proven or suspected SARS-CoV-2 at time of randomization with or without 'moderate' CKD.
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Kidney Injury Due to Sepsis||Biological: Recombinant human alkaline phosphatase Other: Placebo||Phase 3|
Sepsis is the leading cause of acute kidney injury (AKI) and a major cause of death. Patients with SA-AKI have a high mortality and morbidity and are at risk of developing chronic kidney disease. AP is a homodimeric endogenous enzyme present in many cells and organs, e.g., intestines, placenta, liver, bone, kidney, and granulocytes. It exerts detoxifying effects through dephosphorylation of endotoxins; pathogen associated molecular pattern molecules (PAMPS e.g., lipopolysaccharide) and damage-associated molecular pattern molecules (DAMPS e.g., adenosine tri- and di-phosphate). In animal models of sepsis and AKI, administration of AP attenuates the inflammatory response, improves renal function and/or reduces mortality.
AM-Pharma B.V. is developing AP as a novel, recombinant chimeric human AP medicinal product, called recAP, to be used as an intravenous infusion for the treatment of SA-AKI. In the Phase 2 trial STOP-AKI, a survival benefit was observed in the two highest dose groups, 0.8 mg/kg and 1.6 mg/kg groups, compared to the placebo group. There were no safety or tolerability concerns for any of the doses tested (0.4, 0.8 and 1.6 mg/kg). The 1.6 mg/kg recAP dose was selected for this Phase 3 trial based on the significant survival benefit observed. PK/PD simulations also confirmed this dose to have the most pronounced treatment effect.
The primary objective of this Phase 3 trial is to confirm the mortality benefit seen in STOP-AKI by demonstrating a reduction in 28 day all cause mortality in patients with SA-AKI treated with 1.6 mg/kg recAP.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1600 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI|
|Actual Study Start Date :||November 2, 2020|
|Estimated Primary Completion Date :||August 15, 2023|
|Estimated Study Completion Date :||February 15, 2024|
recombinant human alkaline phosphatase 1.6mg/kg 3 daily 1 hour infusions
Biological: Recombinant human alkaline phosphatase
patients with SA-AKI are randomly assigned in a 1:1 ratio to either placebo or 1.6 mg/kg recAP.
Placebo Comparator: placebo
- 28-day all-cause mortality [ Time Frame: 28 days ]To demonstrate an effect of recAP on 28 day all cause mortality
- To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE). [ Time Frame: 90 Days ]MAKE 90: dead or on RRT or ≥25% decline in estimated glomerular filtration rate (eGFR) on Day 90 relative to the known or assumed pre-AKI reference level.
- To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors or inotropes. [ Time Frame: 28 days ]Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days).
- To investigate the effect of recAP on length of stay (LOS) in ICU. [ Time Frame: 28 days ]Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).
- To investigate the effect of recAP on 90-day allcause mortality [ Time Frame: 90 days ]Time to death through Day 90.
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 ClinicalTrials.gov identifier (NCT number): NCT04411472
|Contact: Annelies Legtersfirstname.lastname@example.org|
|Contact: Kristie Bassemail@example.com|
|Jeroen Bosch Ziekenhuis lokatie GZG||Recruiting|
|Contact: F.W. Rozendaal, MD W.Rozendaal@jbz.nl|
|Principal Investigator: F.W. Rozendaal, MD|
|Study Director:||Annelies Legters||AM-Pharma|