(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI
Summary
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.
Timeline
- Start
- 2020-11-02
- Primary completion
- 2022-08-18
- Completion
- 2022-08-18
Outcome
Mixed primary results
Stopped: “The Data Monitoring Committee (DMC) concluded that the pre-specified futility threshold was met and that there was no safety concern.”
registry analysis (superiority test); Placebo vs recAP 1.6 mg/kg; p = 0.8025; Odds Ratio (OR) 1.18 (95% CI 0.805 to 1.732); One-sided p-value NCT04411472 ↗
registry analysis (superiority test); Placebo vs recAP 1.6 mg/kg; p = 0.1824; Odds Ratio (OR) 0.54 (95% CI 0.139 to 2.131); One-sided p-value NCT04411472 ↗
registry analysis (superiority test); Placebo vs recAP 1.6 mg/kg; p = 0.0080; Odds Ratio (OR) 0.02 (95% CI 0.001 to 0.405); One-sided p-value NCT04411472 ↗
Publications
- Results Pickkers P, Angus DC, Bass K, Bellomo R, van den Berg E, Bernholz J, Bestle MH, Doi K, Doig CJ, Ferrer R, Francois B, Gammelager H, Pedersen UG, Hoste E, Iversen S, Joannidis M, Kellum JA, Liu K, Meersch M, Mehta R, Millington S, Murray PT, Nichol A, Ostermann M, Pettila V, Solling C, Winkel M, Young PJ, Zarbock A; REVIVAL investigators. Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL). Intensive Care Med. 2024 Jan;50(1):68-78. doi: 10.1007/s00134-023-07271-w. Epub 2024 Jan 3.
- Results Pickkers P, Angus DC, Arend J, Bellomo R, van den Berg E, Bernholz J, Bestle M, Broglio K, Carlsen J, Doig CJ, Ferrer R, Joannidis M, Francois B, Doi K, Kellum JA, Laterre PF, Liu K, Mehta RL, Murray PT, Ostermann M, Pettila V, Richards S, Young P, Zarbock A, Kjolbye AL. Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury. BMJ Open. 2023 Apr 3;13(4):e065613. doi: 10.1136/bmjopen-2022-065613.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Recombinant Human Alkaline Phosphatase | Protein / enzyme biologic | 1.6 mg/kg | Intravenous |