Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial

Anouk Pijpe, Stephan G. Papendorp, Joost W. van der Heijden, Ben Vermin, Iris Ertugrul, Michael W. J. Ritt, Björn Stessel, Ina Callebaut, Albertus Beishuizen, Marcel Vlig, Joost Jimmink, Henk J. Huijgen, Paul P. M. van Zuijlen, Esther Middelkoop, Evelien de Jong

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Background: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. Methods: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. Results: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. Conclusions: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.
Original languageEnglish
Article number723
Issue number4
Publication statusPublished - 1 Apr 2024


  • COVID-19
  • alkaline phosphatase
  • inflammatory response
  • mechanical ventilation

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