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
Affiliations
Anouk Pijpe
Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
Stephan G. Papendorp
Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
Joost W. van der Heijden
Department of Internal Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM Hoofddorp, The Netherlands
Ben Vermin
Department of Intensive Care Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM Hoofddorp, The Netherlands
Iris Ertugrul
Department of Intensive Care Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM Hoofddorp, The Netherlands
Michael W. J. Ritt
Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
Björn Stessel
Department of Intensive Care Medicine, Jessa Hospital, Stadsomvaart 11, 3500 Hasselt, Belgium
Ina Callebaut
Department of Intensive Care Medicine, Jessa Hospital, Stadsomvaart 11, 3500 Hasselt, Belgium
Albertus Beishuizen
Intensive Care Center, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ Enschede, The Netherlands
Marcel Vlig
Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ Beverwijk, The Netherlands
Joost Jimmink
Burn Centre, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
Henk J. Huijgen
Department of Clinical Chemistry, Red Cross Hospital, 1942 LE Beverwijk, The Netherlands
Paul P. M. van Zuijlen
Department of Plastic, Reconstructive and Hand Surgery, Amsterdam UMC Location Vrije Universiteit, Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Esther Middelkoop
Department of Plastic, Reconstructive and Hand Surgery, Amsterdam UMC Location Vrije Universiteit, Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Evelien de Jong
Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands
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.
