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

Anouk Pijpe ^1,2,3,4,5, Stephan G Papendorp ^1,5, Joost W van der Heijden ⁶

¹Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands.
²Department of Plastic, Reconstructive and Hand Surgery, Amsterdam UMC Location Vrije Universiteit, Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
³Amsterdam Movement Sciences, Tissue Function and Regeneration, Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
⁴Association of Dutch Burn Centres, Zeestraat 27-29, 1941 AJ Beverwijk, The Netherlands.
⁵Burn Centre, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands.
⁶Department of Internal Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM Hoofddorp, The Netherlands.
⁷Department of Intensive Care Medicine, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM Hoofddorp, The Netherlands.
⁸Department of Intensive Care Medicine, Jessa Hospital, Stadsomvaart 11, 3500 Hasselt, Belgium.
⁹LCRC, Faculty of Medicine and Life Sciences, University Hasselt, Agoralaan, 3590 Diepenbeek, Belgium.
¹⁰Intensive Care Center, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ Enschede, The Netherlands.
¹¹Department of Clinical Chemistry, Red Cross Hospital, 1942 LE Beverwijk, The Netherlands.
¹²Department of Plastic Reconstructive and Hand Surgery, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands.
¹³Emma Children's Hospital, Pediatric Surgical Center, Amsterdam UMC Location Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

⁰Department of Intensive Care, Red Cross Hospital, Vondellaan 13, 1942 LE Beverwijk, The Netherlands.

Biomedicines +

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April 27, 2024

View abstract on PubMed

Summary

Alkaline phosphatase (AP) therapy did not improve outcomes for hospitalized COVID-19 patients in the ICU. This randomized trial found no significant difference in mechanical ventilation duration or mortality between AP and placebo groups.

Area Of Science

Critical care medicine
Pharmacology
Infectious diseases

Background

Ongoing search for effective COVID-19 treatments for hospitalized patients.
Alkaline phosphatase (AP) converts pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine.

Purpose Of The Study

To evaluate the safety and efficacy of AP in ICU patients with SARS-CoV-2 infection.

Main Methods

Randomized controlled trial comparing AP versus placebo for four days in ICU patients.
Primary outcome: duration of mechanical ventilation.
Secondary outcomes: 28-day mortality, acute kidney injury, reintubation, safety, and inflammatory markers.

Main Results

Trial terminated early due to futility; 97 patients included (51 received AP).
AP did not significantly alter mechanical ventilation duration (9.0 vs 9.3 days, p=1.0).
No significant differences in 28-day mortality (18% AP vs 13% placebo, p=0.531) or other secondary outcomes; no safety concerns.

Conclusions

Alkaline phosphatase therapy demonstrated no significant clinical benefits for COVID-19 patients admitted to the ICU.

Keywords:

COVID-19 alkaline phosphatase inflammatory response mechanical ventilation