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

被引:0
|
作者
Pijpe, Anouk [1 ,2 ,3 ,4 ,5 ]
Papendorp, Stephan G. [1 ,5 ]
van der Heijden, Joost W. [6 ]
Vermin, Ben [7 ]
Ertugrul, Iris [7 ]
Ritt, Michael W. J. [1 ]
Stessel, Bjorn [8 ,9 ]
Callebaut, Ina [8 ,9 ]
Beishuizen, Albertus [10 ]
Vlig, Marcel [4 ]
Jimmink, Joost [5 ]
Huijgen, Henk J. [11 ]
van Zuijlen, Paul P. M. [2 ,3 ,5 ,12 ,13 ]
Middelkoop, Esther [2 ,3 ,4 ,5 ]
de Jong, Evelien [1 ,5 ]
机构
[1] Red Cross Hosp, Dept Intens Care, Vondellaan 13, NL-1942 LE Beverwijk, Netherlands
[2] Amsterdam UMC Locat Vrije Univ, Dept Plast Reconstruct & Hand Surg, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands
[3] Amsterdam Movement Sci Tissue Funct & Regenerat, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands
[4] Assoc Dutch Burn Ctr, Zeestraat 27-29, NL-1941 AJ Beverwijk, Netherlands
[5] Red Cross Hosp, Burn Ctr, Vondellaan 13, NL-1942 LE Beverwijk, Netherlands
[6] Dept Internal Med, Spaarne Gasthuis, Spaarnepoort 1, NL-2134 TM Hoofddorp, Netherlands
[7] Dept Intens Care Med, Spaarne Gasthuis, Spaarnepoort 1, NL-2134 TM Hoofddorp, Netherlands
[8] Jessa Hosp, Dept Intens Care Med, Stadsomvaart 11, B-3500 Hasselt, Belgium
[9] Univ Hasselt, Fac Med & Life Sci, LCRC, B-3590 Diepenbeek, Belgium
[10] Intens Care Ctr, Med Spectrum Twente, Koningsplein 1, NL-7512 KZ Enschede, Netherlands
[11] Red Cross Hosp, Dept Clin Chem, NL-1942 LE Beverwijk, Netherlands
[12] Red Cross Hosp, Dept Plast Reconstruct & Hand Surg, Vondellaan 13, NL-1942 LE Beverwijk, Netherlands
[13] Emma Childrens Hosp, Pediat Surg Ctr, Amsterdam UMC Locat Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands
关键词
alkaline phosphatase; COVID-19; mechanical ventilation; inflammatory response; ENDOTOXIN;
D O I
10.3390/biomedicines12040723
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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