WASHINGTON — Results presented at ASN Kidney Week suggested phytonadione may be a safe and effective way to treat calciphylaxis in patients on hemodialysis.
“Calciphylaxis, which manifests with complicated skin wounds, is one of the most devastating conditions that affect dialysis patients,” Sagar U. Nigwekar, MD, MMSc, a nephrologist at Massachusetts General Hospital in Boston, told Healio Nephrology. “Once a patient develops this condition, there is a 60% to 70% chance that the individual will be dead within 1 year of follow-up. On top of the mortality, patients suffer from severe pain, frequent hospitalizations and infections. Although the condition has been described in medical literature for over 7 decades, there is no approved therapy.”
Nigwekar said previous studies have concluded that vitamin K deficiency predisposes these patients — who are also frequently on warfarin, a vitamin K antagonist — to the development of calciphylaxis. Thus, researchers sought to determine if they could supplement patients with high doses of vitamin K to “rescue” those who already have the condition. In what is the first phase two randomized clinical trial for calciphylaxis, 26 patients received either placebo or phytonadione (vitamin K1). Phytonadione was given at a dose of 10 mg three times per week after hemodialysis sessions. The study lasted for 12 weeks. Mortality rates were 0% for patients treated with phytonadione vs. 31% for those treated with placebo.
Researchers observed that oral phytonadione reduced plasma levels of matrix Gla protein (-1014 pmol/L vs. 753 pmol/L with placebo), while also improving skin lesion size. There were also greater improvements in pain intensity for patients taking phytonadione than placebo.
Nigwekar noted that although complications were rare (one patient taking phytonadione developed hepatic thrombosis), clinicians should be aware of this possibility.
“This is a very early study, primarily designed to look at feasibility and safety,” he concluded. “Still, we are pleased to see the efficacy of phytonadione and are planning a phase 3 trial.” – by Melissa J. Webb
Nigwekar SU, et al. Abstract TH-PO1188. Presented at: ASN Kidney Week; Nov. 7-10, 2019; Washington, D.C.
Disclosure: Nigwekar reports consulting for Epizon Pharmaceuticals.