Abstract: TH-PO1188
Phase 2 Trial of Phytonadione in Calciphylaxis
Session Information
- Late-Breaking Clinical Trials Posters
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- No subcategory defined
Author
- Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States
Group or Team Name
- On behalf of VitK-CUA trial investigators
Background
Calciphylaxis is a rare, life-threatening disorder characterized by calcific occlusion of cutaneous microvessels resulting in extremely painful skin lesions. There are no approved therapies for calciphylaxis and randomized controlled trials (RCTs) are lacking. Vitamin K deficiency is implicated in calciphylaxis via reducing gamma-carboxylation of matrix Gla protein (MGP)- a calcification inhibitor.
Methods
We performed a phase 2, double-blind, placebo-controlled trial of phytonadione (vitamin K1) in adult hemodialysis patients with calciphylaxis (NCT02278692) to examine pharmacodynamics (reduction in plasma uncarboxylated MGP levels), efficacy, and safety. Patients were randomly assigned to receive either oral phytonadione 10 mg or placebo thrice weekly for 12 weeks.
Results
Baseline characteristics and co-treatments were comparable between the two groups (N=26 patients [13 in each group]). The median change in uncarboxylated MGP level between baseline and 12-weeks was -1014 pmol/L (IQR: -1429 to -614 pmol/L) with phytonadione and 753 pmol/L (IQR: -315 to 1360 pmol/L) with placebo (p<0.001). Compared with placebo, treatment with phytonadione demonstrated greater improvements in the size of the largest skin lesion (p=0.02), the combined size of all lesions (p<0.001), and pain intensity (p<0.001). [Figure] The reduction in uncarboxylated MGP correlated with a reduction in the combined size of all lesions (r=0.56, p=0.01). At 12-weeks, mortality rates were 0% and 31% in phytonadione and placebo groups, respectively (p=0.03). One patient treated with phytonadione developed hepatic thrombosis.
Conclusion
In this phase 2 RCT of patients with calciphylaxis, oral phytonadione reduced uncarboxylated MGP and demonstrated clinical efficacy. A larger phase 3 study is now planned to establish the efficacy and safety of this agent in calciphylaxis.
Efficacy of phytonadione in calciphylaxis
Funding
- Other NIH Support