The primary objective of the Dialysis Membrane Domain is to investigate whether treatment with medium cut-off haemodialysis is superior to high flux haemodialysis in improving outcomes measured on the BEAT-Calci Wound Assessment Scale, in patients with kidney failure and newly diagnosed calciphylaxis.
High flux haemodialysis (HD) is the standard dialysis therapy used in centres worldwide. In this domain, treatment with HD is the control arm.
Medium cut-off haemodialysis (MCO HD) uses the medium cut-off (MCO) dialyser which has a pore size between those of a standard high-flux dialyser and a high cut-off dialyser. MCO HD therapy allows clearance and subsequent reduction of larger middle molecules which may play a crucial role in stopping or limiting the inflammatory and calcification processes in calciphylaxis. In this domain, treatment with MCO HD is the intervention arm.
The primary objective of the Pharmacotherapy Domain is to investigate whether treatment with any of the active interventions within the domain are superior to placebo in improving outcomes measured on the BEAT-Calci Wound Assessment Scale, in patients with kidney failure and newly diagnosed calciphylaxis.
Within this domain, Sodium Thiosulfate, Vitamin K1 and Magnesium Citrate will be compared to each other and to matched placebo.
The exact mechanism of action of Sodium Thiosulfate is unclear but may include antioxidant and anti-inflammatory actions on the endothelium, vasodilation or calcium-chelation. The intervention being tested in this domain is Sodium Thiosulfate intravenous injections.
Supplementation with Vitamin K1 may protect against vascular calcification through its role in the carboxylation of Matrix Gla protein (MGP) as carboxylated Matrix Gla Protein (cMGP) is a potent inhibitor of vascular calcification. The intervention being tested in this domain is Vitamin K1 capsules.
Supplementation with Magnesium Citrate may protect against vascular calcification through various pathways and may also reduce pain. The intervention being tested in this domain is Magnesium Citrate tablets.