Background and Rationale

Calciphylaxis is a rare but serious condition where deposits of calcium block blood supply to the skin, causing painful ulcers^[1]. It has no proven treatment options^[2,3]. It largely occurs in patients with kidney failure already experiencing high morbidity and has a poor prognosis, with a median survival time of three months and a mortality rate of up to 80% in the first 6-months following diagnosis^[1,3,4,5]. 

Evidence to guide calciphylaxis care is urgently needed. To date, no randomised controlled trials (RCTs) for calciphylaxis treatments have been completed and there is considerable variation in its clinical management both within and between countries. The lack of RCTs in part reflects the challenges associated with investigating a disease of its kind. These barriers include its low incidence; the lack of tolerance for prolonged placebo treatment; low tolerance for single active treatments in the face of no treatment response; the requirement for a biopsy-based diagnosis of calciphylaxis in current RCTs; the treatment of the disease typically involving multiple modalities of clinical care; and the lack of standardised methodology for assessing calciphylaxis outcomes in RCTs. The Better Evidence And Translation for Calciphylaxis (BEAT-Calci) trial has been developed to specifically address these barriers.

In this platform trial, multiple treatments across diverse domains of therapeutic care will be assessed within the same trial infrastructure. This provides the most efficient structure for evidence generation in a rare disease, whilst pre-specified adaptations in specific domains increase the chances that patients receive the most promising treatment in that domain. BEAT-Calci will initiate with following two active domains;