Better Evidence and Translation for Calciphylaxis (BEAT-Calci)

This global platform study will evaluate multiple interventions, across several domains of therapeutic care, in adult patients with kidney failure and newly diagnosed calciphylaxis.

Study Overview

• Status: Recruiting
• Conditions: Calciphylaxis
• Intervention / Treatment: Drug: Placebo injection (normal saline); Drug: Placebo capsule (Vitamin K1); Drug: Placebo tablet (Magnesium citrate); Drug: Vitamin K1; Drug: Magnesium citrate; Drug: Sodium Thiosulfate; Device: High Flux Dialyser; Device: Medium Cut-off Dialyser

Detailed Description

BEAT-Calci is a randomized, adaptive, multi-center, platform trial that will evaluate multiple interventions, across several domains of therapeutic care. The objective of the study is to establish high-quality evidence on the effect of a range of interventions in patients with kidney failure and newly diagnosed calciphylaxis. Calciphylaxis is a rare disease affecting 1-2 people in 10,000.

The trial will commence with a Dialysis Membrane Domain and Pharmacotherapy Domain. The Pharmacotherapy Domain of BEAT-Calci is a placebo-controlled, double blind, response adaptive, randomised controlled trial that will investigate whether any of the pharmacotherapeutic agents is superior to placebo in improving outcomes. The Dialysis Membrane Domain of BEAT-Calci is an open-label, randomised controlled two-way comparison between two different dialysis technologies.

The BEAT-Calci Wound Assessment Scale (BCWAS) is the primary endpoint for the trial. It is an 8-point ordinal categorical scale of disease outcomes and will be used to determine each participant's outcome.

The trial will utilise a Bayesian adaptive sample size re-estimation approach for sample size calculations. The trial will continue to recruit until predefined superiority or futility rules are met. As the trial progresses, in response to information accumulating during the trial, there are various adaptations that can occur, including addition or removal of an intervention arm, response adaptive randomisation and addition of new therapeutic domains.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sibyl Masterman; Phone Number: 8036 5272; Email: sibyl.masterman@sydney.edu.au
• Study Contact Backup: Name: Meg Jardine; Phone Number: 9562 5000; Email: meg.jardine@sydney.edu.au

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Royal Adelaide Hospital
    • Contact: Michael Collins
  • Clayton, Australia
    • Recruiting
    • Monash Medical Centre
    • Contact: Peter Kerr
  • New South Wales
    • Concord, New South Wales, Australia
      • Recruiting
      • Concord Repatriation General Hospital
      • Contact: Angus Ritchie
    • Kogarah, New South Wales, Australia
      • Recruiting
      • St George Hospital
      • Contact: Brendan Smyth
  • Queensland
    • Birtinya, Queensland, Australia
      • Recruiting
      • Sunshine Coast Hospital and Health Service
      • Contact: Rathika Krishnasamy
    • Brisbane, Queensland, Australia
      • Recruiting
      • Princess Alexandra Hospital
      • Contact: Carmel Hawley
    • Bundaberg, Queensland, Australia
      • Recruiting
      • Bundaberg Base Hospital
      • Contact: Clyson Mutatiri
  • Victoria
    • Melbourne, Victoria, Australia
      • Recruiting
      • Royal Melbourne Hospital
      • Contact: Irene Ruderman
    • St Albans, Victoria, Australia
      • Recruiting
      • Sunshine Hospital (Western Health)
      • Contact: Eugenia Pedagogos
• New Zealand
  • Dunedin, New Zealand
    • Recruiting
    • Dunedin Hospital
    • Contact: Rob Walker
  • Grafton, New Zealand
    • Recruiting
    • Auckland City Hospital (Auckland DHB)
    • Contact: Tze Goh
  • Takapuna, New Zealand
    • Recruiting
    • North Shore Hospital (Waitemata DHB)
    • Contact: Janak de Zoysa
  • Tauranga, New Zealand
    • Recruiting
    • Tauranga Hospital
    • Contact: Gavin McHaffie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Currently receiving haemodialysis, or peritoneal dialysis that can be converted to haemodialysis, with planned ongoing haemodialysis a minimum of three times per week for at least the duration of the protocolised calciphylaxis treatments within this trial
2. Have a new calciphylaxis ulcer present for less than 10 weeks
3. Age ≥ 18 years
4. Eligible for randomisation in at least one recruiting domain
5. The participant and treating physician are willing and able to perform trial procedures

Exclusion Criteria:

Nil

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Double-Blind Period); Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate	Drug: Placebo injection (normal saline); Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.; Other Names: 0.9% sodium chloride solution; Drug: Placebo capsule (Vitamin K1); Placebo to be administered 3 times per week following the subject's hemodialysis session.; Other Names: Matching placebo capsule; Drug: Placebo tablet (Magnesium citrate); Placebo to be administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.; Other Names: Matching placebo tablet
Experimental: Vitamin K1 (Double-Blind Period); Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session.; Placebo Magnesium Citrate; Placebo Sodium Thiosulphate	Drug: Placebo injection (normal saline); Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.; Other Names: 0.9% sodium chloride solution; Drug: Placebo tablet (Magnesium citrate); Placebo to be administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.; Other Names: Matching placebo tablet; Drug: Vitamin K1; Vitamin K1 capsule (10mg) to be administered 3 times per week following the subject's hemodialysis session.; Other Names: Phytonadione
Experimental: Magnesium Citrate (Double-Blind Period); Dose: 150mg Magnesium Citrate tablets, administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.; Placebo Vitamin K1; Placebo Sodium Thiosulphate	Drug: Placebo injection (normal saline); Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.; Other Names: 0.9% sodium chloride solution; Drug: Placebo capsule (Vitamin K1); Placebo to be administered 3 times per week following the subject's hemodialysis session.; Other Names: Matching placebo capsule; Drug: Magnesium citrate; Magnesium Citrate tablet (150mg) to be administered 3 times per per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.
Experimental: Sodium Thiosulfate (Double-Blind Period); Dose: 25g Sodium Thiosulfate injection, administered intravenously 3 times per week, during the subject's last hour of hemodialysis.; Placebo Vitamin K1; Placebo Magnesium Citrate	Drug: Placebo capsule (Vitamin K1); Placebo to be administered 3 times per week following the subject's hemodialysis session.; Other Names: Matching placebo capsule; Drug: Placebo tablet (Magnesium citrate); Placebo to be administered 3 times per day. On dialysis days, administration of the middle daily dose should occur following the subject's hemodialysis session.; Other Names: Matching placebo tablet; Drug: Sodium Thiosulfate; Sodium Thiosulfate injection (25g/100ml) to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.; Other Names: Intravenous Sodium Thiosulfate Injection
Active Comparator: High Flux Hemodialysis; Hemodialysis using a high flux dialyser	Device: High Flux Dialyser; Hemodialysis using a high flux dialyser.; Other Names: High Flux Hemodialysis
Experimental: Medium Cut-off Hemodialysis; Hemodialysis using a medium cut-off dialyser	Device: Medium Cut-off Dialyser; Hemodialysis using a medium cut-off dialyser.; Other Names: Medium Cut-off Hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BEAT-Calci Wound Assessment Scale (BCWAS) - Baseline to Week 12	To determine whether addition of the intervention changes the sentinel ulcer from Baseline to Week 12 on the BEAT-Calci Wound Assessment Scale. This is an 8-point ordinal categorical scale of change since baseline, which will be used to determine each participant's outcome. The scale is described as: Complete epithelialisation of the sentinel ulcer; >50% reduction in sentinel ulcer surface area; 20-50% reduction in sentinel ulcer surface area; 0-20% reduction in sentinel ulcer surface area; Any increase in sentinel ulcer surface area; Development of new ulcers; Amputation due to an ulcer; All-cause death	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BEAT-Calci Wound Assessment Scale - Baseline to Week 26	To determine whether addition of the intervention changes the sentinel ulcer from Baseline to Week 26 on the BEAT-Calci Wound Assessment Scale. This is an 8-point ordinal categorical scale of change since baseline, which will be used to determine each participant's outcome. The scale is described as: Complete epithelialisation of the sentinel ulcer; >50% reduction in sentinel ulcer surface area; 20-50% reduction in sentinel ulcer surface area; 0-20% reduction in sentinel ulcer surface area; Any increase in sentinel ulcer surface area; Development of new ulcers; Amputation due to an ulcer; All-cause death	Week 26
Distribution of each of the individual components of the BCWAS, assessed at Weeks 4	To determine whether addition of the intervention changes the distribution of each of the individual components of the BEAT-Calci Wound Assessment Scale, assessed at Weeks 4 Scale described as: Complete epithelialisation of the sentinel ulcer; >50% reduction in sentinel ulcer surface area; 20-50% reduction in sentinel ulcer surface area; 0-20% reduction in sentinel ulcer surface area; Any increase in sentinel ulcer surface area; Development of new ulcers; Amputation due to an ulcer; All-cause death	Week 4
Distribution of each of the individual components of the BCWAS, assessed at Week 12	To determine whether addition of the intervention changes the distribution of each of the individual components of the BEAT-Calci Wound Assessment Scale, assessed at Week 12 Scale described as: Complete epithelialisation of the sentinel ulcer; >50% reduction in sentinel ulcer surface area; 20-50% reduction in sentinel ulcer surface area; 0-20% reduction in sentinel ulcer surface area; Any increase in sentinel ulcer surface area; Development of new ulcers; Amputation due to an ulcer; All-cause death	Week 12
Distribution of each of the individual components of the BCWAS, assessed at Week 26	To determine whether addition of the intervention changes the distribution of each of the individual components of the BEAT-Calci Wound Assessment Scale, assessed at Week 26. Scale described as: Complete epithelialisation of the sentinel ulcer; >50% reduction in sentinel ulcer surface area; 20-50% reduction in sentinel ulcer surface area; 0-20% reduction in sentinel ulcer surface area; Any increase in sentinel ulcer surface area; Development of new ulcers; Amputation due to an ulcer; All-cause death	Week 26
Bates-Jensen Wound Assessment Tool - from Baseline to Week 4	To determine whether addition of the intervention changes the severity of sentinel ulcer from Baseline, assessed at Week 4 using the Bates-Jensen Wound Assessment Tool	Week 4
Bates-Jensen Wound Assessment Tool - from Baseline to Week 12	To determine whether addition of the intervention changes the severity of sentinel ulcer from Baseline, assessed at Week 12, using the Bates-Jensen Wound Assessment Tool	Week 12
Bates-Jensen Wound Assessment Tool - from Baseline to Week 26	To determine whether addition of the intervention changes the severity of sentinel ulcer from Baseline, assessed at Week 26, using the Bates-Jensen Wound Assessment Tool	Week 26
Sentinel ulcer surface area - from Baseline, assessed at Week 4	To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 4	Week 4
Sentinel ulcer surface area - from Baseline, assessed at Week 12	To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 12	Week 12
Sentinel ulcer surface area - from Baseline, assessed at Week 26	To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 26	Week 26
All ulcers total surface area - from Baseline, assessed at Week 4	To determine whether addition of the intervention changes the total surface area of all ulcers (not only the sentinel ulcer) from Baseline, assessed at Week 4	Week 4
All ulcers total surface area - from Baseline, assessed at Week 12	To determine whether addition of the intervention changes the total surface area of all ulcers (not only the sentinel ulcer) from Baseline, assessed at Week 12	Week 12
All ulcers total surface area - from Baseline, assessed at Week 26	To determine whether addition of the intervention changes the total surface area of all ulcers (not only the sentinel ulcer) from Baseline, assessed at Week 26	Week 26
Change over time of self-reported pain	To determine whether addition of the intervention changes self-reported pain over time, assessed using the 0-to-10 Numerical Rating Scale	Week 26
Self-reported pain at week 12	To determine whether addition of the intervention changes self-reported pain use at week 12 assessed using the 0-to-10 Numerical Rating Scale	Week 12
Change over time of analgesic use	To determine whether addition of the intervention changes analgesic use over time, as measured by cumulative weighted analgesia dose from baseline to week 26	Week 26
Analgesic use week 12	To determine whether addition of the intervention changes analgesic use over time, as measured by cumulative weighted analgesia dose from baseline to week 12	Week 12
Composite self-reported pain and analgesic use over time	To determine whether addition of the intervention changes the composite outcome of self-reported pain (assessed using the 0-to-10 Numerical Rating Scale) and analgesic use over time	Week 26
Composite self-reported pain and analgesic use at week 12	To determine whether addition of the intervention changes the composite outcome of self-reported pain (assessed using the 0-to-10 Numerical Rating Scale) and analgesic use at week 12	Week 12
Change in self-reported quality of life from Baseline to Week 4	To determine whether addition of the intervention changes self-reported quality of life from Baseline, assessed at Week 4, using the EuroQoL EQ-5D-5L instrument	Week 4
Change in self-reported quality of life from Baseline to Week 12	To determine whether addition of the intervention changes self-reported quality of life from Baseline, assessed at Week 12, using the EuroQoL EQ-5D-5L instrument	Week 12
Change in self-reported quality of life from Baseline to Week 26	To determine whether addition of the intervention changes self-reported quality of life from Baseline, assessed at Week 26 using the EuroQoL EQ-5D-5L instrument	Week 26
Time to first calciphylaxis-attributable infection from Baseline to Week 26	Time in days to first calciphylaxis-attributable infection within 26 weeks post-randomisation	Week 26
All-cause hospitalisation days	Count of all cause hospitalisation days (excluding day admissions for dialysis treatment within 26 weeks post-randomisation	Weeks 0-26
Mortality	Incidence of mortality, as derived from hospital reports, within 5-years post-randomisation	Up to 5 years
Kidney Transplantation	Incidence of kidney transplantation, as derived from hospital reports, within 5-years post-randomisation	Up to 5 years
Calciphylaxis recurrence	Incidence of calciphylaxis recurrence as derived from hospital reports, within 5-years post-randomisation	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Sydney
• Collaborators: Northern Care Alliance NHS Foundation Trust; Waitemata District Health Board; Australasian Kidney Trials Network
• Investigators: Study Chair: Meg Jardine, University of Sydney

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Calcium Metabolism Disorders; Calcinosis; Calciphylaxis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Fibrin Modulating Agents; Gastrointestinal Agents; Protective Agents; Micronutrients; Anti-Bacterial Agents; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Cathartics; Calcium Chelating Agents; Vitamin K; Vitamins; Citric Acid; Sodium Citrate; Sodium thiosulfate; Magnesium citrate; Vitamin K 1
• Other Study ID Numbers: BEAT-Calci

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Trial data will be disseminated in the form of a publication to a relevant clinical journal and presentation at appropriate scientific conferences.

Individual participant data that underlie the results reported, after de-identification (text, tables, figures, and appendices), may be shared with Investigators whose proposed use of the data has been approved by a review committee identified for this purpose.

• IPD Sharing Time Frame: To be confirmed
• IPD Sharing Access Criteria: No data should be released that would compromise the trial, unless specifically for safety reasons.; There must be a strong scientific or other legitimate rationale for the data to be used for the requested purpose.; Investigators should have a period of exclusivity in which to pursue their aims with the data, before key trial data are made available to other researchers.; Adequate resources must be available in order to comply with the request, and the scientific aims of the study must justify the use of such resources.; Data release complies with the relevant regulations from all relevant countries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No