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Better Evidence and Translation for Calciphylaxis (BEAT-Calci)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05018221
Recruitment Status : Recruiting
First Posted : August 24, 2021
Last Update Posted : December 5, 2023
Sponsor:
Collaborators:
Australasian Kidney Trials Network
Northern Care Alliance NHS Foundation Trust
Waitemata District Health Board
Information provided by (Responsible Party):
University of Sydney

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

Condition or disease Intervention/treatment Phase
Calciphylaxis Drug: Vitamin K1 Drug: Magnesium citrate Drug: Sodium Thiosulfate Device: High Flux Dialyser Device: Medium Cut-off Dialyser Drug: Placebo injection (normal saline) Drug: Placebo capsule (Vitamin K1) Drug: Placebo tablet (Magnesium citrate) Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Adaptive, platform, randomized controlled trial, involving multiple interventions spanning several domains of therapeutic care.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Blinding of all parties will not be possible for all domains. The default position of the BEAT-Calci platform is that treatments determined by randomization will be blinded to as high a level is feasible.

Within practical domains, a blind will be adopted, whereby participants, site personnel, trial investigators and outcome assessors will remain blinded to the treatment from the time of randomization until database lock of the comparisons to which that participant is contributing data. In blinded domains, randomization data will not be accessible by anyone else involved in the trial with the following exceptions: (1) data managers who work on the randomization and drug management system, (2) unblinded statistician(s) involved with the response adaptive randomization, and (3) the unblinded biostatistician who prepares reports for the IDMC. Information on the blind, or lack thereof, per domain will be described in the respective Domain-Specific Appendix.
Primary Purpose: Treatment
Official Title: Better Evidence and Translation for Calciphylaxis
Actual Study Start Date : August 26, 2021
Estimated Primary Completion Date : December 2029
Estimated Study Completion Date : December 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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: Vitamin K1
Vitamin K1 capsule (10mg) to be administered 3 times per week following the subject's hemodialysis session.
Other Name: Phytonadione

Drug: Placebo injection (normal saline)
Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
Other Name: 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 Name: Matching placebo tablet
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: 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.

Drug: Placebo injection (normal saline)
Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
Other Name: 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 Name: Matching placebo capsule
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: Sodium Thiosulfate
Sodium Thiosulfate injection (25g/100ml) to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
Other Name: Intravenous Sodium Thiosulfate Injection

Drug: Placebo capsule (Vitamin K1)
Placebo to be administered 3 times per week following the subject's hemodialysis session.
Other Name: 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 Name: Matching placebo tablet
Active Comparator: High Flux Hemodialysis
Hemodialysis using a high flux dialyser
 Device: High Flux Dialyser
Hemodialysis using a high flux dialyser.
Other Name: 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 Name: Medium Cut-off Hemodialysis


Outcome Measures
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Primary Outcome Measures :
  1. BEAT-Calci Wound Assessment Scale (BCWAS) - Baseline to Week 12 [ Time Frame: 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:

    1. Complete epithelialisation of the sentinel ulcer
    2. >50% reduction in sentinel ulcer surface area
    3. 20-50% reduction in sentinel ulcer surface area
    4. 0-20% reduction in sentinel ulcer surface area
    5. Any increase in sentinel ulcer surface area
    6. Development of new ulcers
    7. Amputation due to an ulcer
    8. All-cause death


Secondary Outcome Measures :
  1. BEAT-Calci Wound Assessment Scale - Baseline to Week 26 [ Time Frame: 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:

    1. Complete epithelialisation of the sentinel ulcer
    2. >50% reduction in sentinel ulcer surface area
    3. 20-50% reduction in sentinel ulcer surface area
    4. 0-20% reduction in sentinel ulcer surface area
    5. Any increase in sentinel ulcer surface area
    6. Development of new ulcers
    7. Amputation due to an ulcer
    8. All-cause death

  2. Distribution of each of the individual components of the BCWAS, assessed at Weeks 4 [ Time Frame: Week 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:

    1. Complete epithelialisation of the sentinel ulcer
    2. >50% reduction in sentinel ulcer surface area
    3. 20-50% reduction in sentinel ulcer surface area
    4. 0-20% reduction in sentinel ulcer surface area
    5. Any increase in sentinel ulcer surface area
    6. Development of new ulcers
    7. Amputation due to an ulcer
    8. All-cause death

  3. Distribution of each of the individual components of the BCWAS, assessed at Week 12 [ Time Frame: 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:

    1. Complete epithelialisation of the sentinel ulcer
    2. >50% reduction in sentinel ulcer surface area
    3. 20-50% reduction in sentinel ulcer surface area
    4. 0-20% reduction in sentinel ulcer surface area
    5. Any increase in sentinel ulcer surface area
    6. Development of new ulcers
    7. Amputation due to an ulcer
    8. All-cause death

  4. Distribution of each of the individual components of the BCWAS, assessed at Week 26 [ Time Frame: 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:

    1. Complete epithelialisation of the sentinel ulcer
    2. >50% reduction in sentinel ulcer surface area
    3. 20-50% reduction in sentinel ulcer surface area
    4. 0-20% reduction in sentinel ulcer surface area
    5. Any increase in sentinel ulcer surface area
    6. Development of new ulcers
    7. Amputation due to an ulcer
    8. All-cause death

  5. Bates-Jensen Wound Assessment Tool - from Baseline to Week 4 [ Time Frame: 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

  6. Bates-Jensen Wound Assessment Tool - from Baseline to Week 12 [ Time Frame: 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

  7. Bates-Jensen Wound Assessment Tool - from Baseline to Week 26 [ Time Frame: 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

  8. Sentinel ulcer surface area - from Baseline, assessed at Week 4 [ Time Frame: Week 4 ]
    To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 4

  9. Sentinel ulcer surface area - from Baseline, assessed at Week 12 [ Time Frame: Week 12 ]
    To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 12

  10. Sentinel ulcer surface area - from Baseline, assessed at Week 26 [ Time Frame: Week 26 ]
    To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 26

  11. All ulcers total surface area - from Baseline, assessed at Week 4 [ Time Frame: 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

  12. All ulcers total surface area - from Baseline, assessed at Week 12 [ Time Frame: 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

  13. All ulcers total surface area - from Baseline, assessed at Week 26 [ Time Frame: 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

  14. Change over time of self-reported pain [ Time Frame: Week 26 ]
    To determine whether addition of the intervention changes self-reported pain over time, assessed using the 0-to-10 Numerical Rating Scale

  15. Self-reported pain at week 12 [ Time Frame: 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

  16. Change over time of analgesic use [ Time Frame: Week 26 ]
    To determine whether addition of the intervention changes analgesic use over time, as measured by cumulative weighted analgesia dose from baseline to week 26

  17. Analgesic use week 12 [ Time Frame: 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

  18. Composite self-reported pain and analgesic use over time [ Time Frame: Week 26 ]
    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

  19. Composite self-reported pain and analgesic use at week 12 [ Time Frame: 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

  20. Change in self-reported quality of life from Baseline to Week 4 [ Time Frame: 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

  21. Change in self-reported quality of life from Baseline to Week 12 [ Time Frame: 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

  22. Change in self-reported quality of life from Baseline to Week 26 [ Time Frame: 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

  23. Time to first calciphylaxis-attributable infection from Baseline to Week 26 [ Time Frame: Week 26 ]
    Time in days to first calciphylaxis-attributable infection within 26 weeks post-randomisation

  24. All-cause hospitalisation days [ Time Frame: Weeks 0-26 ]
    Count of all cause hospitalisation days (excluding day admissions for dialysis treatment within 26 weeks post-randomisation

  25. Mortality [ Time Frame: Up to 5 years ]
    Incidence of mortality, as derived from hospital reports, within 5-years post-randomisation

  26. Kidney Transplantation [ Time Frame: Up to 5 years ]
    Incidence of kidney transplantation, as derived from hospital reports, within 5-years post-randomisation

  27. Calciphylaxis recurrence [ Time Frame: Up to 5 years ]
    Incidence of calciphylaxis recurrence as derived from hospital reports, within 5-years post-randomisation


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05018221


Contacts
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Contact: Sibyl Masterman 8036 5272 sibyl.masterman@sydney.edu.au
Contact: Meg Jardine 9562 5000 meg.jardine@sydney.edu.au

Locations
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Australia, New South Wales
Concord Repatriation General Hospital Recruiting
Concord, New South Wales, Australia
Contact: Angus Ritchie         
St George Hospital Recruiting
Kogarah, New South Wales, Australia
Contact: Brendan Smyth         
Australia, Queensland
Sunshine Coast Hospital and Health Service Recruiting
Birtinya, Queensland, Australia
Contact: Rathika Krishnasamy         
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia
Contact: Carmel Hawley         
Bundaberg Base Hospital Recruiting
Bundaberg, Queensland, Australia
Contact: Clyson Mutatiri         
Australia, Victoria
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Irene Ruderman         
Sunshine Hospital (Western Health) Recruiting
St Albans, Victoria, Australia
Contact: Eugenia Pedagogos         
Australia
Royal Adelaide Hospital Recruiting
Adelaide, Australia
Contact: Michael Collins         
Monash Medical Centre Recruiting
Clayton, Australia
Contact: Peter Kerr         
New Zealand
Dunedin Hospital Recruiting
Dunedin, New Zealand
Contact: Rob Walker         
Auckland City Hospital (Auckland DHB) Recruiting
Grafton, New Zealand
Contact: Tze Goh         
North Shore Hospital (Waitemata DHB) Recruiting
Takapuna, New Zealand
Contact: Janak de Zoysa         
Tauranga Hospital Recruiting
Tauranga, New Zealand
Contact: Gavin McHaffie         
Sponsors and Collaborators
University of Sydney
Australasian Kidney Trials Network
Northern Care Alliance NHS Foundation Trust
Waitemata District Health Board
Investigators
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Study Chair: Meg Jardine University of Sydney
More Information
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Responsible Party: University of Sydney
ClinicalTrials.gov Identifier: NCT05018221    
Other Study ID Numbers: BEAT-Calci
First Posted: August 24, 2021    Key Record Dates
Last Update Posted: December 5, 2023
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: To be confirmed
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.

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