Better Evidence and Translation for Calciphylaxis

Calciphylaxis Clinical Trial

— BEAT-Calci  

Official title:

Better Evidence and Translation for Calciphylaxis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05018221
• Other study ID #: BEAT-Calci
• Status: Recruiting
• Phase: Phase 3
• Start date: August 26, 2021
• Est. completion date: December 2029

Study information

• Verified date: December 2023
• Source: University of Sydney
• Contact: Sibyl Masterman
• Phone: 8036 5272
• Email: sibyl.masterman[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: December 2029
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Calciphylaxis

Intervention

Drug:
• Vitamin K1
Vitamin K1 capsule (10mg) to be administered 3 times per week following the subject's hemodialysis session.
• 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.
• Sodium Thiosulfate
Sodium Thiosulfate injection (25g/100ml) to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.

Device:
• High Flux Dialyser
Hemodialysis using a high flux dialyser.
• Medium Cut-off Dialyser
Hemodialysis using a medium cut-off dialyser.

Drug:
• Placebo injection (normal saline)
Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
• Placebo capsule (Vitamin K1)
Placebo to be administered 3 times per week following the subject's hemodialysis session.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Sunshine Coast Hospital and Health Service	Birtinya	Queensland
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Bundaberg Base Hospital	Bundaberg	Queensland
Australia	Monash Medical Centre	Clayton
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	Sunshine Hospital (Western Health)	St Albans	Victoria
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Auckland City Hospital (Auckland DHB)	Grafton
New Zealand	North Shore Hospital (Waitemata DHB)	Takapuna
New Zealand	Tauranga Hospital	Tauranga

Sponsors (4)

Lead Sponsor	Collaborator
University of Sydney	Australasian Kidney Trials Network, Northern Care Alliance NHS Foundation Trust, Waitemata District Health Board

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	All-cause hospitalisation days	Count of all cause hospitalisation days (excluding day admissions for dialysis treatment within 26 weeks post-randomisation	Weeks 0-26
Secondary	Mortality	Incidence of mortality, as derived from hospital reports, within 5-years post-randomisation	Up to 5 years
Secondary	Kidney Transplantation	Incidence of kidney transplantation, as derived from hospital reports, within 5-years post-randomisation	Up to 5 years
Secondary	Calciphylaxis recurrence	Incidence of calciphylaxis recurrence as derived from hospital reports, within 5-years post-randomisation	Up to 5 years