This global platform study will evaluate multiple interventions, across several domains of therapeutic care, in adult patients with kidney failure and newly diagnosed calciphylaxis.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
350
Vitamin K1 capsule (10mg) to be administered 3 times per week following the subject's hemodialysis session.
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 injection (25g/100ml) to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
Concord Repatriation General Hospital
Concord, New South Wales, Australia
RECRUITINGBEAT-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: 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
Time frame: Week 12
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: 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
Time frame: 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: 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
Time frame: Week 4
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Hemodialysis using a high flux dialyser.
Hemodialysis using a medium cut-off dialyser.
Placebo to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
Placebo to be administered 3 times per week following the subject's hemodialysis session.
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.
St George Hospital
Kogarah, New South Wales, Australia
RECRUITINGLiverpool Hospital
Liverpool, New South Wales, Australia
RECRUITINGJohn Hunter Hospital
New Lambton Heights, New South Wales, Australia
RECRUITINGWestmead Hospital
Westmead, New South Wales, Australia
RECRUITINGSunshine Coast Hospital and Health Service
Birtinya, Queensland, Australia
RECRUITINGPrincess Alexandra Hospital
Brisbane, Queensland, Australia
RECRUITINGBundaberg Base Hospital
Bundaberg, Queensland, Australia
RECRUITINGCairns Hospital
Cairns, Queensland, Australia
RECRUITINGTownsville Hospital
Douglas, Queensland, Australia
RECRUITING...and 11 more locations
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: 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
Time frame: 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: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 26
All-cause hospitalisation days
Count of all cause hospitalisation days (excluding day admissions for dialysis treatment within 26 weeks post-randomisation
Time frame: Weeks 0-26
Mortality
Incidence of mortality, as derived from hospital reports, within 5-years post-randomisation
Time frame: Up to 5 years
Kidney Transplantation
Incidence of kidney transplantation, as derived from hospital reports, within 5-years post-randomisation
Time frame: Up to 5 years
Calciphylaxis recurrence
Incidence of calciphylaxis recurrence as derived from hospital reports, within 5-years post-randomisation
Time frame: Up to 5 years