Better Evidence and Translation for Calciphylaxis
- Conditions
- Calciphylaxis
- Interventions
- Device: Medium Cut-off DialyserDevice: High Flux DialyserDrug: Placebo capsule (Vitamin K1)Drug: Placebo injection (normal saline)Drug: Placebo tablet (Magnesium citrate)
- Registration Number
- NCT05018221
- Lead Sponsor
- University of Sydney
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
- 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
- Have a new calciphylaxis ulcer present for less than 10 weeks
- Age ≥ 18 years
- Eligible for randomisation in at least one recruiting domain
- The participant and treating physician are willing and able to perform trial procedures
Nil
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Placebo (Double-Blind Period) Placebo capsule (Vitamin K1) Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate Vitamin K1 (Double-Blind Period) Placebo injection (normal saline) Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session. * Placebo Magnesium Citrate * Placebo Sodium Thiosulphate Sodium Thiosulfate (Double-Blind Period) Sodium Thiosulfate 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 Placebo (Double-Blind Period) Placebo injection (normal saline) Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate Medium Cut-off Hemodialysis Medium Cut-off Dialyser Hemodialysis using a medium cut-off dialyser Vitamin K1 (Double-Blind Period) Placebo tablet (Magnesium citrate) Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session. * Placebo Magnesium Citrate * Placebo Sodium Thiosulphate Magnesium Citrate (Double-Blind Period) Placebo capsule (Vitamin K1) 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 Sodium Thiosulfate (Double-Blind Period) Placebo capsule (Vitamin K1) 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 Placebo (Double-Blind Period) Placebo tablet (Magnesium citrate) Placebo Vitamin K1 Placebo Magnesium Citrate Placebo Sodium Thiosulphate Magnesium Citrate (Double-Blind Period) Placebo injection (normal saline) 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 Sodium Thiosulfate (Double-Blind Period) Placebo tablet (Magnesium citrate) 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 High Flux Hemodialysis High Flux Dialyser Hemodialysis using a high flux dialyser Vitamin K1 (Double-Blind Period) Vitamin K1 Dose: 10mg Vitamin K1 capsules, administered 3 times per week following the subject's hemodialysis session. * Placebo Magnesium Citrate * Placebo Sodium Thiosulphate Magnesium Citrate (Double-Blind Period) Magnesium citrate 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
- Primary Outcome Measures
Name Time Method BEAT-Calci Wound Assessment Scale (BCWAS) - Baseline to Week 12 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
Name Time Method Distribution of each of the individual components of the BCWAS, assessed at Week 12 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 deathChange over time of self-reported pain Week 26 To determine whether addition of the intervention changes self-reported pain over time, assessed using the 0-to-10 Numerical Rating Scale
Sentinel ulcer surface area - from Baseline, assessed at Week 4 Week 4 To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 4
Sentinel ulcer surface area - from Baseline, assessed at Week 26 Week 26 To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 26
All ulcers total surface area - from Baseline, assessed at Week 4 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
Bates-Jensen Wound Assessment Tool - from Baseline to Week 26 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
Distribution of each of the individual components of the BCWAS, assessed at Weeks 4 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 deathDistribution of each of the individual components of the BCWAS, assessed at Week 26 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 deathBates-Jensen Wound Assessment Tool - from Baseline to Week 4 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
Self-reported pain at week 12 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
BEAT-Calci Wound Assessment Scale - Baseline to Week 26 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 deathBates-Jensen Wound Assessment Tool - from Baseline to Week 12 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
Sentinel ulcer surface area - from Baseline, assessed at Week 12 Week 12 To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 12
All ulcers total surface area - from Baseline, assessed at Week 26 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
Composite self-reported pain and analgesic use at week 12 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
Change in self-reported quality of life from Baseline to Week 4 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
Change in self-reported quality of life from Baseline to Week 12 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
Change in self-reported quality of life from Baseline to Week 26 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
All ulcers total surface area - from Baseline, assessed at Week 12 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
Change over time of analgesic use 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
Analgesic use week 12 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 to first calciphylaxis-attributable infection from Baseline to Week 26 Week 26 Time in days to first calciphylaxis-attributable infection within 26 weeks post-randomisation
Mortality Up to 5 years Incidence of mortality, as derived from hospital reports, within 5-years post-randomisation
Kidney Transplantation Up to 5 years Incidence of kidney transplantation, as derived from hospital reports, within 5-years post-randomisation
Calciphylaxis recurrence Up to 5 years Incidence of calciphylaxis recurrence as derived from hospital reports, within 5-years post-randomisation
Composite self-reported pain and analgesic use over time 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
All-cause hospitalisation days Weeks 0-26 Count of all cause hospitalisation days (excluding day admissions for dialysis treatment within 26 weeks post-randomisation
Trial Locations
- Locations (14)
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Sunshine Hospital (Western Health)
🇦🇺St Albans, Victoria, Australia
Tauranga Hospital
🇳🇿Tauranga, New Zealand
Bundaberg Base Hospital
🇦🇺Bundaberg, Queensland, Australia
Sunshine Coast Hospital and Health Service
🇦🇺Birtinya, Queensland, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Monash Medical Centre
🇦🇺Clayton, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Dunedin Hospital
🇳🇿Dunedin, New Zealand
Auckland City Hospital (Auckland DHB)
🇳🇿Grafton, New Zealand
North Shore Hospital (Waitemata DHB)
🇳🇿Takapuna, New Zealand
Whangarei Hospital
🇳🇿Whangarei, New Zealand
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia