Calciphylaxis
Conditions
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.
Interventions
DRUGVitamin K1
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.
DRUGSodium Thiosulfate
Sodium Thiosulfate injection (25g/100ml) to be administered intravenously 3 times per week, during the subject's last hour of hemodialysis.
DEVICEHigh Flux Dialyser
Hemodialysis using a high flux dialyser.
DEVICEMedium Cut-off 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.
DRUGPlacebo capsule (Vitamin K1)
Placebo to be administered 3 times per week following the subject's hemodialysis session.
DRUGPlacebo 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.
Sponsors
Australasian Kidney Trials Network
Northern Care Alliance NHS Foundation Trust
Waitemata District Health Board
Vantive Health LLC
Berry Consultants
University of Sydney
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
Intervention model description
Adaptive, platform, randomized controlled trial, involving multiple interventions spanning several domains of therapeutic care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 death |
| 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 death |
| Distribution 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 death |
| Bates-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 |
| Bates-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 |
| 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 |
| 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 12 | Week 12 | To determine whether addition of the intervention changes the surface area of sentinel ulcer from Baseline, assessed at Week 12 |
| 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 |
| 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 |
| 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 |
| Change 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 |
| 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 death |
| 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 |
| 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 |
| 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 |
| 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 |
| All-cause hospitalisation days | Weeks 0-26 | Count of all cause hospitalisation days (excluding day admissions for dialysis treatment 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 |
| 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 |
Countries
Australia, New Zealand
Contacts
Primary ContactSibyl Masterman
Backup ContactMeg Jardine
Outcome results
None listed