Calciphylaxis
Conditions
Keywords
calciphylaxis, calcific uremic arteriolopathy, calcinosis, calcium metabolism disorders, metabolic diseases, sodium thiosulfate
Brief summary
This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Thiosulfate Injection for treatment of acute calciphylaxis-associated pain in chronic hemodialysis patients.
Detailed description
This Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Thiosulfate Injection for treatment of acute calciphylaxis-associated pain in chronic hemodialysis patients. Acute calciphylaxis- associated pain intensity will be the primary outcome measure.
Interventions
DRUGSodium Thiosulfate
Intravenous Sodium Thiosulfate Injection (25 grams sodium thiosulfate) to be administered each hemodialysis session (3 times weekly) for 3 weeks
Placebo: to be administered each hemodialysis session (3 times weekly) for 3 weeks
Sponsors
Hope Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed of the investigational nature of the study and sign written informed consent * Willing and able to adhere to all study-related procedures, including adherence to study medication regimen * Male or female ≥18 years old * End-stage renal disease on chronic hemodialysis * Calciphylaxis with active skin lesion(s) of any morphological appearance (including but not limited to livedo, induration, ulceration, etc.) and tissue histology review consistent with calciphylaxis diagnosis. Histological features consistent with calciphylaxis will include soft tissue calcification, microthrombosis, and/or fibrointimal hyperplasia of dermal arterioles * Acute pain associated with calciphylaxis lesions pain intensity score of ≥ 5 at initial screening on the modified BPI/SF scale * Women of childbearing potential must have a pregnancy test (urine or serum \[if anuric\]) at screening and not be pregnant and willing to use an acceptable method of contraception for the entire duration of the study (3 weeks)
Exclusion criteria
* Peritoneal dialysis patients * Current congestive heart failure exacerbation * Baseline abnormalities related to QT prolongation (corrected QT interval \> 470 ms), hypocalcemia (serum albumin-corrected calcium \< 8 mg/dL ), metabolic acidosis (serum bicarbonate \< 18 mmol/L, hypotension (resting systolic blood pressure while seated \< 80), or interdialytic weight gain ≥ 4.0 kg * History of ventricular arrhythmias including ventricular fibrillation or ventricular tachycardia associated with shortness of breath, dizziness, hypotension, or syncope * Any prior (within the past 30 days) or current intravenous Sodium Thiosulfate Injection treatment * Other investigational agent (drug, biologic, or device) study within the past 30 days and/or for the duration of the trial * Pregnant or lactating women * History of allergy to sulfites, thiosulfate, or any component in Sodium Thiosulfate Injection (sulfa allergy is not an exclusion criterion) * Significant other acute or chronic concomitant diseases (including but not limited to hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 3 months * Other serious concurrent or recent medical or psychiatric condition which, in the opinion of the Investigator, makes the patient unsuitable for participation in this study * Ongoing application of dialysate admixed with iron salt e.g. ferric pyrophosphate during the entire trial period (patients who are on dialysate admixed with iron salt at screening are eligible if dialysate admixed with iron salt can be substituted with non-iron based dialysate and patients can be maintained on non-iron based dialysate therapy for the entire duration of trial period) * Recent (within 1 week) history of surgical parathyroidectomy or scheduled for surgical parathyroidectomy during the course of the study * History of opioid addiction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with 30% improvement in pain severity | randomization to 3 weeks | To compare the effects of treatment with intravenous Sodium Thiosulfate Injection vs. placebo for the proportion of patients (responders) who achieve a ≥ 30% reduction based upon pain intensity score (modified BPI/SF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions. | randomization to 3 weeks | Proportion of patients who achieve improvement or stabilization (i.e., not worsening) of skin lesions. |
| Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation. | during week 3 | Occurence of surgical debridement of skin lesions and/or amputation. |
| Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation. | randomization to 3 weeks | Occurrence of surgical debridement of skin lesions and/or amputation. |
| Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity | randomization to 3 weeks | Time in days when a patient achieves a ≥ 30% improvement based upon pain intensity score (modified BPI/SF). |
Countries
Canada, United Kingdom, United States
Outcome results
None listed