A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients
- Conditions
- Calciphylaxis
- Interventions
- Drug: Placebo-Normal Saline
- Registration Number
- NCT03150420
- Lead Sponsor
- Hope Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 29
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo-Normal Saline Placebo-Normal Saline 0.9% sodium chloride injection, USP (normal saline) Sodium Thiosulfate Sodium Thiosulfate Sodium Thiosulfate Injection (25 grams sodium thiosulfate)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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-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).
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-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.
Trial Locations
- Locations (20)
Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Salford Royal Hospital NHS Foundation Trust
🇬🇧Salford, Manchester, United Kingdom
Sanford Health
🇺🇸Fargo, North Dakota, United States
Veterans Administration Medical Center
🇺🇸Salem, Virginia, United States
Northwestern University Hospital
🇺🇸Chicago, Illinois, United States
The Icahn School of Medicine at Mount Sinai Hospital
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Calgary Foothills Medical Center
🇨🇦Calgary, Alberta, Canada
Churchill Hospital
🇬🇧Oxford, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Centre Hospitalier de l'Universite de Montreal
🇨🇦Montréal, Quebec, Canada
Health Sciences Centre Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Lister Hospital
🇬🇧Stevenage, United Kingdom
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States