A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients (CALISTA)

A Phase 3, Intravenous Sodium Thiosulfate for Acute Calciphylaxis Treatment: A Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Trial

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.

Study Overview

• Status: Terminated
• Conditions: Calciphylaxis
• Intervention / Treatment: Drug: Sodium Thiosulfate; Drug: Placebo-Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2W 1S7
      • University of Calgary Foothills Medical Center
    • Edmonton, Alberta, Canada, T6G 1Z1
      • University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 3M3
      • Health Sciences Centre Winnipeg
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Université de Montréal
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
  • Stevenage, United Kingdom, SG1 4AB
    • Lister Hospital
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Salford Royal Hospital NHS Foundation Trust
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • Albany, New York, United States, 12208
      • Veterans Administration Medical Center
    • New York, New York, United States, 10029
      • The Icahn School of Medicine at Mount Sinai Hospital
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Rhode Island
    • Providence, Rhode Island, United States, 02914
      • Rhode Island Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Salem, Virginia, United States, 24153
      • Veterans Administration Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Thiosulfate; Sodium Thiosulfate Injection (25 grams sodium thiosulfate)	Drug: Sodium Thiosulfate; Intravenous Sodium Thiosulfate Injection (25 grams sodium thiosulfate) to be administered each hemodialysis session (3 times weekly) for 3 weeks; Other Names: Intravenous Sodium Thiosulfate Injection
Placebo Comparator: Placebo-Normal Saline; 0.9% sodium chloride injection, USP (normal saline)	Drug: Placebo-Normal Saline; Placebo: to be administered each hemodialysis session (3 times weekly) for 3 weeks; Other Names: 0.9% sodium chloride solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with 30% improvement in pain severity	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).	randomization to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions.	Proportion of patients who achieve improvement or stabilization (i.e., not worsening) of skin lesions.	randomization to 3 weeks
Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation.	Occurence of surgical debridement of skin lesions and/or amputation.	during week 3
Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation.	Occurrence of surgical debridement of skin lesions and/or amputation.	randomization to 3 weeks
Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity	Time in days when a patient achieves a ≥ 30% improvement based upon pain intensity score (modified BPI/SF).	randomization to 3 weeks

Collaborators and Investigators

• Sponsor: Hope Pharmaceuticals
• Investigators: Study Director: Craig Sherman, MD, Hope Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): April 15, 2020
• Study Completion (Actual): April 15, 2020

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 15, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: sodium thiosulfate; metabolic diseases; calciphylaxis; calcific uremic arteriolopathy, calcinosis; calcium metabolism disorders
• Additional Relevant MeSH Terms: Metabolic Diseases; Calcium Metabolism Disorders; Calcinosis; Calciphylaxis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Protective Agents; Anti-Bacterial Agents; Antioxidants; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Sodium thiosulfate
• Other Study ID Numbers: ST-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No