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

Purpose

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.

Condition

  • Calciphylaxis

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Sagar Nigwekar, MD
617-726-7872
snigwekar@mgh.harvard.edu

More Details

NCT ID
NCT03150420
Status
Recruiting
Sponsor
Hope Pharmaceuticals

Study Contact

Craig Sherman, MD
480-607-1970
sherman@hopepharm.com

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.