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

Calciphylaxis Clinical Trial

— CALISTA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03150420
• Other study ID #: ST-001
• Status: Terminated
• Phase: Phase 3
• Start date: May 24, 2017
• Est. completion date: April 15, 2020

Study information

• Verified date: May 2020
• Source: Hope Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: April 15, 2020
• Est. primary completion date: April 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Calciphylaxis

Intervention

Drug:
• Sodium Thiosulfate
Intravenous Sodium Thiosulfate Injection (25 grams sodium thiosulfate) to be administered each hemodialysis session (3 times weekly) for 3 weeks
• Placebo-Normal Saline
Placebo: to be administered each hemodialysis session (3 times weekly) for 3 weeks

Locations

Country	Name	City	State
Canada	University of Calgary Foothills Medical Center	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Health Sciences Centre Winnipeg	Winnipeg	Manitoba
United Kingdom	Hammersmith Hospital	London
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Salford Royal Hospital NHS Foundation Trust	Salford	Manchester
United Kingdom	Lister Hospital	Stevenage
United States	Veterans Administration Medical Center	Albany	New York
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University Hospital	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Sanford Health	Fargo	North Dakota
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic	Jacksonville	Florida
United States	Loyola University Medical Center	Maywood	Illinois
United States	The Icahn School of Medicine at Mount Sinai Hospital	New York	New York
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Veterans Administration Medical Center	Salem	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Hope Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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	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	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