Clinical trial NCT03150420: A Phase 3 Clinical Trial of Intravenous Sodium Thiosulfate in Acute Calciphylaxis Patients
Official title: A Phase 3, Intravenous Sodium Thiosulfate for Acute Calciphylaxis Treatment: A Multicenter, Randomized, Double-blind, Placebo-controlled, Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Calciphylaxis
Keywords: calciphylaxis
calcific uremic arteriolopathy, calcinosis
calcium metabolism disorders
metabolic diseases
sodium thiosulfate
Lead sponsor: Hope Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-05-12
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with 30% improvement in pain severity
timeFrame: randomization to 3 weeks
Secondary outcomes:
measure: Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions.
timeFrame: randomization to 3 weeks
measure: Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation.
timeFrame: during week 3
measure: Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation.
timeFrame: randomization to 3 weeks
measure: Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity
timeFrame: randomization to 3 weeks
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern University Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Albany
country: United States
facility: Veterans Administration Medical Center
state: New York
city: New York
country: United States
facility: The Icahn School of Medicine at Mount Sinai Hospital
state: New York
city: Fargo
country: United States
facility: Sanford Health
state: North Dakota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Salem
country: United States
facility: Veterans Administration Medical Center
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary Foothills Medical Center
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Salford
country: United Kingdom
facility: Salford Royal Hospital NHS Foundation Trust
state: Manchester
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
Study officials:
affiliation: Hope Pharmaceuticals
name: Craig Sherman, MD
role: STUDY_DIRECTOR
References: