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

Hope Pharmaceuticals20 sites in 3 countries29 target enrollmentMay 24, 2017

ConditionsCalciphylaxis

InterventionsSodium Thiosulfate Placebo-Normal Saline

Overview

Phase: Phase 3
Intervention: Sodium Thiosulfate
Conditions: Calciphylaxis
Sponsor: Hope Pharmaceuticals
Enrollment: 29
Locations: 20
Primary Endpoint: Number of patients with 30% improvement in pain severity
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 24, 2017

End Date

April 15, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hope Pharmaceuticals

Responsible Party

Sponsor

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

Arms & Interventions

Sodium Thiosulfate

Sodium Thiosulfate Injection (25 grams sodium thiosulfate)

Intervention: Sodium Thiosulfate

Placebo-Normal Saline

0.9% sodium chloride injection, USP (normal saline)

Intervention: Placebo-Normal Saline

Outcomes

Primary Outcomes

Number of patients with 30% improvement in pain severity

Time Frame: 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 Outcomes

Secondary Endpoint-b: Occurence of surgical debridement of skin lesions and/or amputation.(during week 3)
Secondary Endpoint-d: Time to achieve ≥ 30% improvement in pain severity(randomization to 3 weeks)
Secondary Endpoint-a: Number of patients with stabilization or improvement in calciphylaxis skin lesions.(randomization to 3 weeks)
Secondary Endpoint-c: Occurrence of surgical debridement of skin lesions and/or amputation.(randomization to 3 weeks)