Efficacy of Lanthanum Carbonate in Calciphylaxis

Calciphylaxis Clinical Trial

Official title:

Evaluation of Efficacy of Lanthanum Carbonate (Fosrenol) in Patients With Calciphylaxis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01289626
• Other study ID #: H-2010-0127
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2011
• Last updated: May 19, 2014
• Start date: February 2011
• Est. completion date: May 2013

Study information

• Verified date: May 2014
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The research question and primary aim is to determine if lanthanum carbonate is effective in treating calciphylaxis by measurement of complete or partial remission of skin lesions. Secondary endpoints will be measured to determine if lanthanum carbonate can lower calcium-phosphorus product levels, intact PTH and mortality. Albumin levels will be measured as a marker of nutritional status and inflammation.

Description:

Calciphylaxis or calcific uremic arteriolopathy is an infrequently occurring although debilitating vasculopathy seen primarily in patients with end stage renal disease (ESRD) which almost always affects the skin. It has a prevalence rate ~4 % in long term hemodialysis patients, with 1-year survival of 45% and an 8-fold risk of death as compared to the general dialysis population. (Surgery 1997;122:1083-1089, Kidney Int 2001;60:324-332). Despite being described in the literature for over 100 years, there has been no proven effective therapy. Lanthanum carbonate (FOSRENOL®) is a potent non-aluminum, non-calcium phosphate binder that was approved for use to reduce serum phosphate levels in patients with end stage renal disease. Since the proposed etiologic mechanism of injury and vascular calcification of calciphylaxis is predominantly hyperphosphatemia, elevated serum PTH, and hypercalcemia, FOSRENOL® would be an ideal pharmacologic agent to utilize in this extremely enigmatic disease (Dermatol Clin. 2008 Oct;26(4):557-68). Furthermore, a recent case report demonstrated a significant improvement in laboratory parameters and calciphylaxis skin lesions with the use of FOSRENOL® (WMJ. 2008 Nov;107(7):335-8). The primary hypothesis is that since calciphylaxis represents the ultimate sequelae of metastatic vascular calcification predominantly involving hyperphosphatemia, elevated serum PTH, and hypercalcemia, FOSRENOL® will be efficacious in its treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• i Participants will have signed a witnessed informed consent. ii Participants will be greater than or equal to 18 years of age iii Chronic renal failure receiving hemodialysis or peritoneal dialysis iv A diagnosis of calciphylaxis proven by skin biopsy or initial dermatology visit within the previous 5 year v Serum phosphorus > 4.5 mg/dL

Exclusion Criteria:

• i Participants are not able to understand or provide written informed consent ii The research team deems that the participant may not be able to follow the study protocol.

iii Non-dependent HD patients receiving dialysis while in acute kidney injury; iv Pregnant dialysis patient v Active gastrointestinal obstruction or bleed vi Active inflammatory bowel disease vii Acute arteriovenous graft occlusion viii Known hypersensitivity to FOSRENOL®

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Calciphylaxis

Intervention

Drug:
• lanthanum carbonate
FOSRENOL® will be administered orally in a dose of 1500- 3750 mg daily in divided doses with meals. Dose escalation will be utilized to a target dose of 3750 mg daily or as designated by clinician over a 4-week period from start of study. The drug will be administered for 12 weeks.
• Lanthanum for calciphylaxis
Lanthanum use in calciphylaxis

Locations

Country	Name	City	State
United States	University of Wisconsin Hospitals	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission of calciphylaxis skin lesions	The primary aim of this study will be the complete or partial remission of calciphylaxis skin lesions after 12 weeks of therapy as defined by the clinician.	12 weeks	No
Secondary	Measurement of phosphorus	Improvement in phosphorous control (target concentrations of 3.5 - 5.5 mg/dL) will also be monitored to correlate the relationship between phosphorous levels and calciphylaxis.	12 weeks	No
Secondary	Intact PTH	Secondary aim will be the control of laboratory parameters of intact PTH	12 weeks	No
Secondary	Albumin	Secondary aim will be the control of laboratory parameters of albumin	12 weeks	No
Secondary	Quality of life	Demonstration of improved DLQI (Dermatology Life Quality Index, http://www.dermatology.org.uk/quality/quality-dlqi-questionnaire.html) scores	12 weeks	No