European Calciphylaxis Registry Network

Calciphylaxis Clinical Trial

— EuCalNet  

Official title:

European Calciphylaxis Registry Network

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02635373
• Other study ID #: 13-093
• Status: Recruiting
• Phase: N/A
• First received: November 25, 2015
• Last updated: October 13, 2016
• Start date: December 2015
• Est. completion date: December 2020

Study information

• Verified date: October 2016
• Source: RWTH Aachen University
• Contact: Vincent Brandenburg, MD, Prof.
• Phone: +49 (0)241/80
• Email: calciphylaxis[@]ukaachen.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Observational, registry, prospective, non-interventional collection of CUA patient data. Patient treatment is carried out within clinical routine, at the discretion of the physicians and according to existing treatment guidelines. Participating physicians will not be subject to any instructions with regard to the diagnosis and therapy of their patients.

Description:

Calcific uremic arteriolopathy (CUA, calciphylaxis) is a rare disease (ORPHA280062) with dramatically high mortality characterized clinically by the occurrence of painful debilitating cutaneous lesions and ulcerations. Median survival time is about 1.5 years. Many uncertainties still exist about risk factors and optimal therapy. CUA mainly occurs in patients with severe renal insufficiency or ESRD.

The aim of the present initiative is to establish an international (European) observational registry for CUA patients. This registry will help to reach a critical mass of CUA patients, will allow novel insights into pathophysiology, and will help establishing systematically an overview upon risk factors and long-term outcome of CUA patients. The design of the international registry is supposed to adopt the structure of the presently running nation-wide German calciphylaxis registry.

The investigators plan to initiate a registry in which treating physicians can provide data upon demographics, clinical picture, comorbidities, medical treatments and laboratory data at the time of diagnosis and serial follow-up time points. In addition investigators will build-up a biobank for full blood, serum and plasma samples as well as tissue samples.

The registry will allow investigations regarding potential subgroups of patients (proximal versus distal forms of CUA), geno-phenotype correlations, description of international state-of-the-art treatment, and identification of preventive tools, risk factors and biomarkers for estimation of prognosis.

Furthermore, the registry will be the nidus for further scientific exchange between experts and clinicians on the field of uremic vascular calcification.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosed CUA according to the judgement of locally treating physicians, who have the option to ask for external diagnostic advice from the country-specific sub-investigators

• Male or female aged > 18 years

• Written informed consent prior to study participation

• The subject is not mentally or legally incapacitated

Exclusion Criteria:

• The subject is not able to give informed consent

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Calcific Uremic Arteriolopathy (CUA)
• Calciphylaxis

Locations

Country	Name	City	State
Germany	Department of Medicine, Division of Cardiology, Pulmonary Diseases and Vascular Medicine at the University Hospital, RWTH Aachen	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

References & Publications (14)

Brandenburg VM, Cozzolino M, Ketteler M. Calciphylaxis: a still unmet challenge. J Nephrol. 2011 Mar-Apr;24(2):142-8. Review. — View Citation

Brandenburg VM, Floege J, Ketteler M. Kalzifizierende urämische Arteriolopathie. Der Nephrologe 2009; 4(1):65-66

Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008;45(5):427-36. doi: 10.1159/000124863. Epub 2008 Apr 10. — View Citation

Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. Kidney Int. 2002 Jun;61(6):2210-7. — View Citation

Hafner J, Keusch G, Wahl C, Sauter B, Hürlimann A, von Weizsäcker F, Krayenbühl M, Biedermann K, Brunner U, Helfenstein U. Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad Dermatol. 1995 Dec;33(6):954-62. Review. — View Citation

Jahnen-Dechent W, Schäfer C, Ketteler M, McKee MD. Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification. J Mol Med (Berl). 2008 Apr;86(4):379-89. Epub 2007 Dec 15. Review. — View Citation

Janigan DT, Hirsch DJ, Klassen GA, MacDonald AS. Calcified subcutaneous arterioles with infarcts of the subcutis and skin ("calciphylaxis") in chronic renal failure. Am J Kidney Dis. 2000 Apr;35(4):588-97. Review. — View Citation

Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, Bovi M, Jahnen-Dechent W, Knüchel R, Floege J, Schneider RK. Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant. 2013 Apr;28(4):856-68. doi: 10.1093/ndt/gfs466. Epub 2012 Dec 6. — View Citation

Krueger T, Westenfeld R, Schurgers L, Brandenburg V. Coagulation meets calcification: the vitamin K system. Int J Artif Organs. 2009 Feb;32(2):67-74. Review. — View Citation

Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL, Stehman-Breen CO. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001 Jul;60(1):324-32. — View Citation

Meissner M, Gille J, Kaufmann R. Calciphylaxis: no therapeutic concepts for a poorly understood syndrome? J Dtsch Dermatol Ges. 2006 Dec;4(12):1037-44. Review. English, German. — View Citation

Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003 Aug;112(3):357-66. — View Citation

Weenig RH, Sewell LD, Davis MD, McCarthy JT, Pittelkow MR. Calciphylaxis: natural history, risk factor analysis, and outcome. J Am Acad Dermatol. 2007 Apr;56(4):569-79. Epub 2006 Dec 1. — View Citation

Weenig RH. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor kappa-B. J Am Acad Dermatol. 2008 Mar;58(3):458-71. doi: 10.1016/j.jaad.2007.12.006. Epub 2008 Jan 18. Review. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prognosis of patients with calciphylaxis (survival time)	Survival time is defined as 1) time between diagnosis of calciphylaxis and death (or end of follow-up) or 2) - in case time of diagnosis is not recorded - time between registry recording and death (or end of follow-up). Analysis of survival time is done using the Kaplan-Meier survival analysis and Kaplan-Meier plot. With a Cox hazard model, we will try to identify additional factors influencing survival time. Hereby it is possible to take into consideration interaction between the parameters.	5 years	No
Secondary	Diagnosis of calciphylaxis	An internet based multilingual registry in which treating physicians can provide patients` data (online questionnaire) upon: demographics, the clinical picture including photo documentation and pain scale (VAS) reporting, comorbidities, medical treatments including dialysis and operations, wound management and laboratory data (serum-creatinine, , BUN, ionized / total calcium, serum phosphorus, PTH, alkaline, phosphatase, calcidiol, albumin, CRP, HbA1c, cholesterol, ferritin, hemoglobin, leukocyte count). The international registry will allow a more rapid identification of patients with calciphylaxis than on a national basis alone, will help establish diagnostic algorithms, and will increase the awareness of the disease.	5 years	No
Secondary	Risk factors	More detailed identification of risk factors: the registry will allow investigations regarding potential subgroups of patients (proximal versus distal forms of CUA), geno-phenotype correlations, description of international state-of-the-art treatment, and identification of preventive tools, risk factors and biomarkers for estimation of prognosis.	5 years	No
Secondary	Factors influencing prognosis of patients with calciphylaxis	Evaluation of the collected data from the time point of diagnosis and serial follow-up time points and further scientific exchange between experts and clinicians on the field of uremic vascular calcification will allow identification of subgroups of patients with potentially distinct pattern of risk factors, clinical picture and prognosis, and establishing factors influencing prognosis of patients with calciphylaxis and to develop novel and/or individualized treatment strategies	5 years	No
Secondary	Novel therapeutic options	By increasing the reported cases towards a critical threshold in Europe enabling the performance of RCTs comparing available or upcoming therapeutic options in CUA pts.	5 years	No