Rheopheresis as Adjuvant Treatment of Calciphylaxis

End Stage Renal Disease Clinical Trial

— RHEO-CAL  

Official title:

Efficacy of Rheopheresis as Adjuvant Treatment of Calciphylaxis in Hemodialysis Patients : a Prospective Randomized Controled Single-blind Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04654000
• Other study ID #: 2020_05
• Secondary ID: 2020-A02896-33
• Status: Enrolling by invitation
• Phase: N/A
• Start date: May 2023
• Est. completion date: May 2027

Study information

• Verified date: February 2023
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We propose to set up a prospective randomized controlled trial to control the security and assess the efficacy of adjuvant treatment by rheopheresis in necrotizing-ulcered calciphylaxis in the hemodialysis population.

Description:

Calciphylaxis, also known as uremic calcifying arteriolopathy (UCA), is a rare disease that causes painful ischemic skin lesions due to microvascular calcification and thrombosis of the dermis and subcutaneous adipose tissue. Patients with end-stage renal disease (ESRD) are the main target for calciphylaxis. Rheopheresis is a therapeutic apheresis to treat microcirculatory disorders. This double filtration plasmapheresis eliminates a defined spectrum of high molecular weight proteins from human plasma including relevant factors for vascular inflammation and thrombose. We propose a prospective randomized controlled trial to compared the efficacy of rheopheresis as adjuvant treatment to the standard of care compared to standard care with Sham-apheresis.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 138
• Est. completion date: May 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Calciphylaxis with at least one ulcerated or necrotizing lesion

• End stage renal disease requiring hemodialysis

• Weight superior to 30kg

• Subject affiliated to or beneficiary of a social security system

• Subject having signed written informed consent

A patient with progressing calciphylaxis to ulcerate or necrosis despite conventional treatment may also be included.

Exclusion Criteria:

• KARNOFSKY Performance Status Scale inferior to 30%

• Life expectancy (independently of calciphylaxis) estimated < 6 months according to a referring physician expert in hemodialysis

• Uncontrolled infection (persistence of fever despite appropriate antibiotic therapy)

• Common variable immunodeficiency

• Albumin allergy

• Contra-indication to stop anti-vitamin K treatment

• Severe cognitive or psychiatric disorders, patients unable to give an informed consent or unwilling to participate in the study

• Pregnancy or breastfeeding and all the other categories of people with special protection according to the French Code de la Santé Publique (CSP): patients under legal supervision, patients hospitalized without contentment, patients admitted in social or sanitary structures for care and not research, and patients in emergency situations.

Related Conditions & MeSH terms

• Calciphylaxis
• End Stage Renal Disease
• Kidney Failure, Chronic
• Metabolic Diseases
• Metabolic Disorder
• Rare Diseases

Intervention

Procedure:
• Rheopheresis procedure
rheopheresis is performed using an automated monitor (Plasauto, company HemaT) in a double-filtration cascade. Plasma purify from of high molecular weight proteins
• Sham-apheresis
Sham-apheresis is performed with the same automated monitor (Plasauto, HemaT company). Extracted plasma is not treated through the secondary filter (Rheofilter) and return to the patient.

Locations

Country	Name	City	State
France	Hop Claude Huriez Chu Lille	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with complete wound healing of the calciphylaxis-mediated ischemic lesions after 12 weeks of rheopheresis treatment (a total of 17 sessions).	Complete wound healing is defined as the absence of livedoid peri-lesional inflammation with presence of granulation tissue (stage 3 healing process) and/or epithelization (stage 4) over the entire ulcer surface of calciphylactic lesions. The healing of the lesions will be illustrated with a photographic support. And the pictures will be examined a second time in a centralized and blind way by two referring dermatologists.; In case of multiple calciphylaxis skin lesions, monitoring and evaluation will be done on the largest lesion at the time of patient's inclusion.	at 12 weeks of treatement
Secondary	Percentage of patient with partial wound healing of the calciphylaxis mediated lesions after rheopheresis treatment.	The partial healing is defined by a partial reepithelialization (validated if 3 of following 4 criteria are present: 1-absence of necrosis; 2- granulation; 3 less inflammatory bordering 4- 20% decrease of the lesion size). The evolution of the size of the lesions and the partial healing of the wound will be illustrated by a photographic support.	At 4 weeks and 12 weeks of rheopheresis treatment.
Secondary	Occurrence of new ulcerated calciphylaxis lesions	Occurrence of new ulcerated calciphyalxis lesions frome Baseline to 4 and 12 weeks of treatment.	At 4 weeks and 12 weeks of rheopheresis treatment.
Secondary	Evolution of the self-reporting pain using Numeric Rating Scale (NRS)	The Numeric Rating Scale (NRS) describes the pain intensity at 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme	from baseline (V0) to 12 weeks of rheopheresis (V2)
Secondary	Evolution of the level of antalgic consumed according to World Health Organisation (WHO) classification	The level of consumed antalgic is defined according to the World Health Organization (WHO) classification; Level I analgesics = peripheral analgesics or not morphine have the lowest analgesic power; Level II analgesics = weak morphine.; Level III analgesics = strong morphine agonists and antagonists.	from baseline (V0) to 12 weeks of rheopheresis (V2)
Secondary	Number of days without antibiotics	Number of days the patient receives antibiotics, regardless of the route of administration, whether the patient is treated on an outpatient or inpatient basis.	during the 12 weeks of rheopheresis treatment
Secondary	Quality of life by the Wound quality of life score (Wound-Qol)	The Wound-QoL measures the disease-specific, health-related quality of life of patients with chronic wounds. It consists of 17 items on impairments which are always assessed in retrospect to the preceding seven days.	form baseline (V0) and at 12 weeks
Secondary	Number of days discharged from hospital	Number of days the patient is treated on an outpatient basis.	during the 12 weeks of rheopheresis treatment
Secondary	Overall survival	Survival of patients, whether or not calciphylaxis is cured.	at 12 weeks and 12 months after first rheopheresis.
Secondary	Change in inflammatory proteins	Change in the plasmatic rates of C-reactive protein (CRP) and fibrinogen.	from baseline to 12 weeks-rheopheresis treatment