Back to resultsRheopheresis as Adjuvant Treatment of Calciphylaxis (RHEO-CAL)
Primary Purpose
Metabolic Disorder, End Stage Renal Disease, Rare Diseases
Status
Enrolling by invitation
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Rheopheresis procedure
Sham-apheresis
Sponsored by
About this trial
This is an interventional diagnostic trial for Metabolic Disorder focused on measuring Calciphylaxis, Rheopheresis, Hemodialysis, Chronic kidney disease
Eligibility Criteria
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.
Sites / Locations
- Hop Claude Huriez Chu Lille
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Rheopheresis group
Sham-apheresis group
Arm Description
In addition to the standards of care, the experimental group will carry out the rheopheresis in two stages: Stage 1: induction treatment: 3 apheresis sessions during the first week (w0; i.e. between D1 and D7) and then 2 apheresis sessions each week for 3 weeks (from w1 to w3; i.e. between D8 and D28) ; Step 2: maintenance treatment with 1 apheresis session per week until the 11th week (i.e. between D29 and D84).
In addition to the standards of care, the comparator group will carry out Sham-apheresis sessions according to the same scheme as the rheopheresis sessions of the experimental group.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Occurrence of new ulcerated calciphylaxis lesions
Occurrence of new ulcerated calciphyalxis lesions frome Baseline to 4 and 12 weeks of treatment.
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
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.
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.
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.
Number of days discharged from hospital
Number of days the patient is treated on an outpatient basis.
Overall survival
Survival of patients, whether or not calciphylaxis is cured.
Change in inflammatory proteins
Change in the plasmatic rates of C-reactive protein (CRP) and fibrinogen.
Full Information
NCT ID
NCT04654000
First Posted
December 2, 2020
Last Updated
February 14, 2023
Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France
1. Study Identification
Unique Protocol Identification Number
NCT04654000
Brief Title
Rheopheresis as Adjuvant Treatment of Calciphylaxis
Acronym
RHEO-CAL
Official Title
Efficacy of Rheopheresis as Adjuvant Treatment of Calciphylaxis in Hemodialysis Patients : a Prospective Randomized Controled Single-blind Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
April 2027 (Anticipated)
Study Completion Date
May 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Disorder, End Stage Renal Disease, Rare Diseases
Keywords
Calciphylaxis, Rheopheresis, Hemodialysis, Chronic kidney disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
138 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rheopheresis group
Arm Type
Experimental
Arm Description
In addition to the standards of care, the experimental group will carry out the rheopheresis in two stages:
Stage 1: induction treatment: 3 apheresis sessions during the first week (w0; i.e. between D1 and D7) and then 2 apheresis sessions each week for 3 weeks (from w1 to w3; i.e. between D8 and D28) ;
Step 2: maintenance treatment with 1 apheresis session per week until the 11th week (i.e. between D29 and D84).
Arm Title
Sham-apheresis group
Arm Type
Sham Comparator
Arm Description
In addition to the standards of care, the comparator group will carry out Sham-apheresis sessions according to the same scheme as the rheopheresis sessions of the experimental group.
Intervention Type
Procedure
Intervention Name(s)
Rheopheresis procedure
Intervention Description
rheopheresis is performed using an automated monitor (Plasauto, company HemaT) in a double-filtration cascade. Plasma purify from of high molecular weight proteins
Intervention Type
Procedure
Intervention Name(s)
Sham-apheresis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of patients with complete wound healing of the calciphylaxis-mediated ischemic lesions after 12 weeks of rheopheresis treatment (a total of 17 sessions).
Description
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.
Time Frame
at 12 weeks of treatement
Secondary Outcome Measure Information:
Title
Percentage of patient with partial wound healing of the calciphylaxis mediated lesions after rheopheresis treatment.
Description
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.
Time Frame
At 4 weeks and 12 weeks of rheopheresis treatment.
Title
Occurrence of new ulcerated calciphylaxis lesions
Description
Occurrence of new ulcerated calciphyalxis lesions frome Baseline to 4 and 12 weeks of treatment.
Time Frame
At 4 weeks and 12 weeks of rheopheresis treatment.
Title
Evolution of the self-reporting pain using Numeric Rating Scale (NRS)
Description
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
Time Frame
from baseline (V0) to 12 weeks of rheopheresis (V2)
Title
Evolution of the level of antalgic consumed according to World Health Organisation (WHO) classification
Description
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.
Time Frame
from baseline (V0) to 12 weeks of rheopheresis (V2)
Title
Number of days without antibiotics
Description
Number of days the patient receives antibiotics, regardless of the route of administration, whether the patient is treated on an outpatient or inpatient basis.
Time Frame
during the 12 weeks of rheopheresis treatment
Title
Quality of life by the Wound quality of life score (Wound-Qol)
Description
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.
Time Frame
form baseline (V0) and at 12 weeks
Title
Number of days discharged from hospital
Description
Number of days the patient is treated on an outpatient basis.
Time Frame
during the 12 weeks of rheopheresis treatment
Title
Overall survival
Description
Survival of patients, whether or not calciphylaxis is cured.
Time Frame
at 12 weeks and 12 months after first rheopheresis.
Title
Change in inflammatory proteins
Description
Change in the plasmatic rates of C-reactive protein (CRP) and fibrinogen.
Time Frame
from baseline to 12 weeks-rheopheresis treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arnaud Lionet, MD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hop Claude Huriez Chu Lille
City
Lille
Country
France
12. IPD Sharing Statement
Learn more about this trial
Rheopheresis as Adjuvant Treatment of Calciphylaxis
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