To evaluate the prevalence of C-TMA in patients presenting with TMA, either with coexisting conditions or not. Furthermore, (i) the diagnostic performance of an in-house developed ex vivo test, (ii) dynamics of complement measures during follow-up,…
ID
Source
Brief title
Condition
- Haemolyses and related conditions
- Nephropathies
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The prevalence of C-TMA in patients presenting with TMA, either with coexisting
conditions or not.
Secondary outcome
The secondary parameters are based on the clinical course of disease, including
hematologic and renal response, refractory TMA, renal recovery, chronic kidney
disease, end-stage kidney disease, and death.
Background summary
Thrombotic microangiopathy (TMA) can occur on the background of complement
dysregulation, i.e., complement-mediated TMA (C-TMA). According to HUS
International*s nomenclature, complement dysregulation should be considered in
patients not presenting with coexisting conditions linked to TMA. Provocative
studies, however, demonstrated that complement dysregulation can be the key
causative factor of poor kidney outcomes in patients presenting with coexisting
conditions, having impact on treatment and prognosis.
Study objective
To evaluate the prevalence of C-TMA in patients presenting with TMA, either
with coexisting conditions or not. Furthermore, (i) the diagnostic performance
of an in-house developed ex vivo test, (ii) dynamics of complement measures
during follow-up, and (iii) clinical, pathologic, and genetic correlates will
be assessed.
Study design
Single-center, prospective, observational cohort study.
Study burden and risks
Patients will be treated and monitored according to routine clinical practice
and therefore, the burden is considered extremely low. The correct recognition
of patients with C-TMA, however, is of utmost importance given the safety and
efficacy of therapeutic complement inhibition in patients with C-TMA. Thus, the
current study may safe kidneys in patients with TMA and, in particular, those
presenting with coexisting conditions.
P. Debyelaan 25
Maastricht 6229HX
NL
P. Debyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Males or females at least 18 years of age;
- Have acute kidney injury, defined as estimated GFR <45 mL/min/1.73m2;
- Have documented TMA either on peripheral blood, defined as Coombs negative
microangiopathic hemolytic anemia (hematocrit <30%, hemoglobin <6.5 mmol/L [<10
g/dL], lactate dehydrogenase >500 U/L, and either schistocytes on peripheral
blood smear or undetectable haptoglobin), and platelets <150,000 per µL, or
kidney biopsy;
- Have primary atypical HUS or a coexisting condition linked to C-TMA:
-- Hypertensive emergency, defined as SBP/DBP of >180/120 mmHg and impending
organ damage secondary to hypertension (at least one of the following:
neurologic disease, hypertensive retinopathy grade III and/or IV, left
ventricular hypertrophy); OR
-- Pregnancy, including 12 weeks postpartum; OR
-- Kidney donor recipient; OR
-- Systemic auto-immune disease associated with TMA, including systemic
sclerosis, systemic lupus erythematosus, anti-phospholipid syndrome;
- Have the ability to understand the requirements of the study, provide written
informed consent, and comply with the study protocol procedures.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Have secondary causes of hypertensive emergency, including renovascular
hypertension, Cushing syndrome, aldosteronism, pheochromocytoma, thyroid
disease;
- Have a nephropathy not related to thrombosis on kidney biopsy;
- Have ADAMTS13 deficiency, defined as ADAMTS13 activity <10%;
- Have a positive stool culture for Shiga toxin producing bacteria;
- Have positive serologic test for viral infections, including HIV and CMV;
- Have a history of malignant disease, excluding non-melanoma skin cancer;
- Have a history of bone marrow or solid organ transplantation;
- Received at least one of the following agents: chemotherapeutics, calcineurin
inhibitors, sirolimus, anti-VEGF agents;
- Have a history of recent past exposure to illicit drug(s).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04745195 |
| CCMO | NL74928.068.20 |