Therapeutic Orientation Test in Thrombotic Microangiopathy (TOTEM)

Haemolytic and Uraemic Syndrome (HUS) is a serious disease requiring rapid diagnosis and management. The atypical HUS diagnosis has been greatly improved by anti-CS antibody (Eculizumab) wich block alternative complement pathway activation. To rise treatment success, Eculizumab introduction should be as early as possible. In some secondary HUS (infection, drugs…) complement is also involved as "second-hit".

To date, there is no tool to confirm complement involvement in a HUS at diagnosis stage. This study suggest to evaluate a therapeutic orientation test, in order to determine the complement implication in HUS diagnosis. The test evaluates the complement deposits on endothelial cell surface in vitro, compared to a normal human serum.

In order to determine the test performance, first the positive or negative results will be compared to the HUS clinical evolution, treated or not by the clinician with Eculizumab. Second, the test results will be compared to the presence of alternative complement pathway regulation abnormalities.

Study Overview

• Status: Completed
• Conditions: Thrombotic Micro-angiopathy
• Intervention / Treatment: Diagnostic test: Therapeutic orientation test for TMA

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • CHU de Bordeaux
  • Cabestany, France
    • Site Médipôle Cabestany
  • Castelnau-le-Lez, France
    • Centre Nephrocare Castelnau-le-Lez
  • Grenoble, France
    • CHU de Grenoble
  • Lille, France
    • CHU de Lille
  • Limoges, France
    • CHU de Limoges
  • Marseille, France
    • APHM-Hôpital de la Conception
  • Montpellier, France
    • Montpellier University Hospital
  • Nantes, France
    • CHU de Nantes
  • Narbonne, France
    • HPGN- Narbonne
  • Nice, France
    • CHU de Nice
  • Nîmes, France
    • CHU de Nîmes
  • Paris, France
    • APHP-Hôpital Tenon
  • Paris, France
    • Hôpital Paris Necker
  • Perpignan, France
    • CH de Perpignan
  • Poitiers, France
    • CHU de Poitiers
  • Rouen, France
    • CHU de Rouen
  • Strasbourg, France
    • Hopitaux Universitaires de Strasbourg
  • Toulouse, France
    • CHU de Toulouse
  • Tours, France
    • CHRU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

TMA with:

• mechanic haemolytic anemia, undetectable haptoglobin, LDH>1.5*LNS
• thrombopenia
• acute kidney injury TMA on native kidney or in post-transplantation.

Exclusion Criteria:

• DIVC patients
• plasma exchange during 1 month before sample collection
• treatment by Eculizumab before sample collection
• no consent
• not beneficiary of a social security
• pregnancy or breastfeeding
• patient Under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Thrombotic micro-angiopathy	Diagnostic test: Therapeutic orientation test for TMA; Therapeutic orientation test for TMA performed on blood sample at inclusion, first visit at 1 month and last visit at 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic orientation test sensitivity	The proportion of patients testing positive among those receiving a relevant Eculizumab treatment ( TMA resolution with treatment or presence of abnormalities in alternative complement pathway.	Through study completion, an average of 3 years.
Therapeutic orientation test specificity	The proportion of patients testing negative among patients who did not receive Eculizumab treatment.(TMA resolution without treatment or therapeutic failure with Eculizumab).	Through study completion, an average of 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untreated test positive patients	The proportion of patients with positive test but untreated by Eculizumab, and who therefore could have benefited from treatment.	Through study completion, an average of 3 years.

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2021
• Primary Completion (Actual): April 13, 2026
• Study Completion (Actual): April 13, 2026

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Complement; Diagnostic; Nephrology; Thrombotic micro-angiopathy; Haemolytic and Uraemic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease; Hemolysis
• Other Study ID Numbers: RECHMPL19_0075

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No