Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS (STOPECU)

December 5, 2019 updated by: Nantes University Hospital

Multicentric, Prospective Open-label Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With Atypical Hemolytic Uremic Syndrome (aHUS)

Atypical hemolytic syndrome (aHUS) is a severe renal disease affecting children and adults. It is characterized by the occlusion of intrarenal vessels due to the presence of platelet/fibrin thrombi, and leads to end-stage renal disease in up to 2/3 of patients. The discovery of complement alternative pathway as a major risk factor for aHUS has led to the design of a disease-specific treatment, the anti-C5 monoclonal antibody, eculizumab. Complement inhibition using eculizumab has clearly improved the renal outcome of aHUS patients with a dramatic decrease in the risk of end-stage renal disease. However, the optimal duration of eculizumab therapy is still debated. The present study aims to assess the feasibility and safety of the discontinuation of eculizumab treatment in children and adults with aHUS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A visit (physical examination; blood pressure measurement) will be performed every month for 3 months, and every 3 months for 21 months.

Blood (serum creatinine, platelet count, hemoglobin, LDH, haptoglobin) and urine (proteinuria/creatininuria ratio and microscopic hematuria) tests will be performed every 2 weeks from inclusion to M6 and subsequently every month starting M7 Urine dipstick (for albuminuria and microscopic hematuria) will be performed by the patients at home at least twice a week.

Markers of complement activation and biomarkers of endothelial cells activation and immune cells activation will be assessed at baseline, M1, M3, M6, M9, M12, M18 and M24.

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France
        • CHU Amiens
      • Bordeaux, France
        • CHU Bordeaux
      • Caen, France
        • CHU Caen
      • Chambéry, France
        • CH Métropole Savoie
      • Dijon, France
        • CH Dijon
      • Le Mans, France
        • CH Le mans
      • Lille, France
        • CHRU Lille
      • Lyon, France
        • CHU Lyon
      • Marseille, France
        • AP-HM
      • Metz, France
        • CH Metz Thionville
      • Montpellier, France
        • CHU Montpellier
      • NIce, France
        • CHU Nice
      • Nantes, France
        • CHU Nantes
      • Paris, France
        • Hôpital Européen Georges Pompidou
      • Paris, France
        • Hopital Necker
      • Paris, France
        • Hôpital Tenon
      • Paris, France
        • BICHAT
      • Rouen, France
        • CHU Rouen
      • Sallanches, France
        • CH Alpes Leman
      • Strasbourg, France
        • CHU Strasbourg
      • Suresnes, France
        • Hopital Foch
      • Toulouse, France
        • CHU Toulouse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Children and adults under eculizumab treatment for aHUS (initial episode or relapse) defined by at least two of the following: thrombocytopenia (platelet count < 150 G/L), mechanical hemolytical anaemia (Hb < 10 g:dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schizocytes on blood smear), acute kidney injury (serum creatinine and/or proteinuria/creatininuria > upper limit of normal for age or an increase > 15% compared to baseline levels )
  2. Patients not requiring dialysis.
  3. Adults: HUS remission and normal or stabilized renal function under eculizumab treatment since at least 6 months (3 months in patients with MCP mutations)
  4. Children: age > 3 years at eculizumab withdrawal; HUS remission and normal renal function under eculizumab treatment since at least 3 months in children with isolated MCP mutation, at least 6 months in children with complement mutation other than MCP.

Exclusion Criteria:

  1. Patients on dialysis.
  2. Women treated with eculizumab starting or planning a pregnancy. Pregnancy including the post-partum period is high-risk periods for the occurrence of aHUS.
  3. Patients who did not give informed consent.
  4. Patients under protection of a judicial authority

Patients can be enrolled in the study within ten weeks after Eculizumab stop.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: without eculizumab
Drug: eculizumab
eculizumab discontinuation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation
Time Frame: 24 months

aHUS relapse will be defined by the coexistence of at least two of the following:

  • thrombocytopenia (platelet count < 150 G/L),
  • mechanical hemolytical anaemia (Hb < 10 g/dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schizocytes on blood smear),
  • acute kidney injury (serum creatinine and/or proteinuria/creatininuria > upper limit of normal for age or an increase > 15% compared to baseline levels ),
  • features of thrombotic microangiopathy (glomerular and/or arteriolar thrombi, doubles contours, endothelial cells detachment) in a kidney biopsy, if performed.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Study Director: Fadi FAKHOURI, Pr, Nantes CHU

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2015

Primary Completion (ACTUAL)

December 3, 2019

Study Completion (ACTUAL)

December 3, 2019

Study Registration Dates

First Submitted

October 5, 2015

First Submitted That Met QC Criteria

October 9, 2015

First Posted (ESTIMATE)

October 12, 2015

Study Record Updates

Last Update Posted (ACTUAL)

December 6, 2019

Last Update Submitted That Met QC Criteria

December 5, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC15_0061

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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