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

Primary Purpose

Atypical Hemolytic Uremic Syndrome

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
eculizumab
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atypical Hemolytic Uremic Syndrome focused on measuring atypical hemolytic uremic syndrome (aHUS), eculizumab discontinuation

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU Amiens
  • CHU Bordeaux
  • CHU Caen
  • CH métropole Savoie
  • CH Dijon
  • Ch Le Mans
  • CHRU Lille
  • CHU lyon
  • AP-HM
  • CH Metz Thionville
  • CHU Montpellier
  • CHU Nantes
  • CHU Nice
  • BICHAT
  • Hopital Necker
  • Hopital Tenon
  • Hôpital Européen Georges Pompidou
  • CHU Rouen
  • CH Alpes Léman
  • CHU Strasbourg
  • Hopital FOCH
  • CHU toulouse

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

without eculizumab

Arm Description

Outcomes

Primary Outcome Measures

The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation
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.

Secondary Outcome Measures

Full Information

First Posted
October 5, 2015
Last Updated
December 5, 2019
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02574403
Brief Title
Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
Acronym
STOPECU
Official Title
Multicentric, Prospective Open-label Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With Atypical Hemolytic Uremic Syndrome (aHUS)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
December 3, 2019 (Actual)
Study Completion Date
December 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atypical Hemolytic Uremic Syndrome
Keywords
atypical hemolytic uremic syndrome (aHUS), eculizumab discontinuation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
without eculizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
eculizumab
Intervention Description
eculizumab discontinuation
Primary Outcome Measure Information:
Title
The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation
Description
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.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 ) Patients not requiring dialysis. Adults: HUS remission and normal or stabilized renal function under eculizumab treatment since at least 6 months (3 months in patients with MCP mutations) 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: Patients on dialysis. Women treated with eculizumab starting or planning a pregnancy. Pregnancy including the post-partum period is high-risk periods for the occurrence of aHUS. Patients who did not give informed consent. Patients under protection of a judicial authority Patients can be enrolled in the study within ten weeks after Eculizumab stop.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fadi FAKHOURI, Pr
Organizational Affiliation
Nantes CHU
Official's Role
Study Director
Facility Information:
Facility Name
CHU Amiens
City
Amiens
Country
France
Facility Name
CHU Bordeaux
City
Bordeaux
Country
France
Facility Name
CHU Caen
City
Caen
Country
France
Facility Name
CH métropole Savoie
City
Chambéry
Country
France
Facility Name
CH Dijon
City
Dijon
Country
France
Facility Name
Ch Le Mans
City
Le Mans
Country
France
Facility Name
CHRU Lille
City
Lille
Country
France
Facility Name
CHU lyon
City
Lyon
Country
France
Facility Name
AP-HM
City
Marseille
Country
France
Facility Name
CH Metz Thionville
City
Metz
Country
France
Facility Name
CHU Montpellier
City
Montpellier
Country
France
Facility Name
CHU Nantes
City
Nantes
Country
France
Facility Name
CHU Nice
City
NIce
Country
France
Facility Name
BICHAT
City
Paris
Country
France
Facility Name
Hopital Necker
City
Paris
Country
France
Facility Name
Hopital Tenon
City
Paris
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
Country
France
Facility Name
CHU Rouen
City
Rouen
Country
France
Facility Name
CH Alpes Léman
City
Sallanches
Country
France
Facility Name
CHU Strasbourg
City
Strasbourg
Country
France
Facility Name
Hopital FOCH
City
Suresnes
Country
France
Facility Name
CHU toulouse
City
Toulouse
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
33270832
Citation
Fakhouri F, Fila M, Hummel A, Ribes D, Sellier-Leclerc AL, Ville S, Pouteil-Noble C, Coindre JP, Le Quintrec M, Rondeau E, Boyer O, Provot F, Djeddi D, Hanf W, Delmas Y, Louillet F, Lahoche A, Favre G, Chatelet V, Launay EA, Presne C, Zaloszyc A, Caillard S, Bally S, Raimbourg Q, Tricot L, Mousson C, Le Thuaut A, Loirat C, Fremeaux-Bacchi V. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood. 2021 May 6;137(18):2438-2449. doi: 10.1182/blood.2020009280.
Results Reference
derived

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

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