NCT02574403

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Nov 2015

Longer than P75 for phase_4

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 5, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 12, 2015

Completed
20 days until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 3, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 3, 2019

Completed
Last Updated

December 6, 2019

Status Verified

December 1, 2019

Enrollment Period

4.1 years

First QC Date

October 5, 2015

Last Update Submit

December 5, 2019

Conditions

Keywords

atypical hemolytic uremic syndrome (aHUS)eculizumab discontinuation

Outcome Measures

Primary Outcomes (1)

  • 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.

    24 months

Study Arms (1)

without eculizumab

EXPERIMENTAL
Drug: eculizumab

Interventions

eculizumab discontinuation

without eculizumab

Eligibility Criteria

Age3 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

CHU Amiens

Amiens, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU Caen

Caen, France

Location

CH métropole Savoie

Chambéry, France

Location

CH Dijon

Dijon, France

Location

Ch Le Mans

Le Mans, France

Location

CHRU Lille

Lille, France

Location

CHU lyon

Lyon, France

Location

AP-HM

Marseille, France

Location

CH Metz Thionville

Metz, France

Location

CHU Montpellier

Montpellier, France

Location

CHU Nantes

Nantes, France

Location

CHU Nice

Nice, France

Location

BICHAT

Paris, France

Location

Hopital Necker

Paris, France

Location

Hopital Tenon

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

CHU Rouen

Rouen, France

Location

CH Alpes Léman

Sallanches, France

Location

CHU Strasbourg

Strasbourg, France

Location

Hopital FOCH

Suresnes, France

Location

CHU toulouse

Toulouse, France

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Hemolytic-Uremic SyndromeUremiaKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesThrombotic MicroangiopathiesThrombocytopeniaBlood Platelet DisordersCytopenia

Study Officials

  • Fadi FAKHOURI, Pr

    Nantes CHU

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 5, 2015

First Posted

October 12, 2015

Study Start

November 1, 2015

Primary Completion

December 3, 2019

Study Completion

December 3, 2019

Last Updated

December 6, 2019

Record last verified: 2019-12

Locations