Clinical trial NCT02574403: Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atypical Hemolytic Uremic Syndrome
Keywords: atypical hemolytic uremic syndrome (aHUS)
eculizumab discontinuation
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2015-10-12
Enrollment: 58
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHU Caen
city: Chambéry
country: France
facility: CH métropole Savoie
city: Dijon
country: France
facility: CH Dijon
city: Le Mans
country: France
facility: Ch Le Mans
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: CHU lyon
city: Marseille
country: France
facility: AP-HM
city: Metz
country: France
facility: CH Metz Thionville
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: CHU Nantes
city: NIce
country: France
facility: CHU Nice
city: Paris
country: France
facility: BICHAT
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital Tenon
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Rouen
country: France
facility: CHU Rouen
city: Sallanches
country: France
facility: CH Alpes Léman
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Suresnes
country: France
facility: Hopital FOCH
city: Toulouse
country: France
facility: CHU toulouse
Study officials:
affiliation: Nantes CHU
name: Fadi FAKHOURI, Pr
role: STUDY_DIRECTOR
References:
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.