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

Atypical Hemolytic Uremic Syndrome Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02574403
• Other study ID #: RC15_0061
• Status: Completed
• Phase: Phase 4
• Start date: November 2015
• Est. completion date: December 3, 2019

Study information

• Verified date: December 2019
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: December 3, 2019
• Est. primary completion date: December 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atypical Hemolytic Uremic Syndrome
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

Drug:
• eculizumab
eculizumab discontinuation

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU Bordeaux	Bordeaux
France	CHU Caen	Caen
France	CH métropole Savoie	Chambéry
France	CH Dijon	Dijon
France	Ch Le Mans	Le Mans
France	CHRU Lille	Lille
France	CHU lyon	Lyon
France	AP-HM	Marseille
France	CH Metz Thionville	Metz
France	CHU Montpellier	Montpellier
France	CHU Nantes	Nantes
France	CHU Nice	NIce
France	BICHAT	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hopital Necker	Paris
France	Hopital Tenon	Paris
France	CHU Rouen	Rouen
France	CH Alpes Léman	Sallanches
France	CHU Strasbourg	Strasbourg
France	Hopital FOCH	Suresnes
France	CHU toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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