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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02574403
Other study ID # RC15_0061
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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