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

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ClinicalTrials.gov Identifier: NCT02574403
Recruitment Status : Active, not recruiting
First Posted : October 12, 2015
Last Update Posted : November 24, 2017
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

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.

Condition or disease Intervention/treatment Phase
Atypical Hemolytic Uremic Syndrome Drug: eculizumab Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2015
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019


Arm Intervention/treatment
Experimental: without eculizumab Drug: eculizumab
eculizumab discontinuation




Primary Outcome Measures :
  1. The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation [ Time Frame: 24 months ]

    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.



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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02574403


Locations
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
Hopital Necker
Paris, France
Hopital Tenon
Paris, France
Hôpital Européen Georges Pompidou
Paris, France
CHU Rouen
Rouen, France
CH Alpes Léman
Sallanches, France
CHU Strasbourg
Strasbourg, France
Hopital FOCH
Suresnes, France
CHU toulouse
Toulouse, France
Sponsors and Collaborators
Nantes University Hospital
Investigators
Study Director: Fadi FAKHOURI, Pr Nantes CHU

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02574403     History of Changes
Other Study ID Numbers: RC15_0061
First Posted: October 12, 2015    Key Record Dates
Last Update Posted: November 24, 2017
Last Verified: November 2017

Keywords provided by Nantes University Hospital:
atypical hemolytic uremic syndrome (aHUS)
eculizumab discontinuation

Additional relevant MeSH terms:
Syndrome
Hemolysis
Azotemia
Hemolytic-Uremic Syndrome
Atypical Hemolytic Uremic Syndrome
Disease
Pathologic Processes
Uremia
Kidney Diseases
Urologic Diseases
Anemia, Hemolytic
Anemia
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders