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Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (EspacECU) (EspacECU)

Primary Purpose

Hemolytic-Uremic Syndrome, Atypical

Status
Recruiting
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Spacing of Eculizumab infusions
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemolytic-Uremic Syndrome, Atypical focused on measuring Hemolytic-Uremic Syndrome, Kidney Diseases, Thrombotic Microangiopathies, Therapeutic drug monitoring, Eculizumab tailoring, Cost-utility analysis, Markov model

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adults with an atypical Hemolytic and Uremic Syndrome defined by at least 2 of the following parameters:

    • Thrombopenia (platelet count < 150 G/L)
    • Mechanical lytic anemia (Hb < 10 g/L, Lactate dehydrogenase > upper limit of normal, undetectable haptoglobin, presence of schistocytes on blood smear)
    • Acute renal failure

  2. Eculizumab treatment

    • Without project of withdrawal in the next 18 months
    • Started since at least 6 months
    • Administrated with an unchanged administration schedule since at least 3 months (initial episode or relapse)
  3. Atypical Hemolytic and Uremic Syndrome in remission
  4. Patients who give informed consent.

Exclusion Criteria:

  1. Patients on dialysis.
  2. Women treated starting or planning a pregnancy.
  3. Patients suffering from a typical or secondary microangiopathic hemolytic anemia (drugs, malignancies, autoimmune disease...)
  4. Patients under protection of a judicial authority

Sites / Locations

  • CHU Amiens PicardieRecruiting
  • CHU d'AngersRecruiting
  • Hôpital TenonRecruiting
  • CHU BesançonRecruiting
  • Hôpital de la Côte de NacreRecruiting
  • Hôpital Louis PasteurRecruiting
  • Hôpital Gabriel MontpiedRecruiting
  • Hospices Civils de LyonRecruiting
  • Hopital de la conceptionRecruiting
  • Hôpitaux de BraboisRecruiting
  • Hotel DieuRecruiting
  • Hopital NeckerRecruiting
  • Hopital Pasteur 2Recruiting
  • Hôpital de la MilétrieRecruiting
  • Hôpital Maison BlancheRecruiting
  • Hôpital PontchaillouRecruiting
  • Hôpital de Bois-GuillaumeRecruiting
  • Nouvel Hôpital CivilRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Therapeutic drug monitoring

Control

Arm Description

Tailored dosing schedule for eculizumab based on therapeutic drug monitoring

Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm.

Outcomes

Primary Outcome Measures

Incremental Cost-Utility Ratio (ICUR) at 18 months of a personalized spacing of eculizumab infusions compared to the usual administration scheme without personalization, from the French health insurance perspective.
The ICUR will express the incremental cost per QALY (Quality-adjusted Life Years) gained over a 18-month time horizon. QALYs will be estimated from patient responses to the EQ-5D-5L instrument (EuroQol group - 5 Dimensions - 5 levels). Costs related to hospital care resources (medicalized information system program), transports (patient diary), eculizumab concentration dosing (cost estimation) will be estimated from the French Health Insurance perspective. Cost and QALY estimates will be used to estimate the within-trial ICUR.

Secondary Outcome Measures

Incremental Cost-Utility Ratio at 5 years (incremental cost per QALY gained) of a personalized spacing of the eculizumab infusions compared to the usual administration scheme without personalization, estimated from a Markov model.
A Markov model will represent the patient's clinical progression across different health states over a 5-year period. Markov modelling will use the within-trial data to estimate the transition probabilities, the state cost and utility values.
Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions
The financial impact of spreading the strategy of personalized spacing of eculizumab infusions, in patients in remission with atypical hemolytic uraemic syndrome requiring long-term treatment, will be estimated per year and over a 5-year period, from the French Health Insurance (using a budget impact model).
Quality of life measured over a 18-month period using different specific scales (KDQoL-SF, ReTransQoL-Version 2) dedicated to patients with renal disease
KDQoL-SF (Kidney Disease and Quality of Life™ Short Form) survey is a kidney-disease-specific quality of life instrument that assesses four domains : health, kidney disease, effects of kidney disease on daily life, satisfaction with care. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. RTQ-V2 (ReTransQoL-Version 2) survey is a specific quality of life instrument for renal transplant recipients. It comprises of 32 items describing five domains: Physical Health, Social Functioning, Medical Care, Treatment and Fear of Losing Graft. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. KDQoL-SF survey will be used for all patients, and RTQ-V2 survey for kidney transplant patients only. The quality of life will be measured every three months.
Determining the factors of intra- and inter- individual variability of eculizumab concentrations.
A study will be performed to determine whether biological and genetic (complement genetic variants reported as cause of HUS) parameters influence trough concentrations of eculizumab

Full Information

First Posted
February 2, 2021
Last Updated
February 10, 2022
Sponsor
University Hospital, Tours
Collaborators
Centre Hospitalier Universitaire, Amiens, University Hospital, Angers, Centre Hospitalier Universitaire de Besancon, University Hospital, Caen, Centre Hospitalier of Chartres, Nantes University Hospital, University of Nancy, Poitiers University Hospital, Rennes University Hospital, University Hospital, Rouen, University Hospital, Strasbourg, France, Centre Hospitalier Universitaire de Nice, Hôpital Necker-Enfants Malades, Tenon Hospital, Paris, University Hospital, Lille, Reims University Hospital, University Hospital, Clermont-Ferrand, Assistance Publique Hopitaux De Marseille, Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT04859608
Brief Title
Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (EspacECU)
Acronym
EspacECU
Official Title
Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring: Prospective Health-economic Evaluation in Patients in Remission With Atypical Hemolytic Uraemic Syndrome Requiring Long-term Treatment.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
July 1, 2022 (Anticipated)
Study Completion Date
February 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
Collaborators
Centre Hospitalier Universitaire, Amiens, University Hospital, Angers, Centre Hospitalier Universitaire de Besancon, University Hospital, Caen, Centre Hospitalier of Chartres, Nantes University Hospital, University of Nancy, Poitiers University Hospital, Rennes University Hospital, University Hospital, Rouen, University Hospital, Strasbourg, France, Centre Hospitalier Universitaire de Nice, Hôpital Necker-Enfants Malades, Tenon Hospital, Paris, University Hospital, Lille, Reims University Hospital, University Hospital, Clermont-Ferrand, Assistance Publique Hopitaux De Marseille, Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Eculizumab is an anti-C5 monoclonal antibody approved for rare diseases including atypical haemolytic-uraemic syndrome. The maintenance phase dosing regimen is identical for all adult patients but several studies have shown a high interindividual kinetics variability. A tailored administration of eculizumab based on therapeutic drug monitoring will be compared with real-life administration in adults suffering from an atypical haemolytic uraemic syndrome. The objective is to improve efficiency of eculizumab administration.
Detailed Description
Eculizumab is a very expensive drug (450 000 euros per year per patient). According to the usual administration scheme, the eculizumab is administrated by intravenous infusion, every 14 or 21 days in hospital. Studies have shown the possibility of extending the administration intervals in patients with a high concentration of eculizumab. A personalized spacing of eculizumab infusions, based on a therapeutic drug monitoring, is expected to improve the patient's quality of life and lead to substantial savings. For these reasons, the objective of this study is to explore the efficiency of a personalized spacing of eculizumab infusions compared to the usual administration scheme (without personalization) from the French health Insurance perspective. The efficiency will be assessed by estimating the incremental cost per QALY (Quality-Adjusted Life Year) gained at 18 months (duration of follow-up in the clinical trial) and at 5 years thanks to a Markov model. The total duration of the study is 24 months (6 months of enrolment and 18 months of follow-up).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemolytic-Uremic Syndrome, Atypical
Keywords
Hemolytic-Uremic Syndrome, Kidney Diseases, Thrombotic Microangiopathies, Therapeutic drug monitoring, Eculizumab tailoring, Cost-utility analysis, Markov model

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic drug monitoring
Arm Type
Experimental
Arm Description
Tailored dosing schedule for eculizumab based on therapeutic drug monitoring
Arm Title
Control
Arm Type
No Intervention
Arm Description
Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm.
Intervention Type
Drug
Intervention Name(s)
Spacing of Eculizumab infusions
Intervention Description
Personalized spacing of eculizumab infusions using a pharmacokinetic population model to estimate eculizumab concentration ( a one-week spacing of eculizumab infusion will be decide if predicted eculizumab concentration in the event of spacing is > 150 mg/L). Spacing of infusion can be decided every 3 months.
Primary Outcome Measure Information:
Title
Incremental Cost-Utility Ratio (ICUR) at 18 months of a personalized spacing of eculizumab infusions compared to the usual administration scheme without personalization, from the French health insurance perspective.
Description
The ICUR will express the incremental cost per QALY (Quality-adjusted Life Years) gained over a 18-month time horizon. QALYs will be estimated from patient responses to the EQ-5D-5L instrument (EuroQol group - 5 Dimensions - 5 levels). Costs related to hospital care resources (medicalized information system program), transports (patient diary), eculizumab concentration dosing (cost estimation) will be estimated from the French Health Insurance perspective. Cost and QALY estimates will be used to estimate the within-trial ICUR.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Incremental Cost-Utility Ratio at 5 years (incremental cost per QALY gained) of a personalized spacing of the eculizumab infusions compared to the usual administration scheme without personalization, estimated from a Markov model.
Description
A Markov model will represent the patient's clinical progression across different health states over a 5-year period. Markov modelling will use the within-trial data to estimate the transition probabilities, the state cost and utility values.
Time Frame
5 years
Title
Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions
Description
The financial impact of spreading the strategy of personalized spacing of eculizumab infusions, in patients in remission with atypical hemolytic uraemic syndrome requiring long-term treatment, will be estimated per year and over a 5-year period, from the French Health Insurance (using a budget impact model).
Time Frame
per year and over a 5-year period
Title
Quality of life measured over a 18-month period using different specific scales (KDQoL-SF, ReTransQoL-Version 2) dedicated to patients with renal disease
Description
KDQoL-SF (Kidney Disease and Quality of Life™ Short Form) survey is a kidney-disease-specific quality of life instrument that assesses four domains : health, kidney disease, effects of kidney disease on daily life, satisfaction with care. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. RTQ-V2 (ReTransQoL-Version 2) survey is a specific quality of life instrument for renal transplant recipients. It comprises of 32 items describing five domains: Physical Health, Social Functioning, Medical Care, Treatment and Fear of Losing Graft. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. KDQoL-SF survey will be used for all patients, and RTQ-V2 survey for kidney transplant patients only. The quality of life will be measured every three months.
Time Frame
at baseline, 3, 6, 9, 12, 15 and 18 months.
Title
Determining the factors of intra- and inter- individual variability of eculizumab concentrations.
Description
A study will be performed to determine whether biological and genetic (complement genetic variants reported as cause of HUS) parameters influence trough concentrations of eculizumab
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults with an atypical Hemolytic and Uremic Syndrome defined by at least 2 of the following parameters: Thrombopenia (platelet count < 150 G/L) Mechanical lytic anemia (Hb < 10 g/L, Lactate dehydrogenase > upper limit of normal, undetectable haptoglobin, presence of schistocytes on blood smear) Acute renal failure Eculizumab treatment Without project of withdrawal in the next 18 months Started since at least 6 months Administrated with an unchanged administration schedule since at least 3 months (initial episode or relapse) Atypical Hemolytic and Uremic Syndrome in remission Patients who give informed consent. Exclusion Criteria: Patients on dialysis. Women treated starting or planning a pregnancy. Patients suffering from a typical or secondary microangiopathic hemolytic anemia (drugs, malignancies, autoimmune disease...) Patients under protection of a judicial authority
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GATAULT PHILIPPE, Pr
Phone
02 47 47 37 46
Email
philippe.gatault@univ-tours.fr
Facility Information:
Facility Name
CHU Amiens Picardie
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PRESNE CLAIRE, Dr
Email
Presne.Claire@chu-amiens.fr
Facility Name
CHU d'Angers
City
Angers
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DUVEAU AGNES, Dr
Facility Name
Hôpital Tenon
City
APHP Tenon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BAGNIS CORINNE, DR
Facility Name
CHU Besançon
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DUCLOUX DIDIER, DR
Facility Name
Hôpital de la Côte de Nacre
City
Caen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CHATELET VALERIE, DR
Facility Name
Hôpital Louis Pasteur
City
Chartres
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ALBERT CATHERINE, DR
Facility Name
Hôpital Gabriel Montpied
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PHILIPPONNET CAROLE, DR
Facility Name
Hospices Civils de Lyon
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guebre-Egziabher FITSUM, DR
Facility Name
Hopital de la conception
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BURTEY STEPHANE, DR
Facility Name
Hôpitaux de Brabois
City
Nancy
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LAURAIN EMMANUELLE, DR
Facility Name
Hotel Dieu
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
DELTOMBE CLEMENT, DR
Facility Name
Hopital Necker
City
Necker
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LEGENDRE CHRISTOPHE, DR
Facility Name
Hopital Pasteur 2
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SEITZ-POLSKI BARBARA, DR
Facility Name
Hôpital de la Milétrie
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ECOTIERE LAURE, DR
Facility Name
Hôpital Maison Blanche
City
Reims
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
COLOSIO CHARLOTTE, DR
Facility Name
Hôpital Pontchaillou
City
Rennes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
VIGNEAU CECILE, DR
Facility Name
Hôpital de Bois-Guillaume
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
BERTRAND DOMINIQUE, DR
Facility Name
Nouvel Hôpital Civil
City
Strasbourg
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CAILLARD OHLMANN SOPHIE, DR

12. IPD Sharing Statement

Learn more about this trial

Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (EspacECU)

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