Clinical trial NCT04859608: Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemolytic-Uremic Syndrome, Atypical
Keywords: Hemolytic-Uremic Syndrome
Kidney Diseases
Thrombotic Microangiopathies
Therapeutic drug monitoring
Eculizumab tailoring
Cost-utility analysis
Markov model
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire, Amiens
name: University Hospital, Angers
name: Centre Hospitalier Universitaire de Besancon
name: University Hospital, Caen
name: Centre Hospitalier of Chartres
name: Nantes University Hospital
name: University of Nancy
name: Poitiers University Hospital
name: Rennes University Hospital
name: University Hospital, Rouen
name: University Hospital, Strasbourg, France
name: Centre Hospitalier Universitaire de Nice
name: Hôpital Necker-Enfants Malades
name: Tenon Hospital, Paris
name: University Hospital, Lille
name: Reims University hospital
name: University Hospital, Clermont-Ferrand
name: Assistance Publique Hopitaux De Marseille
name: Hospices Civils de Lyon
First posted: 2021-04-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (2:1) controlled study, open-label, with Markov modeling.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 18 months
Secondary outcomes:
measure: 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.
timeFrame: 5 years
measure: Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions
timeFrame: per year and over a 5-year period
measure: Quality of life measured over a 18-month period using different specific scales (KDQoL-SF, ReTransQoL-Version 2) dedicated to patients with renal disease
timeFrame: at baseline, 3, 6, 9, 12, 15 and 18 months.
measure: Determining the factors of intra- and inter- individual variability of eculizumab concentrations.
timeFrame: 5 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: CHU d'Angers
city: APHP Tenon
country: France
facility: Hôpital Tenon
city: Besançon
country: France
facility: CHU Besançon
city: Caen
country: France
facility: Hôpital de la Côte de Nacre
city: Chartres
country: France
facility: Hôpital Louis Pasteur
city: Clermont-Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Hopital de la conception
city: Nancy
country: France
facility: Hôpitaux de Brabois
city: Nantes
country: France
facility: Hotel Dieu
city: Necker
country: France
facility: Hopital Necker
city: Nice
country: France
facility: Hopital Pasteur 2
city: Poitiers
country: France
facility: Hôpital de la Milétrie
city: Reims
country: France
facility: Hôpital Maison Blanche
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Hôpital de Bois-Guillaume
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
Study officials:
References: