Hemolytic-Uremic Syndrome, AtypicalPhase 3EspacECUNCT04859608
Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (EspacECU)
A Phase 3 study testing Spacing of Eculizumab infusions in people with Hemolytic-Uremic Syndrome, Atypical, run by University Hospital, Tours at 18 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemolytic-Uremic Syndrome, Atypical
- What is being tested?
- Spacing of Eculizumab infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 18 sitesFrance
- Study dates
- 20 Oct 2021to 28 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
France18 sites
CHU Amiens Picardie
Amiens
CHU d'Angers
Angers
Hôpital Tenon
APHP Tenon
CHU Besançon
Besançon
Hôpital de la Côte de Nacre
Caen
Hôpital Louis Pasteur
Chartres
Hôpital Gabriel Montpied
Clermont-Ferrand
Hospices Civils de Lyon
Lyon
Hopital de la conception
Marseille
Hôpitaux de Brabois
Nancy
Hotel Dieu
Nantes
Hopital Necker
Necker
Hopital Pasteur 2
Nice
Hôpital de la Milétrie
Poitiers
Hôpital Maison Blanche
Reims
Hôpital Pontchaillou
Rennes
Hôpital de Bois-Guillaume
Rouen
Nouvel Hôpital Civil
Strasbourg
About this study
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.
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.
Read the 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).
- Conditions
- Hemolytic-Uremic Syndrome, Atypical
- Being tested
- Spacing of Eculizumab infusions
- Keywords
- Hemolytic-Uremic Syndrome, Kidney Diseases, Thrombotic Microangiopathies, Therapeutic drug monitoring, Eculizumab tailoring, Cost-utility analysis, Markov model
- Medical subject headings
- Atypical Hemolytic Uremic Syndrome, Hemolytic-Uremic Syndrome, Kidney Diseases, Thrombotic Microangiopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spacing of Eculizumab infusionsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic drug monitoring | Experimental | Tailored dosing schedule for eculizumab based on therapeutic drug monitoring Receives: Drug: Spacing of Eculizumab infusions |
| Control | No intervention | Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (4)
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.
Measured: 5 years
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).
Measured: per year and over a 5-year period
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.
Measured: at baseline, 3, 6, 9, 12, 15 and 18 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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2021
- Study start20 Oct 2021
- Primary completion16 Jun 2022
- Study completion28 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemolytic-Uremic Syndrome, AtypicalStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized (2:1) controlled study, open-label, with Markov modeling.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04859608
- Sponsor's protocol ID
- DR200088-EspacECU
- Acronym
- EspacECU
- Status last verified
- Mar 2025
- First submitted
- 2 Feb 2021
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04859608
- Acronym / sponsor ID
- EspacECU / DR200088-EspacECU
- Conditions
- Hemolytic-Uremic Syndrome, Atypical
- Keywords
- Hemolytic-Uremic Syndrome, Kidney Diseases, Thrombotic Microangiopathies, Therapeutic drug monitoring, Eculizumab tailoring, Cost-utility analysis, Markov model
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- 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
- Study start
- 20 Oct 2021 (actual)
- Primary completion
- 16 Jun 2022 (actual)
- Study completion
- 28 Dec 2023 (actual)
- First posted
- 26 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized (2:1) controlled study, open-label, with Markov modeling.
| Arm | Type | Receives |
|---|---|---|
| Therapeutic drug monitoring | Experimental | Drug: Spacing of Eculizumab infusionsTailored dosing schedule for eculizumab based on therapeutic drug monitoring |
| Control | No intervention | –Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults with an atypical Hemolytic and Uremic Syndrome defined by at least 2 of the following parameters:
- Eculizumab treatment
- Atypical Hemolytic and Uremic Syndrome in remission
- Patients who give informed consent.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spacing of Eculizumab infusionsPersonalized 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. | Drug | Therapeutic drug monitoring |
Primary outcome
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.
Time frame: 18 months
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.
4 secondary outcomes
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.
Time frame: 5 years
Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions
Time frame: per year and over a 5-year period
Quality of life measured over a 18-month period using different specific scales (KDQoL-SF, ReTransQoL-Version 2) dedicated to patients with renal disease
Time frame: at baseline, 3, 6, 9, 12, 15 and 18 months.
Determining the factors of intra- and inter- individual variability of eculizumab concentrations.
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Spacing of Eculizumab infusions in people with Hemolytic-Uremic Syndrome, Atypical, run by University Hospital, Tours at 18 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.