Hypertensive Emergency-associated Hemolytic Uremic SyndromePhase 3HYPERSHUNCT05726916
Eculizumab in Hypertensive Emergency-associated Hemolytic Uremic Syndrome
A Phase 3 study testing Soliris® and Renin angiotensin system blockers in people with Hypertensive Emergency-associated Hemolytic Uremic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Hemolytic and uremic syndrome (HUS) is a clinic-biological syndrome related to thrombotic microangiopathy affecting predominantly the kidney. Atypical HUS (aHUS) has been historically defined as HUS occurring in the absence of infectious event. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertensive Emergency-associated Hemolytic Uremic Syndrome
- What is being tested?
- Soliris® and Renin angiotensin system blockers
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteFrance
- Study dates
- 9 Nov 2023to 9 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- ≥ 18years
- Hospitalization for HE-aHUS within prior 10 days:
- Presume acute renal failure (renal replacement therapy or serum creatinine ≥ 354µM)
- Mechanical hemolysis including: anemia, thrombopenia, and: low haptoglobin (<LNL), or elevated LDH (>1,5UNL), or presence of schistocytes
- Severe hypertension with systolic blood pressure >180mmHg or diastolic blood pressure>110mmHg
- Target organ damage, including neurological involvement (notably hypertensive encephalopathy, headache, confusion, nausea, posterior reversible encephalopathy syndrome), or cardiovascular involvement (notably acute left ventricular failure, acute pulmonary edema, acute cardiac ischemia, chest pain, dyspnea, palpitations), or ophtalmological involvement (notably ischemic retinopathy or blurred vision)
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- Effective contraception during the study and for at least 5 months after the last dose of treatment with eculizumab
- Subject affiliated to a social security regimen
- Subject having signed written informed consent.
Who cannot join
- Atrophic kidneys with maximum length<8cm on recent (<1 month) renal ultrasound, CT scan, or renal MRI
- High clinical suspicion of Complement-mediated aHUS (including familial history of aHUS)
- High clinical suspicion of typical HUS (including Shiga Toxin-producing E. Coli infection) or Thrombotic thrombocytopenic purpura
- High clinical suspicion of secondary HUS related to autoimmune disease (including lupus, scleroderma, antiphospholipid syndrome, ANCA vasculitis), or C3 glomerulopathy.
- High clinical suspicion of recent hemorrhagic or ischemic stroke.
- ADAMTS 13<10%, HIV or HCV infection, positivity of 2 markers among: anticardiolipin IgG/antiBeta2 GP1 IgG/lupus anticoagulant, positivity of ANCA (ELISA PR3 or MPO)
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- Active infection
- Subjects with unresolved Neisseria meningitidis infection
- Subjects refusing Neisseria meningitidis vaccination or refusing antibioprophylaxis with oracillin (In case of penicillin allergy, antibioprophylaxis with macrolide couldbeproposed according to ANSM recommendations (azithromycin or roxithromycin)).
- Contra-indication to eculizumab or renin angiotensin system blockers
- Solid organ or haematopoietic transplant
- History (<1year) of active cancer or exposition to drugs associated with aHUS (< 3 months)
- Severe cognitive or psychiatric disorders, patients unable to give an informed consent.
- PCR SARS-CoV2 positive
- Pregnant or breastfeeding woman or ineffective contraception
- Persons deprived of their liberty by judicial or administrative decision,
- Persons under legal protection (guardianship, curatorship)
- Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Tenon Hospital
Paris, 75020
Khalil EL KAROUI, Doctor (MD), 01 56 01 63 17 ext. +33, khalil.el-karoui@aphp.fr
About this study
Official title: Eculizumab in Hypertensive Emergency-associated Hemolytic Uremic Syndrome: a Randomized Multicenter Controlled Trial
Hemolytic and uremic syndrome (HUS) is a clinic-biological syndrome related to thrombotic microangiopathy affecting predominantly the kidney. Atypical HUS (aHUS) has been historically defined as HUS occurring in the absence of infectious event. The role of complement dysregulation in aHUS pathophysiology has been largely demonstrated, since C genetic rare variants are present in 60-70% aHUS patients. In line with the frequency of C dysregulation in aHUS, Eculizumab, an anti-C5 monoclonal antibody, has dramatically improved aHUS patients prognosis.
Numerous conditions have been associated with aHUS, including hypertensive emergency (HE), a syndrome of acute blood pressure flare associated with end-organ damage. In cases of HE-aHUS, whether primary aHUS is complicated by secondary HE, or primary HE leads to secondary aHUS is still debated.
Read more
The investigators recently demonstrated that C genetic variants frequency was similar in patients with HE-aHUS and patients with aHUS without HE, suggesting a major role for C dysregulation in HE-aHUS. Consequently, the investigators propose to evaluate, in HE-aHUS patients, the benefit of a strategy with early Eculizumab therapy (used within its marketing authorization and its conditions of refunding by the health insurance in usual care), compared to standard of care including tight blood pressure control.
The hypothesis suggests that C dysregulation may impact renal prognosis of HE-aHUS patients. The investigator's aim to demonstrate that early Eculizumab therapy improves prognosis of HE-aHUS patients.
Method
The HYPERSHU study is a randomized, controlled, open-labelled study including HE-aHUS patients with severe AKI and no evidence of other conditions associated with HUS (infections, autoimmunity, drugs, pregnancy). The investigators plan to include 62 patients. Patients will be randomized in 2 arms:
- Early Eculizumab therapy (for 3 months) added to standard of care (tight blood pressure control).
- Standard of care alone with tight blood pressure control. Renal function after 6 months is the primary evaluation criterium.
HE is a frequently associated with aHUS, and strongly impacts patient renal prognosis. Efficient therapeutic strategies are still lacking for this condition. The HYPERSHU study will allow to evaluate the benefit of early Eculizumab therapy in patients with HE-aHUS and severe renal dysfunction.
- Being tested
- Soliris®, Renin angiotensin system blockers
- Keywords
- Eculizumab, Hypertensive emergency, atypical hemolytic uremic syndrome, complement, acute kidney injury, end stage renal disease
- Medical subject headings
- Hypertensive Crisis, Atypical Hemolytic Uremic Syndrome, Acute Kidney Injury, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Soliris®Drug
Also called Eculizumab
Eculizumab IV administration (900mg/w during 4w then 1200 mg at w5 and 1200mg/2w for 8w) + Blood pressure control with renin angiotensin system blockers
Renin angiotensin system blockersDrug
Blood pressure control with renin angiotensin system blockers
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Eculizumab IV administration (900mg/w during 4w then 1200 mg at w5 and 1200mg/2w for 8w) + Blood pressure control with renin angiotensin system blockers Receives: Drug: Soliris® |
| Control group | Active comparator | Blood pressure control with renin angiotensin system blockers Receives: Drug: Renin angiotensin system blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month response to therapy
6-month response to therapy, as defined by the absence of any of the following events: i) lack of renal efficacy at 6-month follow-up: persistent renal replacement therapy, eGFR <15ml/mn/1,73m2, or patient death; ii) lack of early hemolysis control with persistent hemolysis at W2 despite well conducted antihypertensive therapy. Any Eculizumab rescue in the control group will be considered as a failure.
Measured: 6 month
Secondary outcomes (9)
Frequency of Complement genetic rare variants
Measured: up to 12 months
Rate of renal replacement therapy
Evaluation of renal replacement therapy need at Week 13 and months 12
Measured: Week 13 and 12 months
Frequency of severe infections
defined by the need for hospitalization
Measured: up to 12 months
Time to resolution of hemolysis
Evaluation of hemolysis markers (anamia, thrombocytopenia, low hatoglobin, elevated lacticodehydrogenase, schistocytes)
Measured: up to 12 months
Frequency of kidney lesions
Measured: up to 12 months
Costs relating to renal replacement therapy (or lack of)
Measured: up to 12 months
Costs relating to Eculizumab therapy
Measured: up to 12 months
Costs relating to other antihypertensive treatments
Measured: up to 12 months
Costs relating to hospitalizations
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start9 Nov 2023
- Primary completion9 May 2026 (estimated)
- Study completion9 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertensive Emergency-associated Hemolytic Uremic SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- The present proposal is a randomized, controlled, multicenter, open-labelled study. In the experimental group, Ecu will be administered at randomization according to usual recommendations in aHUS (4 intravenous administrations, 900mg/w until W4 then 1200mg/2w starting at W5, until W13). In both experimental and control group, BP control with systematic maximum tolerated dose of RAS blockers will be administered.
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05726916
- Sponsor's protocol ID
- APHP211039
- Acronym
- HYPERSHU
- Status last verified
- Sep 2023
- First submitted
- 16 Dec 2022
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eculizumab in Hypertensive Emergency-associated Hemolytic Uremic Syndrome: a Randomized Multicenter Controlled Trial
- ClinicalTrials.gov ID
- NCT05726916
- Acronym / sponsor ID
- HYPERSHU / APHP211039
- Keywords
- Eculizumab, Hypertensive emergency, atypical hemolytic uremic syndrome, complement, acute kidney injury, end stage renal disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Nov 2023 (actual)
- Primary completion
- 9 May 2026 (estimated)
- Study completion
- 9 Nov 2027 (estimated)
- First posted
- 14 Feb 2023 (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.
Hemolytic and uremic syndrome (HUS) is a clinic-biological syndrome related to thrombotic microangiopathy affecting predominantly the kidney. Atypical HUS (aHUS) has been historically defined as HUS occurring in the absence of infectious event. The role of complement dysregulation in aHUS pathophysiology has been largely demonstrated, since C genetic rare variants are present in 60-70% aHUS patients. In line with the frequency of C dysregulation in aHUS, Eculizumab, an anti-C5 monoclonal antibody, has dramatically improved aHUS patients prognosis.
Numerous conditions have been associated with aHUS, including hypertensive emergency (HE), a syndrome of acute blood pressure flare associated with end-organ damage. In cases of HE-aHUS, whether primary aHUS is complicated by secondary HE, or primary HE leads to secondary aHUS is still debated.
The investigators recently demonstrated that C genetic variants frequency was similar in patients with HE-aHUS and patients with aHUS without HE, suggesting a major role for C dysregulation in HE-aHUS. Consequently, the investigators propose to evaluate, in HE-aHUS patients, the benefit of a strategy with early Eculizumab therapy (used within its marketing authorization and its conditions of refunding by the health insurance in usual care), compared to standard of care including tight blood pressure control.
The hypothesis suggests that C dysregulation may impact renal prognosis of HE-aHUS patients. The investigator's aim to demonstrate that early Eculizumab therapy improves prognosis of HE-aHUS patients.
Method
The HYPERSHU study is a randomized, controlled, open-labelled study including HE-aHUS patients with severe AKI and no evidence of other conditions associated with HUS (infections, autoimmunity, drugs, pregnancy). The investigators plan to include 62 patients. Patients will be randomized in 2 arms:
- Early Eculizumab therapy (for 3 months) added to standard of care (tight blood pressure control).
- Standard of care alone with tight blood pressure control. Renal function after 6 months is the primary evaluation criterium.
HE is a frequently associated with aHUS, and strongly impacts patient renal prognosis. Efficient therapeutic strategies are still lacking for this condition. The HYPERSHU study will allow to evaluate the benefit of early Eculizumab therapy in patients with HE-aHUS and severe renal dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The present proposal is a randomized, controlled, multicenter, open-labelled study. In the experimental group, Ecu will be administered at randomization according to usual recommendations in aHUS (4 intravenous administrations, 900mg/w until W4 then 1200mg/2w starting at W5, until W13). In both experimental and control group, BP control with systematic maximum tolerated dose of RAS blockers will be administered.
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: Soliris®Eculizumab IV administration (900mg/w during 4w then 1200 mg at w5 and 1200mg/2w for 8w) + Blood pressure control with renin angiotensin system blockers |
| Control group | Active comparator | Drug: Renin angiotensin system blockersBlood pressure control with renin angiotensin system blockers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 18years
- Hospitalization for HE-aHUS within prior 10 days:
- Effective contraception during the study and for at least 5 months after the last dose of treatment with eculizumab
- Subject affiliated to a social security regimen
- Subject having signed written informed consent.
Key exclusion criteria (18 listed)
- Atrophic kidneys with maximum length<8cm on recent (<1 month) renal ultrasound, CT scan, or renal MRI
- High clinical suspicion of Complement-mediated aHUS (including familial history of aHUS)
- High clinical suspicion of typical HUS (including Shiga Toxin-producing E. Coli infection) or Thrombotic thrombocytopenic purpura
- High clinical suspicion of secondary HUS related to autoimmune disease (including lupus, scleroderma, antiphospholipid syndrome, ANCA vasculitis), or C3 glomerulopathy.
- High clinical suspicion of recent hemorrhagic or ischemic stroke.
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 |
|---|---|---|
| Soliris®Also: EculizumabEculizumab IV administration (900mg/w during 4w then 1200 mg at w5 and 1200mg/2w for 8w) + Blood pressure control with renin angiotensin system blockers | Drug | Experimental group |
| Renin angiotensin system blockersBlood pressure control with renin angiotensin system blockers | Drug | Control group |
Primary outcome
6-month response to therapy
Time frame: 6 month
6-month response to therapy, as defined by the absence of any of the following events: i) lack of renal efficacy at 6-month follow-up: persistent renal replacement therapy, eGFR <15ml/mn/1,73m2, or patient death; ii) lack of early hemolysis control with persistent hemolysis at W2 despite well conducted antihypertensive therapy. Any Eculizumab rescue in the control group will be considered as a failure.
9 secondary outcomes
Frequency of Complement genetic rare variants
Time frame: up to 12 months
Rate of renal replacement therapy
Time frame: Week 13 and 12 months
Frequency of severe infections
Time frame: up to 12 months
Time to resolution of hemolysis
Time frame: up to 12 months
Frequency of kidney lesions
Time frame: up to 12 months
Costs relating to renal replacement therapy (or lack of)
Time frame: up to 12 months
Costs relating to Eculizumab therapy
Time frame: up to 12 months
Costs relating to other antihypertensive treatments
Time frame: up to 12 months
Costs relating to hospitalizations
Time frame: up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Individual participant dataSharing planned: No. DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Soliris® and Renin angiotensin system blockers in people with Hypertensive Emergency-associated Hemolytic Uremic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 9 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month response to therapy (time frame: 6 month). 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 5 Jan 2024.