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van CCT (UK)

van CCT (UK)

Inflammation inhibitors to reduce brain injury after a hemorrhagic stroke.

- candidate number28111
- NTR NumberNTR6752
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR27-okt-2017
- Secondary IDsNL-63723 
- Public TitleInflammation inhibitors to reduce brain injury after a hemorrhagic stroke.
- Scientific TitleComplement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Hemorrhage: safety and proof-of-concept
- hypothesisTreatment with C5 antibodies decreases early brain injury and delayed cerebral ischemia in patients with aneurysmal SAH and thereby improves clinical condition.
- Healt Condition(s) or Problem(s) studiedSubarachnoid hemorrhage (SAH), Early brain injury, Delayed cerebral ischemia
- Inclusion criteria1) Confirmed aneurysmal SAH
2) Admission to either the UMCU or Erasmus MC within 5.5 hours after ictus
3) WFNS score of 2-5 on admission
4) Age 18 years and older
- Exclusion criteria1) Life expectancy < 10 days;
2) Pregnant or breast-feeding women;
3) Participation in another clinical therapeutic study;
4) History of splenectomy or asplenia (potentially increased risk of meningococcal infection); 5) Hematologic malignancy;
6) Patients receiving chemotherapy;
7) Patients with myasthenia gravis, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or tuberculosis;
8) Patients who are or will be treated by plasmapheresis or hemodialysis;
9) Patient with a creatinine clearance of <30 or serum creatinine levels of >169 μmol/l;
10) Patients with a known hereditary complement deficiency;
11) Patients allergic to eculizumab, proteins derived from mouse products or other monoclonal antibodies;
12) Patients allergic to (prophylactic) antibiotic treatment for Neisseria meningitidis (quinolones or ceftriaxone (therapeutic));
13) If on admission, it is likely that the aneurysm can only be treated with extracranial-intracranial bypass surgery;
14) If based on head imaging, it will be unlikely that CSF can be obtained 48-72 hours after ictus;
15) Patients with an ongoing infection on admission which is not appropriately treated;
16) Patients who are currently treated with methotrexate, tizanidine, tacrolimus, belimumab, denosumab, fingolimod, leflunomide, natalixumab, pimecrolimus, roflumilast, sipuleucel-T, tofacitinib or trastuzumab.
- mec approval receivedyes
- multicenter trialyes
- randomisedyes
- masking/blindingNone
- controlActive
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-aug-2018
- planned closingdate1-aug-2020
- Target number of participants40
- InterventionsThe intervention group will receive intravenous eculizumab infusions.
- Primary outcomeThe primary outcome measure is biological effectivity determined by the C5a concentration in CSF.
- Secondary outcome2) Occurrence of AEs and SAEs;
3) Blood plasma and CSF parameters of inflammation (e.g. CRP and cytokines);
4) Concentration of eculizumab in blood plasma and CSF;
5) Daily neurological condition measured by GCS during the first fourteen days of hospital stay;
6) Neurological condition measured by the NIHSS and WFNS score 14 days after ictus;
7) Cerebral infarction on brain MRI at hospital discharge;
8) Cognition and QoL ten weeks (+/- two weeks) after ictus;
9) The mRS thirteen weeks (+/- two weeks) after ictus.
- TimepointsPrimary outcome measure:
1) 48-72 hours after ictus

Secondary outcome measurements:
2) Four weeks;
3 & 4) Blood plasma during hospital stay at multiple timepoints (on admission and on day 2, 4, 6, 9, 12 and 14). CSF 48-72 hours after ictus;
5) Daily during the first fourteen days of the hospital stay;
6) On day 14;
7) At discharge;
8) Ten weeks after ictus (+/- two week);
9) Thirteen weeks after ictus (+/- two weeks).
- Trial web site
- statusplanned
- Sponsor/Initiator University Medical Center Utrecht (UMCU)
- Funding
(Source(s) of Monetary or Material Support)
ZonMw, Alexion Pharmaceuticals
- Publications
- Brief summaryImportant determinants of poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH) are early brain injury (brain injury <72 hours after ictus) and delayed cerebral ischemia (4-14 days after the bleeding). No treatment exists to reduce early brain injury and the effects of current strategies (nimodipine, euvolemia) to prevent delayed cerebral ischemia are only modest. The inflammatory response is considered to play a key role in the pathogenesis of early brain injury and delayed cerebral ischemia after aneurysmal SAH. Previous studies found that the complement cascade is activated in patients with SAH and associated with poor functional outcome. Eculizumab is a complement C5 inhibitor that prevents the formation of C5a and C5b. In the current trial, we will investigate the biological effect and safety of eculizumab in patients with aneurysmal SAH.
- Main changes (audit trail)- Masking/blinding: Open-label with blinded outcome assessment (PROBE design)
- Control: care as usual
- RECORD27-okt-2017 - 22-jun-2018

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