Aneurysmal Subarachnoid Hemorrhage
Conditions
Keywords
NicaPlant, Nicardipine
Brief summary
This study of NicaPlant® is conducted in patients who have a subarachnoid haemorrhage. Patients will be randomized in two treatment groups. Both groups will receive the standard of care and the investigational group will receive in addition NicaPlant®. NicaPlant® is tested to reduce the long-term complications of aneurysmal subarachnoid haemorrhage (aSAH).
Detailed description
This is a safety, tolerability, efficacy and pharmacokinetic study of NicaPlant® in subarachnoid haemorrhage patients involving two treatment groups. Both treatment groups will receive standard of care and patients randomised to the investigational group will receive in addition NicaPlant® . NicaPlant® is a nicardipine modified-release formulation. It is presented in the form of a rod-shaped implant with a 4 mg nicardipine load. Following aneurysm clip ligation, 10 NicaPlant® implants will be placed into the basal cisterns in direct contact with the exposed cerebral blood vessel walls.
Interventions
DRUGNicardipine
10 NicaPlant® implants releasing 4 mg nicardipine each.
OTHERStandard of care
Both arms receive the usual standard of care.
Sponsors
NeuroScios GmbH
Data Magik Limited
Pharm-Analyt Labor GmbH
BIT Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
The clinical trial is defined as a single-blind study. For ethical reasons, no placebo implants will be used and therefore the surgeon cannot be blinded. All investigators/surgeons who have not been involved in the operation of a patient will remain blinded for this particular patient.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained according to the Country regulation. * Male or female patients aged 18 to 75 years (inclusive). * World Federation of Neurological Surgeons (WFNS) grade III-IV. * Ruptured saccular aneurysm, confirmed by angiography. * Onset of aSAH clinical symptoms within the preceding 48 hours. * Treatment of aneurysm via surgical clip ligation within 72 hours of aSAH is achievable. * Female patients of child-bearing potential must have a negative pregnancy test (urine or serum) at screening and must agree to use adequate birth control up to 12 weeks after implantation of the study drug. Female patients are considered to be not of child-bearing potential if they have a history of tubal ligation or hysterectomy or are post-menopausal with a minimum of 2 years without a natural menstrual cycle. Male patients must agree to use adequate birth control up to 12 weeks after implantation of the study drug.
Exclusion criteria
* SAH due to other causes (e.g. trauma, fusiform or mycotic aneurysm). * World Federation of Neurosurgery (WFNS) grade I, II and V patients. * Pregnant or Lactating Women. * Intraventricular or intracerebral blood, in the absence of subarachnoid blood. * Treatment of aneurysm via endovascular embolisation. * Presence of moderate or severe vasospasm on screening angiography. * Any known or CT /MRI evidence of previous major cerebral damage * Evidence of a cerebral infarction with neurological deficit on pre-treatment CT/MRI. * History of malignant disease (except for non-melanoma skin cancer) within the previous 5 years or any history of malignant brain tumours or brain metastasis. * Patients who have received an investigational product or participated in another interventional clinical study within 30 days prior to randomisation. * Patients with known allergy for Poly(D,L-lactide-co-glycolide) (PLGA) or nicardipine. * Major complication during aneurysm repair such as, but not limited to, massive intraoperative haemorrhage, brain swelling, or inability to secure the ruptured aneurysm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography | day 8 ± 1 after aneurysm rupture | Fishers Exact test |
| Safety by adverse event recording | trough study completion, an average of 2 years | Descriptive summary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of new cerebral infarcts on computer tomography (CT) of the brain versus post-intervention CT scan | up to day 14 ± 1 after aneurysm rupture | Fishers exact test |
Other
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | week 52 ± 2 after aneurysm rupture | ANOVA |
| Modified Rankin Scale | week 12 ± 1 after aneurysm rupture | Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 0, maximum value: 6, higher scores mean a worse outcome |
| Glasgow Outcome Scale Extended | week 12 ± 1 after aneurysm rupture | Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 1, maximum value: 8, higher scores mean a better outcome |
| Incidence of vasospasm-related morbidity/mortality | within 21 days post aneurysm rupture | Fishers exact test |
| EQ-5D-5L | week 12 ± 1 after aneurysm rupture | ANOVA |
| SF36 | week 12 ± 1 after aneurysm rupture | ANOVA |
| Montreal Cognitive Assessment | week 12 ± 1 after aneurysm rupture | ANOVA minimum value: 0, maximum value: 30, higher scores mean a better outcome |
| Pharmacokinetic profile of NicaPlant® in plasma | within 21 days post aneurysm rupture or within hospitalisation if shorter | AUC for multiple plasma samples |
| Nicardipine levels in cerebrospinal fluid (CSF) (only in patients provided with an external ventricular drain (EVD) at time of CSF removal for medical reasons) | within 21 days post aneurysm rupture or within hospitalisation if shorter | Average concentration (Cav) for single CSF samples if sufficient CSF data is obtained. |
Countries
Austria, Germany
Outcome results
None listed