A Safety and Efficacy Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase IIb: Randomised, Single-Blind, Safety, Tolerability, Efficacy and Pharmacokinetic Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Nicardipine
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NicaPlant®<br>10 NicaPlant® implants (total 40 mg nicardipine) will be placed after clip ligation into the basal cisterns in direct contact with the exposed cerebral blood vessel walls. In addition patients will receive standard of care for aneurysmal subarachnoid haemorrhage patients according to the treatment guidelines. | Drug: Nicardipine<br>* 10 NicaPlant® implants releasing 4 mg nicardipine each.<br>* Other names: NicaPlant®;Other: Standard of care<br>* Both arms receive the usual standard of care.<br>|
| Other: Control<br>Standard of care for aneurysmal subarachnoid haemorrhage patients according to the treatment guidelines. | Other: Standard of care<br>* Both arms receive the usual standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography | Fishers Exact test | day 8 ± 1 after aneurysm rupture | 
| Safety by adverse event recording | Descriptive summary | trough study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new cerebral infarcts on computer tomography (CT) of the brain versus post-intervention CT scan | Fishers exact test | up to day 14 ± 1 after aneurysm rupture | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NicaPlant, Nicardipine