Clinical trial NCT04269408: A Safety and Efficacy Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping
Official title: A Phase IIb: Randomised, Single-Blind, Safety, Tolerability, Efficacy and Pharmacokinetic Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aneurysmal Subarachnoid Hemorrhage
Keywords: NicaPlant
Nicardipine
Lead sponsor: BIT Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: NeuroScios GmbH
name: Data Magik Limited
name: Pharm-Analyt Labor GmbH
First posted: 2020-02-13
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography
timeFrame: day 8 ± 1 after aneurysm rupture
measure: Safety by adverse event recording
timeFrame: trough study completion, an average of 2 years
Secondary outcomes:
measure: Incidence of new cerebral infarcts on computer tomography (CT) of the brain versus post-intervention CT scan
timeFrame: up to day 14 ± 1 after aneurysm rupture
Other outcomes:
measure: Incidence of vasospasm-related morbidity/mortality
timeFrame: within 21 days post aneurysm rupture
measure: Pharmacokinetic profile of NicaPlant® in plasma
timeFrame: within 21 days post aneurysm rupture or within hospitalisation if shorter
measure: Nicardipine levels in cerebrospinal fluid (CSF) (only in patients provided with an external ventricular drain (EVD) at time of CSF removal for medical reasons)
timeFrame: within 21 days post aneurysm rupture or within hospitalisation if shorter
measure: Length of hospital stay
timeFrame: week 52 ± 2 after aneurysm rupture
measure: Modified Rankin Scale
timeFrame: week 12 ± 1 after aneurysm rupture
measure: Modified Rankin Scale
timeFrame: week 52 ± 2 after aneurysm rupture
measure: Glasgow Outcome Scale Extended
timeFrame: week 12 ± 1 after aneurysm rupture
measure: Glasgow Outcome Scale Extended
timeFrame: week 52 ± 2 after aneurysm rupture
measure: Montreal Cognitive Assessment
timeFrame: week 12 ± 1 after aneurysm rupture
measure: Montreal Cognitive Assessment
timeFrame: week 52 ± 2 after aneurysm rupture
measure: EQ-5D-5L
timeFrame: week 12 ± 1 after aneurysm rupture
measure: EQ-5D-5L
timeFrame: week 52 ± 2 after aneurysm rupture
measure: SF36
timeFrame: week 12 ± 1 after aneurysm rupture
measure: SF36
timeFrame: week 52 ± 2 after aneurysm rupture
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie
city: Linz
country: Austria
facility: Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie
city: Vienna
country: Austria
facility: Medizinische Universität Wien, Universitätsklinik für Neurochirurgie
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Klinik für Neurochirurgie mit Arbeitsbereich pädiatrische Neurochirurgie
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen, Neurochirurgische Klinik
city: Munich
country: Germany
facility: Klinikum Rechts der Isar, Neurochirurgische Klinik und Poliklinik
Study officials:
affiliation: Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie
name: Claudius Thomé, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References: