Aneurysmal subarachnoid haemorrhage MedDRA version: 20.1 Level: PT Classification code 10008111 Term: Cerebral haemorrhage System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: NicaPlant®
Pharmaceutical Form: Implant
INN or Proposed INN: NICARDIPINE
CAS Number: 55985-32-5
Concentration unit: mg mil
Sponsors
BIT Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent is obtained. 2. Male or female patients aged 18 to 75 years (inclusive). 3. Federation of Neurosurgery (WFNS) grade I-IV or Hunt & Hess grade I-IV. 4. Ruptured saccular aneurysm, confirmed by angiography. 5. Onset of aSAH clinical symptoms within the preceding 48 hours. 6. Treatment of aneurysm via surgical clip ligation within 72 hours of aSAH is achievable. 7. 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 during the study and up to 2 months 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 during the study and up to 4 months after implantation of the study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. SAH due to other causes (e.g. trauma, fusiform or mycotic aneurysm). 2. Pregnant or lactating Women. 3. Federation of Neurosurgery (WFNS) grade V or Hunt & Hess grade V. 4. Intraventricular or intracerebral blood, in the absence of subarachnoid blood. 5. Treatment of aneurysm via endovascular embolization. 6. Presence of moderate or severe vasospasm on screening angiography. 7. Any known or CT evidence of previous major cerebral damage. 8. Evidence of a cerebral infarction with neurological deficit on pre-treatment CT. 9. 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. 10. Patients who have received an investigational product or participated in another interventional clinical study within 30 days prior to randomisation. 11. Kidney disease as defined by plasma creatinine =2.5mg/dL (221µmol/L); liver disease as defined by total bilirubin >3mg/dL (513µmol/L); and/or known diagnosis or clinical suspicion of liver cirrhosis. 12. Patients with known allergy for Poly (D,L-lactide-co-glycolide) (PLGA) or nicardipine. 13. 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 |
|---|---|
| Main Objective: To investigate the safety and tolerability of single ascending doses (as number of implants/patient) of local nicardipine application via polymers (NicaPlant®).; Secondary Objective: • To assess the pharmacokinetics of single ascending doses (as number of implants/patient) of NicaPlant® in Plasma, and its levels in CSF. • To take exploratory measurements of clinical efficacy in terms of: o Incidence of moderate or severe cerebral angiographic vasospasm assessed by digital subtraction angiography (DSA) at 8±1 days after aneurysm rupture. o Incidence of vasospasm-related morbidity/mortality within 14 days post-aneurysm rupture. o Incidence of new cerebral infarcts on computed tomography (CT) scan performed at day 14 post-aneurysm rupture versus post-treatment CT scan. ; Primary end point(s): Safety: • Adverse events (AEs) • Occurrence of shunt-dependent hydrocephalus • Occurrence of bacterial meningitis • Change in grading of AE severity • Vital Signs: blood pressure (BP), pulse rate, respiratory rate and body temperature • Electrocardiogram (ECG) • Full blood count, urea and electrolytes, liver function tests, C-reactive protein ;Timepoint(s) of evaluation of this end point: Safety assessments will be made from baseline until day 21±1, daily or on alternate days. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory endpoint Incidence of moderate or severe cerebral angiographic vasospasm assessed by digital subtraction angiography (DSA) at 8±1 days after aneurysm rupture, where angiographic vasospasm is defined as a =33% reduction in diameter in at least one vessel segment by comparison to preoperative (and pre NicaPlant® implantation) angiography. The day 8±1 angiogram will be performed even if the patient has no clinical or sonographic evidence of vasospasm. Other exploratory endpoints 1. Incidence of vasospasm-related morbidity/mortality within 21 days post-aneurysm rupture, defined by at least one of the following: a. Delayed ischemic neurological deficit (DIND) – confirmed by mGCS. b. Death caused by vasospasm, DIND, infarcts or complications due to anti-vasospasm therapy. 2. Incidence of new cerebral infarcts on CT scan performed at Day 14 ± 1 post-aneurysm rupture versus post-treatment CT scan. 3. The need for anti-vasospasm rescue therapy within 14 days post-aneurysm rupture. 4. Daily assessment of modified Glasgow Coma Scale (mGCS) up to Day 21. Pharmacokinetics (PK): Only samples collected in patients treated with NicaPlant® will be analysed at the end of this study. Pharmacodynamics (PD): The PD endpoints are angiographic measurements of cerebral vasospasm, DIND and new cerebral infarcts on CT scan. ; Timepoint(s) of evaluation of this end point: Exploratory endpoint 8±1 days after aneurysm rupture. If the patient develops clinical or sonographic changes suggestive of vasospasm prior to day 8, an angiogram will be performed and replaces the one scheduled at day 8±1. Other exploratory endpoints 1. Within 21 days post-aneurysm rupture | — |
Countries
Austria
Contacts
Public ContactCRO
NeuroScios GmbH
Outcome results
None listed