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

Aneurysmal Subarachnoid Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04269408
• Other study ID #: BIT-002
• Secondary ID: 2017-005159-10
• Status: Completed
• Phase: Phase 2
• Start date: April 5, 2020
• Est. completion date: January 23, 2023

Study information

• Verified date: July 2023
• Source: BIT Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 23, 2023
• Est. primary completion date: May 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aneurysm
• Aneurysmal Subarachnoid Hemorrhage
• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

Drug:
• Nicardipine
10 NicaPlant® implants releasing 4 mg nicardipine each.

Other:
• Standard of care
Both arms receive the usual standard of care.

Locations

Country	Name	City	State
Austria	Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie	Innsbruck
Austria	Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie	Linz
Austria	Medizinische Universität Wien, Universitätsklinik für Neurochirurgie	Vienna
Germany	Charité Universitätsmedizin Berlin, Klinik für Neurochirurgie mit Arbeitsbereich pädiatrische Neurochirurgie	Berlin
Germany	Universitätsklinikum Göttingen, Neurochirurgische Klinik	Göttingen
Germany	Klinikum Rechts der Isar, Neurochirurgische Klinik und Poliklinik	Munich

Sponsors (4)

Lead Sponsor	Collaborator
BIT Pharma GmbH	Data Magik Limited, NeuroScios GmbH, Pharm-Analyt Labor GmbH

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of vasospasm-related morbidity/mortality	Fishers exact test	within 21 days post aneurysm rupture
Other	Pharmacokinetic profile of NicaPlant® in plasma	AUC for multiple plasma samples	within 21 days post aneurysm rupture or within hospitalisation if shorter
Other	Nicardipine levels in cerebrospinal fluid (CSF) (only in patients provided with an external ventricular drain (EVD) at time of CSF removal for medical reasons)	Average concentration (Cav) for single CSF samples if sufficient CSF data is obtained.	within 21 days post aneurysm rupture or within hospitalisation if shorter
Other	Length of hospital stay	ANOVA	week 52 ± 2 after aneurysm rupture
Other	Modified Rankin Scale	Cochran-Mantel-Haenzel (CMH) test (with modified ridits); minimum value: 0, maximum value: 6, higher scores mean a worse outcome	week 12 ± 1 after aneurysm rupture
Other	Modified Rankin Scale	Cochran-Mantel-Haenzel (CMH) test (with modified ridits); minimum value: 0, maximum value: 6, higher scores mean a worse outcome	week 52 ± 2 after aneurysm rupture
Other	Glasgow Outcome Scale Extended	Cochran-Mantel-Haenzel (CMH) test (with modified ridits); minimum value: 1, maximum value: 8, higher scores mean a better outcome	week 12 ± 1 after aneurysm rupture
Other	Glasgow Outcome Scale Extended	Cochran-Mantel-Haenzel (CMH) test (with modified ridits); minimum value: 1, maximum value: 8, higher scores mean a better outcome	week 52 ± 2 after aneurysm rupture
Other	Montreal Cognitive Assessment	ANOVA; minimum value: 0, maximum value: 30, higher scores mean a better outcome	week 12 ± 1 after aneurysm rupture
Other	Montreal Cognitive Assessment	ANOVA; minimum value: 0, maximum value: 30, higher scores mean a better outcome	week 52 ± 2 after aneurysm rupture
Other	EQ-5D-5L	ANOVA	week 12 ± 1 after aneurysm rupture
Other	EQ-5D-5L	ANOVA	week 52 ± 2 after aneurysm rupture
Other	SF36	ANOVA	week 12 ± 1 after aneurysm rupture
Other	SF36	ANOVA	week 52 ± 2 after aneurysm rupture
Primary	Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography	Fishers Exact test	day 8 ± 1 after aneurysm rupture
Primary	Safety by adverse event recording	Descriptive summary	trough study completion, an average of 2 years
Secondary	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