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

NCT04269408 | Completed Phase 2 DMC

• 2 other identifiers: BIT-0022017-005159-10
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 6

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).

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

NicaPlant; Nicardipine

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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

Other Outcomes (14)

• Incidence of vasospasm-related morbidity/mortality

  within 21 days post aneurysm rupture

• Pharmacokinetic profile of NicaPlant® in plasma

  within 21 days post aneurysm rupture or within hospitalisation if shorter

• 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

Study Arms (2)

NicaPlant®

EXPERIMENTAL

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; Other: Standard of care

Control

OTHER

Standard of care for aneurysmal subarachnoid haemorrhage patients according to the treatment guidelines.

Other: Standard of care

Interventions

Nicardipine DRUG

10 NicaPlant® implants releasing 4 mg nicardipine each.

Also known as: NicaPlant®

NicaPlant®

Standard of care OTHER

Both arms receive the usual standard of care.

Control; NicaPlant®

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BIT Pharma GmbH: lead
• NeuroScios GmbH: collaborator
• Data Magik Limited: collaborator
• Pharm-Analyt Labor GmbH: collaborator

Study Sites (6)

Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie

Innsbruck, 6020, Austria

Location

Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie

Linz, 4020, Austria

Location

Medizinische Universität Wien, Universitätsklinik für Neurochirurgie

Vienna, 1090, Austria

Location

Charité Universitätsmedizin Berlin, Klinik für Neurochirurgie mit Arbeitsbereich pädiatrische Neurochirurgie

Berlin, 10117, Germany

Location

Universitätsklinikum Göttingen, Neurochirurgische Klinik

Göttingen, 37075, Germany

Location

Klinikum Rechts der Isar, Neurochirurgische Klinik und Poliklinik

Munich, 81675, Germany

Location

Related Publications (1)

• Wessels L, Wolf S, Adage T, Breitenbach J, Thome C, Kerschbaumer J, Bendszus M, Gmeiner M, Gruber A, Mielke D, Rohde V, Wostrack M, Meyer B, Gempt J, Bavinzski G, Hirschmann D, Vajkoczy P, Hecht N. Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. JAMA Neurol. 2024 Oct 1;81(10):1060-1065. doi: 10.1001/jamaneurol.2024.2564.

  PMID: 39158893 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Nicardipine; Standard of Care

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Claudius Thomé, Prof.Dr.

  Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 13, 2020
• Study Start: April 5, 2020
• Primary Completion: May 12, 2022
• Study Completion: January 23, 2023
• Last Updated: July 12, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); AU (3)