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

Primary Purpose

Aneurysmal Subarachnoid Hemorrhage

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nicardipine
Standard of care
Sponsored by
BIT Pharma GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aneurysmal Subarachnoid Hemorrhage focused on measuring NicaPlant, Nicardipine

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie
  • Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie
  • Medizinische Universität Wien, Universitätsklinik für Neurochirurgie
  • Charité Universitätsmedizin Berlin, Klinik für Neurochirurgie mit Arbeitsbereich pädiatrische Neurochirurgie
  • Universitätsklinikum Göttingen, Neurochirurgische Klinik
  • Klinikum Rechts der Isar, Neurochirurgische Klinik und Poliklinik

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

NicaPlant®

Control

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography
Fishers Exact test
Safety by adverse event recording
Descriptive summary

Secondary Outcome Measures

Incidence of new cerebral infarcts on computer tomography (CT) of the brain versus post-intervention CT scan
Fishers exact test

Full Information

First Posted
January 23, 2020
Last Updated
July 11, 2023
Sponsor
BIT Pharma GmbH
Collaborators
NeuroScios GmbH, Data Magik Limited, Pharm-Analyt Labor GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT04269408
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 5, 2020 (Actual)
Primary Completion Date
May 12, 2022 (Actual)
Study Completion Date
January 23, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BIT Pharma GmbH
Collaborators
NeuroScios GmbH, Data Magik Limited, Pharm-Analyt Labor GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aneurysmal Subarachnoid Hemorrhage
Keywords
NicaPlant, Nicardipine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NicaPlant®
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
Other
Arm Description
Standard of care for aneurysmal subarachnoid haemorrhage patients according to the treatment guidelines.
Intervention Type
Drug
Intervention Name(s)
Nicardipine
Other Intervention Name(s)
NicaPlant®
Intervention Description
10 NicaPlant® implants releasing 4 mg nicardipine each.
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
Both arms receive the usual standard of care.
Primary Outcome Measure Information:
Title
Incidence of moderate to severe cerebral angiographic vasospasm assessed by digital subtraction angiography
Description
Fishers Exact test
Time Frame
day 8 ± 1 after aneurysm rupture
Title
Safety by adverse event recording
Description
Descriptive summary
Time Frame
trough study completion, an average of 2 years
Secondary Outcome Measure Information:
Title
Incidence of new cerebral infarcts on computer tomography (CT) of the brain versus post-intervention CT scan
Description
Fishers exact test
Time Frame
up to day 14 ± 1 after aneurysm rupture
Other Pre-specified Outcome Measures:
Title
Incidence of vasospasm-related morbidity/mortality
Description
Fishers exact test
Time Frame
within 21 days post aneurysm rupture
Title
Pharmacokinetic profile of NicaPlant® in plasma
Description
AUC for multiple plasma samples
Time Frame
within 21 days post aneurysm rupture or within hospitalisation if shorter
Title
Nicardipine levels in cerebrospinal fluid (CSF) (only in patients provided with an external ventricular drain (EVD) at time of CSF removal for medical reasons)
Description
Average concentration (Cav) for single CSF samples if sufficient CSF data is obtained.
Time Frame
within 21 days post aneurysm rupture or within hospitalisation if shorter
Title
Length of hospital stay
Description
ANOVA
Time Frame
week 52 ± 2 after aneurysm rupture
Title
Modified Rankin Scale
Description
Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 0, maximum value: 6, higher scores mean a worse outcome
Time Frame
week 12 ± 1 after aneurysm rupture
Title
Modified Rankin Scale
Description
Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 0, maximum value: 6, higher scores mean a worse outcome
Time Frame
week 52 ± 2 after aneurysm rupture
Title
Glasgow Outcome Scale Extended
Description
Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 1, maximum value: 8, higher scores mean a better outcome
Time Frame
week 12 ± 1 after aneurysm rupture
Title
Glasgow Outcome Scale Extended
Description
Cochran-Mantel-Haenzel (CMH) test (with modified ridits) minimum value: 1, maximum value: 8, higher scores mean a better outcome
Time Frame
week 52 ± 2 after aneurysm rupture
Title
Montreal Cognitive Assessment
Description
ANOVA minimum value: 0, maximum value: 30, higher scores mean a better outcome
Time Frame
week 12 ± 1 after aneurysm rupture
Title
Montreal Cognitive Assessment
Description
ANOVA minimum value: 0, maximum value: 30, higher scores mean a better outcome
Time Frame
week 52 ± 2 after aneurysm rupture
Title
EQ-5D-5L
Description
ANOVA
Time Frame
week 12 ± 1 after aneurysm rupture
Title
EQ-5D-5L
Description
ANOVA
Time Frame
week 52 ± 2 after aneurysm rupture
Title
SF36
Description
ANOVA
Time Frame
week 12 ± 1 after aneurysm rupture
Title
SF36
Description
ANOVA
Time Frame
week 52 ± 2 after aneurysm rupture

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudius Thomé, Prof.Dr.
Organizational Affiliation
Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsklinik Innsbruck, Universitätsklinik für Neurochirurgie
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Kepler Universitätsklinikum, Universitätsklinik für Neurochirurgie
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Medizinische Universität Wien, Universitätsklinik für Neurochirurgie
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Charité Universitätsmedizin Berlin, Klinik für Neurochirurgie mit Arbeitsbereich pädiatrische Neurochirurgie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Göttingen, Neurochirurgische Klinik
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Klinikum Rechts der Isar, Neurochirurgische Klinik und Poliklinik
City
Munich
ZIP/Postal Code
81675
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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