NICARDIPINE Implant
(2024)Objective
To evaluate the safety and efficacy of localized nicardipine release implants for the prevention of moderate to severe angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).
Study Summary
Intervention
Intraoperative placement of 10 nicardipine implants (4 mg each) around the basal cerebral vasculature during microsurgical clipping of ruptured anterior circulation aneurysms, in addition to standard of care.
Inclusion Criteria
Patients with World Federation of Neurological Surgeons (WFNS) grade 3 or 4 aneurysmal subarachnoid hemorrhage from ruptured anterior circulation aneurysms requiring microsurgical clipping, enrolled within 48 hours of rupture.
Study Design
Arms: Nicardipine implant group (implants + standard care) vs. control group (standard care only).
Patients per Arm: Implant group: 21, Control group: 20
Outcome
Bottom Line
Intraoperative nicardipine release implants (10 implants, 4mg each) placed around basal cerebral vasculature during aneurysm clipping significantly reduced moderate-to-severe angiographic vasospasm from 58% to 20% (P=0.02) in WFNS grade 3-4 aSAH patients. Rescue therapy need reduced from 58% to 10% (P=0.002). Safety profile equivalent to standard care. Phase 2b trial, 41 patients, 6 centers in Germany/Austria.
Major Points
- Moderate-severe aVS reduced from 58% to 20% (P=0.02) — 38 percentage-point ARR.
- Rescue therapy (IA vasodilator/PTA/induced HTN): 58% vs 10% (P=0.002).
- Localized delivery: plasma nicardipine stayed below systemic active levels (max 1.27 ng/mL).
- New cerebral infarcts (DCI): 32% vs 10% (P=0.13, NS — underpowered).
- ICU stay trended shorter: 20.8 vs 30.2 days (P=0.06).
- 52-week favorable outcome: 84% vs 67% (P=0.27, NS — underpowered).
- Phase 2b, 41 patients, 6 academic centers (Germany/Austria). Single-masked.
- Only WFNS grade 3-4 with anterior circulation aneurysms requiring clipping.
- Funded by BIT Pharma (NicaPlant manufacturer). Phase 3 needed.
- Aneurysm location significantly imbalanced (P=0.01) — key confounder.
Study Design
- Study Type
- Phase 2b randomized clinical trial
- Randomization
- Yes
- Blinding
- Single-masked (surgeon unblinded, other clinical staff masked)
- Sample Size
- 41
- Follow-up
- 52 weeks
- Centers
- 6
- Countries
- Germany, Austria
Primary Outcome
Definition: Incidence of moderate-to-severe angiographic vasospasm (days 7–9)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 58% (11/19) | 20% (4/20) | - (Control: 34%-80%, Intervention: 6%-44%) | 0.02 |
Limitations & Criticisms
- Small sample size and phase 2b design limits generalizability
- Trial limited to patients undergoing surgical clipping (not endovascular group)
- Low ethnic diversity
- Not powered to detect mortality or long-term functional outcome differences
Citation
JAMA Neurol. 2024;81(10):1060-1065