NIMODIPINE for Aneurysmal subarachnoid hemorrhage

Inclusion criteria

• {"criterion_text":"- 1. Male or female patients aged ≥18 years and <80 years"}
• {"criterion_text":"- 2. Modified Fisher grade 3 or 42"}
• {"criterion_text":"- 3. Cisternal/Ventricular blood amount according to Hijdra Score ≥ 203"}
• {"criterion_text":"- 4. Admission WFNS grade ≥ 3 (if grade 5 only with fixed dilated pupil due to raised ICP for less than 45 minutes) XML File Identifier: 1QQAfUUsgOy4U/EmSL6g0y1IS/g= Page 18/31"}
• {"criterion_text":"- 5. External ventricular drain (EVD) in situ or indication for placement of EVD"}
• {"criterion_text":"- 6. Disease duration ≤96 hours before randomization"}
• {"criterion_text":"- 7. Written informed consent, either by patient or by patient's legally authorized representative"}
• {"criterion_text":"- 8. Cerebral aneurysm as definitive source of subarachnoid hemorrhage"}
• {"criterion_text":"- 9. Patients in whom the cerebral aneurysm has been safely treated via open surgical or endovascular technique."}

Exclusion criteria

• {"criterion_text":"- 1. Pregnancy"}
• {"criterion_text":"- 2. Surgical contraindications according to the opinion of the investigator"}
• {"criterion_text":"- 3. Inability to administer study medication (known allergy to urokinase or nimodipine)"}
• {"criterion_text":"- 4. Presence of a severe illness prior to aSAH (e.g. progressive cancer, terminal organ failure, severe neurological disorder, life expectancy < 1 year)"}
• {"criterion_text":"- 5. Known and persistent abuse of medication or drugs"}
• {"criterion_text":"- 6. Presence of severe cerebral infarction related to the aSAH or medical procedures prior to randomization"}
• {"criterion_text":"- 7. Presence of intracerebral hematoma that is ≥ 30ml (assessed using the AxBxC/2 method)5 or in eloquent location prior to randomization"}
• {"criterion_text":"- 8. Presence of a condition or abnormality that in the opinion of the Investigator would compromise safety of the patient"}
• {"criterion_text":"- 9. Known severe complications during aneurysm securing (e.g. dissections of blood vessels, vessel occlusions, re-hemorrhage)"}
• {"criterion_text":"- 10. Clinical signs of brain stem / midbrain compression (dilated pupil not reacting to light) persisting for more than 45 minutes at any time between aSAH onset and randomization"}
• {"criterion_text":"- 11. Persons who are in a relationship of dependence/employment with the sponsor or the investigator"}
• {"criterion_text":"- 12. For MRI follow-up: cardiac pacemaker and/or cardiac defibrillator. Stent implantation within the last 6 weeks prior to MRI, claustrophobia"}

Primary endpoints

• {"endpoint_text":"- Neurological outcome: Proportion of subjects with a favorable outcome measured on the modified Rankin Scale (mRS) at 6months after aSAH, assessed by an independent physician. mRS will be analyzed in a dichotomized fashion: favorable, defined as: mRS 0-3 (independent) vs. unfavorable, defined as: mRS 4-6 (dependent/dead)","definition_or_measurement_approach":"Assessed by an independent physician at 6 months after aSAH using the modified Rankin Scale (mRS); analyzed dichotomously with favorable = mRS 0-3 and unfavorable = mRS 4-6."}

Secondary endpoints

• {"endpoint_text":"- 1. mRS at 12 months after aSAH","definition_or_measurement_approach":"Modified Rankin Scale at 12 months after aSAH."}
• {"endpoint_text":"- 2. Neuropsychological outcome a)Neuropsychological outcome b) Health-related quality of life (SF-36) at 6 months c) Fatigue, anxiety and depressive symptoms (Frontal Systems Behavior Scale, Multidimensional Assessment of Fatigue, Hospital Anxiety and Depression Scale), Post-traumatic stress disorder (Impact of Event Scale – R) at 6 months d) Return-to-work parameters at 6 and 12 months","definition_or_measurement_approach":"Cognitive and neuropsychological assessments including SF-36, Frontal Systems Behavior Scale, Multidimensional Assessment of Fatigue, Hospital Anxiety and Depression Scale, Impact of Event Scale – R; return-to-work assessed at 6 and 12 months."}
• {"endpoint_text":"- 3. Rate and severity of delayed cerebral infarction (DCI) according to the Vergouwen criteria","definition_or_measurement_approach":"Rate and severity assessed per Vergouwen criteria for DCI."}
• {"endpoint_text":"- 4. Rate of delayed ischemic neurological deficit (DIND), defined as clinical deterioration caused by delayed cerebral ischemia (i.e. a new focal neurological deficit or decline on the Glasgow Coma Scale of 1 point not attributable to other causes) on days 3 – 21. (Note: The date of aSAH occurrence is defined as day 0.)","definition_or_measurement_approach":"DIND defined as new focal neurological deficit or GCS decline of ≥1 point between days 3–21 not attributable to other causes."}
• {"endpoint_text":"- 5. Delta mean flow velocities of both middle cerebral arteries – measured by transcranial Doppler-ultrasonography on days 3 – 15.","definition_or_measurement_approach":"Change in mean flow velocities of both middle cerebral arteries measured by transcranial Doppler on days 3–15."}
• {"endpoint_text":"- 6. NIHSS score at day 32 and at 6 months","definition_or_measurement_approach":"National Institutes of Health Stroke Scale measured at day 32 and 6 months."}
• {"endpoint_text":"- 7. Rates of shunt-dependent hydrocephalus at 6 months following aSAH","definition_or_measurement_approach":"Proportion of subjects requiring permanent CSF shunt at 6 months."}
• {"endpoint_text":"- 8. Rate of endovascular interventions for the treatment of cerebral vasospasm","definition_or_measurement_approach":"Proportion of subjects undergoing endovascular intervention for vasospasm."}
• {"endpoint_text":"- 9. Key parameters of endocrinological dysfunction","definition_or_measurement_approach":"Assessment of predefined endocrine dysfunction parameters (details per protocol)."}
• {"endpoint_text":"- 10. Morphological brain damage at 6 months after aSAH as assessed by MRI","definition_or_measurement_approach":"MRI-based assessment of morphological brain damage at 6 months."}
• {"endpoint_text":"- 11. Key markers of neuronal injury and systemic inflammation in patient blood","definition_or_measurement_approach":"Measurement of predefined blood biomarkers of neuronal injury and systemic inflammation."}
• {"endpoint_text":"- 12. electroencephalographic patterns as measured by continuous EEGmonitoring during intensive care period (exploratory endpoint)","definition_or_measurement_approach":"Continuous EEG monitoring during ICU stay; analysis of EEG patterns (exploratory)."}
• {"endpoint_text":"- 13. Safety of IT: (Serious) Adverse Events related to the IT","definition_or_measurement_approach":"Recording and reporting of (serious) adverse events related to the investigational treatment (IT)."}

Germany

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

184

Number Of Sites

1

Number Of Participants

54

Primary sponsor

Full Name

Medical Center - University Of Freiburg

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Else Kröner-Fresenius-Stiftung","duties_or_roles":"Source of monetary support","organisation_type":""}