Subarachnoid Aneurysm HemorrhageASH-IINCT07065903
Nimodipine Variability in SAH
An observational study of Subarachnoid Aneurysm Hemorrhage and Subarachnoid Hemorrhage, Aneurysmal, run by University of Alberta at 3 sites in 2 countries.
Trial summary
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological illness: it is bleeding in the brain after a bulging blood vessel (a brain aneurysm) ruptures. Although SAH accounts for only 5% of all strokes, it often happens in middle age and it puts a significant burden on many patients during their most… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Subarachnoid Aneurysm Hemorrhage, Subarachnoid Hemorrhage, Aneurysmal
- How many people
- 500 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 13 May 2024to Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients admitted for SAH to any of the participating centres.
Who may be able to join
- Age 18-85 years
- Diagnosis of aneurysmal SAH
- Provision of informed consent
- Treated with nimodipine
- Presence of intravascular catheter at the time of sampling
Who cannot join
- Anticipated hospital length of stay <48 hours
- Non-aneurysmal SAH
- Not treated with nimodipine
- Incarceration
- Delayed presentation to the hospital (>96 h from SAH onset)
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Canada2 sites, 2 recruiting
- Recruiting
University of Alberta Hospital
Edmonton, Alberta, T6G 2X8
Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS, 780-492-5364, smahmoud@ualberta.ca
Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS
- Recruiting
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Victoria McCredie, MBChB PhD FRCP(C) FRCP(UK), 416-302-1959, Victoria.McCredie@uhn.ca
United States1 site, 1 recruiting
- Recruiting
VCU Medical Center
Richmond, Virginia, 23219
Gretchen M Brophy, PharmD, BCPS, FCCP, FNCS, MCCM, 804-828-1201, gbrophy@vcu.edu
About this study
Official title: Nimodipine Systemic Exposure and Outcomes Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Multi-centre Observational Study (ASH-II Study)
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological illness: it is bleeding in the brain after a bulging blood vessel (a brain aneurysm) ruptures. Although SAH accounts for only 5% of all strokes, it often happens in middle age and it puts a significant burden on many patients during their most productive years. Complications following SAH are common, and they can cause major long-term disability. Only one medication - nimodipine - has been proven to benefit the health and wellbeing of these patients. All SAH patients should receive nimodipine for 21 days at a fixed dose. However, our early work suggested that all patients are not getting equal amounts of nimodipine into their blood. In addition, the two different forms (structural mirror images) of nimodipine might have different effects. Reduced amounts of nimodipine in the blood may lessen its benefit and contribute to worsening health and wellbeing of SAH patients.
The overall goal of this research is to see what happens with different nimodipine doses and to confirm whether the two forms of nimodipine have different effects. The investigators will conduct a multi-centre study in adult patients admitted for SAH in Canada and the USA. The investigators will collect blood samples to determine the amount of each type of nimodipine in each participant's body, and then will check to see how each participant is doing at 90 days following SAH. They will also check other factors affecting nimodipine levels, so that they can in the future suggest dose recommendations that are actually tailored to each patient.
Read the detailed description
Background and Importance:
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological illness characterized by the extravasation of blood into the subarachnoid space secondary to a ruptured brain aneurysm. Although SAH accounts for only 5% of all strokes, it often places a significant burden on the most productive years of a patient's life because of the relatively young average age at onset. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH and are significant contributors to disability in those surviving the initial bleed. Several agents have been tested to target vasospasm and DCI, but nimodipine was the only drug therapy that was shown to significantly improve neurological outcomes, and current guidelines recommend that all patients receive fixed-dose racemic nimodipine for 21 days following ictus. However, the pilot data suggested significant variability of nimodipine concentrations in the plasma, but it was not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening patient outcomes. Furthermore, the investigators' pilot data suggested that the two enantiomers of nimodipine might have differential effects, but it was not clear if one enantiomer is preferred over the other.
The overall goal of this research is to characterize the predictors and the clinical consequences of altered exposure to nimodipine enantiomers in SAH patients.
Research Aims:
- To determine the associations between systemic exposure to the two nimodipine enantiomers and the primary and secondary outcomes in SAH patients.
- To determine whether nimodipine enantiomers differ in their effects on safety in SAH patients.
- To determine the population pharmacokinetics of nimodipine enantiomers and to develop individualized dosing recommendations in SAH populations.
Approach:
This study is for a multi-centre prospective study in adult patients admitted to the hospital for SAH. Participants will have blood samples collected for the determination of plasma concentrations of nimodipine enantiomers. Participant data will be collected prospectively, and the primary outcome will be their modified Rankin Scale (mRS) score at 90 days following SAH onset. The mRS is a functional outcome scale commonly used SAH studies. Regression modeling will be used to determine if systemic exposures to nimodipine enantiomers (quantified as the area under the concentration-time curves) are independent predictors of mRS outcomes. Predictors of exposure to nimodipine enantiomers will also be determined using population pharmacokinetics, and individualized dosage regimens will be recommended.
- Keywords
- nimodipine, subarachnoid hemorrhage, pharmacokinetics
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Aneurysmal subarachnoid hemorrhage (SAH) Patients | Adult patients admitted for aneurysmal SAH to any of the participating centres, who consent to participate in the study and meet the inclusion and exclusion criteria. |
What is being measured
The primary outcome is the main question the study is designed to answer.
modified Rankin Scale (mRS) score
The mRS is a measure of disability ranging from 0 (no symptoms) to 6 (death) and is the recommended functional outcome scale in studies involving SAH patients.
Measured: 90 days from hospital admission
Secondary outcomes (2)
Delayed Cerebral Ischemia (DCI)
DCI is defined as "the occurrence of focal neurological impairment or a decrease of at least 2 points on the GCS. Such changes are not apparent immediately after aneurysm occlusion and cannot be attributed to other causes"
Measured: 21 days from hospital admission
Vasospasm
Vasospasm is defined as the presence of angiographic evidence of cerebral arterial narrowing
Measured: 21 days from hospital admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2025
- Study start13 May 2024
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid Aneurysm HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Alberta Health services, Foothills Medical Centre, Montreal Neurological Institute and Hospital, University Health Network, Toronto, Virginia Commonwealth University
- Responsible party
- Principal investigator, Sherif Mahmoud, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07065903
- Sponsor's protocol ID
- Pro00085618
- Acronym
- ASH-II
- Status last verified
- Feb 2026
- First submitted
- 2 Jul 2025
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared in accordance with maintaining patient confidentiality.
Publications
Mahmoud SH, Hefny F, Isse FA, Farooq S, Ling S, O'Kelly C, Kutsogiannis DJ. Nimodipine systemic exposure and outcomes following aneurysmal subarachnoid hemorrhage: a pilot prospective observational study (ASH-1 study). Front Neurol. 2024 Jan 5;14:1233267. doi: 10.3389/fneur.2023.1233267. eCollection 2023.
PubMed 38249736Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.
PubMed 20798370Mahmoud SH, Ji X, Isse FA. Nimodipine Pharmacokinetic Variability in Various Patient Populations. Drugs R D. 2020 Dec;20(4):307-318. doi: 10.1007/s40268-020-00322-3.
PubMed 32902829
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nimodipine Systemic Exposure and Outcomes Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Multi-centre Observational Study (ASH-II Study)
- ClinicalTrials.gov ID
- NCT07065903
- Acronym / sponsor ID
- ASH-II / Pro00085618
- Keywords
- nimodipine, subarachnoid hemorrhage, pharmacokinetics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Alberta Health services, Foothills Medical Centre, Montreal Neurological Institute and Hospital, University Health Network, Toronto, Virginia Commonwealth University
- Study start
- 13 May 2024 (actual)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 15 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological illness: it is bleeding in the brain after a bulging blood vessel (a brain aneurysm) ruptures. Although SAH accounts for only 5% of all strokes, it often happens in middle age and it puts a significant burden on many patients during their most productive years. Complications following SAH are common, and they can cause major long-term disability. Only one medication - nimodipine - has been proven to benefit the health and wellbeing of these patients. All SAH patients should receive nimodipine for 21 days at a fixed dose. However, our early work suggested that all patients are not getting equal amounts of nimodipine into their blood. In addition, the two different forms (structural mirror images) of nimodipine might have different effects. Reduced amounts of nimodipine in the blood may lessen its benefit and contribute to worsening health and wellbeing of SAH patients.
The overall goal of this research is to see what happens with different nimodipine doses and to confirm whether the two forms of nimodipine have different effects. The investigators will conduct a multi-centre study in adult patients admitted for SAH in Canada and the USA. The investigators will collect blood samples to determine the amount of each type of nimodipine in each participant's body, and then will check to see how each participant is doing at 90 days following SAH. They will also check other factors affecting nimodipine levels, so that they can in the future suggest dose recommendations that are actually tailored to each patient.
Detailed description
Background and Importance:
Aneurysmal subarachnoid hemorrhage (SAH) is a life-threatening neurological illness characterized by the extravasation of blood into the subarachnoid space secondary to a ruptured brain aneurysm. Although SAH accounts for only 5% of all strokes, it often places a significant burden on the most productive years of a patient's life because of the relatively young average age at onset. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH and are significant contributors to disability in those surviving the initial bleed. Several agents have been tested to target vasospasm and DCI, but nimodipine was the only drug therapy that was shown to significantly improve neurological outcomes, and current guidelines recommend that all patients receive fixed-dose racemic nimodipine for 21 days following ictus. However, the pilot data suggested significant variability of nimodipine concentrations in the plasma, but it was not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening patient outcomes. Furthermore, the investigators' pilot data suggested that the two enantiomers of nimodipine might have differential effects, but it was not clear if one enantiomer is preferred over the other.
The overall goal of this research is to characterize the predictors and the clinical consequences of altered exposure to nimodipine enantiomers in SAH patients.
Research Aims:
- To determine the associations between systemic exposure to the two nimodipine enantiomers and the primary and secondary outcomes in SAH patients.
- To determine whether nimodipine enantiomers differ in their effects on safety in SAH patients.
- To determine the population pharmacokinetics of nimodipine enantiomers and to develop individualized dosing recommendations in SAH populations.
Approach:
This study is for a multi-centre prospective study in adult patients admitted to the hospital for SAH. Participants will have blood samples collected for the determination of plasma concentrations of nimodipine enantiomers. Participant data will be collected prospectively, and the primary outcome will be their modified Rankin Scale (mRS) score at 90 days following SAH onset. The mRS is a functional outcome scale commonly used SAH studies. Regression modeling will be used to determine if systemic exposures to nimodipine enantiomers (quantified as the area under the concentration-time curves) are independent predictors of mRS outcomes. Predictors of exposure to nimodipine enantiomers will also be determined using population pharmacokinetics, and individualized dosage regimens will be recommended.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aneurysmal subarachnoid hemorrhage (SAH) Patients | – | –Adult patients admitted for aneurysmal SAH to any of the participating centres, who consent to participate in the study and meet the inclusion and exclusion criteria. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients admitted for SAH to any of the participating centres.
Key inclusion criteria (5 listed)
- Age 18-85 years
- Diagnosis of aneurysmal SAH
- Provision of informed consent
- Treated with nimodipine
- Presence of intravascular catheter at the time of sampling
Key exclusion criteria (5 listed)
- Anticipated hospital length of stay <48 hours
- Non-aneurysmal SAH
- Not treated with nimodipine
- Incarceration
- Delayed presentation to the hospital (>96 h from SAH onset)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
modified Rankin Scale (mRS) score
Time frame: 90 days from hospital admission
The mRS is a measure of disability ranging from 0 (no symptoms) to 6 (death) and is the recommended functional outcome scale in studies involving SAH patients.
2 secondary outcomes
Delayed Cerebral Ischemia (DCI)
Time frame: 21 days from hospital admission
Vasospasm
Time frame: 21 days from hospital admission
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Background: PubMed 38249736Mahmoud SH, Hefny F, Isse FA, Farooq S, Ling S, O'Kelly C, Kutsogiannis DJ. Nimodipine systemic exposure and outcomes following aneurysmal subarachnoid hemorrhage: a pilot prospective observational study (ASH-1 study). Front Neurol. 2024 Jan 5;14:1233267. doi: 10.3389/fneur.2023.1233267. eCollection 2023.
- Background: PubMed 20798370Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(10):2391-5. doi: 10.1161/STROKEAHA.110.589275. Epub 2010 Aug 26.
- Background: PubMed 32902829Mahmoud SH, Ji X, Isse FA. Nimodipine Pharmacokinetic Variability in Various Patient Populations. Drugs R D. 2020 Dec;20(4):307-318. doi: 10.1007/s40268-020-00322-3.
- Neuro-CPK Laboratory WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. IPD will not be shared in accordance with maintaining patient confidentiality.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subarachnoid Aneurysm Hemorrhage and Subarachnoid Hemorrhage, Aneurysmal, run by University of Alberta at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sherif H Mahmoud, BSc (Pharm), MSc, PhD, FNCS (780.492.5364, smahmoud@ualberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
modified Rankin Scale (mRS) score (time frame: 90 days from hospital admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07065903, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.