Endovascular treatment of cerebral vasospasm with milrinone and nimodipine

ISRCTN	ISRCTN36126862
DOI	https://doi.org/10.1186/ISRCTN36126862
Protocol serial number	4.1
Sponsor	Cerebrovascular Research Group Vienna
Funder	Investigator initiated and funded

Submission date: 31/10/2018
Registration date: 21/11/2018
Last edited: 16/06/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
More than 800 people every year in Austria suffer from severe brain bleeding because of ruptured aneurysms. An aneurysm is a balloon-shaped bulging of an arterial vessel within the head. Up to 4% of the population carry an aneurysm, but not all of them rupture. After bleeding from a ruptured aneurysm, severe and potentially lethal complications may follow. One of this is the spastic narrowing of the brain vessels, which is where the blood vessels in the brain can suddenly constrict, leading to reduced blood supply of the brain. This is called a cerebral vasospasm. It leads to a high number of deaths and in survivors, leads to an intensive need for help in daily activities. Currently, there is no specific treatment for cerebral vasospasm. This study aims to look at the effectiveness of a new drug combination (milrinone and nimodipine) for cerebral vasospasm.

Who can participate?
Adults who have had cerebral vasospasm after an ruptured aneurysm and are being treated in Krankenanstalt Rudolfstiftung in Vienna, Austria

What does the study involve?
Participants will be given 2 mg nimodipine for 20 minutes, followed by 5 mg milrinone given over 30 minutes. Participants will stay in intensive care for at least 21 days and will be followed up within at least 6 weeks after discharge.

What are the possible benefits and risks of participating?
There are no known benefits or risks to participants taking part in this study. The only known side effect of the drugs used is low blood pressure; however, this side effect is not seen in the application of drugs used in this study.

Where is the study run from?
Krankenanstalt Rudolfstiftung, Vienna (Austria)

When is the study starting and how long is it expected to run for?
June 2012 to June 2017

Who is funding the study?
Krankenanstalt Rudolfstiftung (Austria)

Who is the main contact?
Dr. Bernhard Wambacher
bernhard.wambacher@wienkav.at

Contact information

Dr Bernhard Wambacher
Scientific

Juchgasse 25/NChir.
Vienna
1030
Austria

Study information

Primary study design	Interventional
Study design	Interventional prospective single center non-randomised study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe cerebral vasospasm
Study objectives	Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe vasospasm improves neurological outcome and reduces mortality
Ethics approval(s)	Local Ethics Committee of the City of Vienna (Ethikkommission der Stadt Wien), 12/02/2018, EK 16-227-VK-NIS
Health condition(s) or problem(s) studied	Severe cerebral vasospasm
Intervention	All patients received endovascular therapy with 2 mg nimodipine infused over 20 minutes, followed by 5 mg milrinone infused over 30 minutes into the symptomatic vessels using an angiography catheter positioned extracranially/intra-arterially. All patients were monitored in the intensive care department or an intermediate care set-up for the period they were in a critical condition, but at least up to day 21 after initial bleeding. A routine clinical follow-up was completed within 6 weeks after discharge.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Nimodipine Milrinone
Primary outcome measure(s)	Clinical outcome, assessed at the baseline, on the day of discharge and at least 6 weeks after, using the following: 1. Glasgow Outcome Score (GOS) 2. Modified Ranking Scale (mRS)
Key secondary outcome measure(s)	The following are assessed at the baseline, on the day of discharge and after 6 weeks: 1. Vessel diameter, assessed using the Centricity Universal Viewer through digital subtraction of the angiogram pre- and post-intervention 2. Transcranial Doppler (TCD) values, assessed using a standard transcranial Doppler sonography set
Completion date	30/06/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	85 Years
Sex	All
Target sample size at registration	38
Total final enrolment	38
Key inclusion criteria	1. Aneurysmal subarachnoid haemorrhage 2. Consecutive cerebral vasospasm 3. Treated in Krankenanstalt Rudolfstiftung during the observational period 4. Aged 18-85 years
Key exclusion criteria	Not meeting the participant inclusion criteria
Date of first enrolment	01/01/2013
Date of final enrolment	01/04/2016

Locations

Countries of recruitment

Austria

Study participating centre

Krankenanstalt Rudolfstiftung

Juchgasse 25, 1030
Vienna
1030
Austria

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available from 01/12/2019. Requests via email from Bernhard Wambacher (bernhard.wambacher@wienkav.at).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/05/2025	16/06/2025	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

16/06/2025: Publication reference and total final enrolment added.
23/11/2018: Internal review.