Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Cerebral Vasospasm Clinical Trial

Official title:

Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02712788
• Other study ID #: 1505714749
• Status: Terminated
• Phase: Phase 2
• Start date: April 18, 2016
• Est. completion date: May 3, 2018

Study information

• Verified date: June 2019
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the usefulness of adding Milrinone to the current standard treatment for cerebral vasospasm.

Description:

The goal of this study is to assess the efficacy of milrinone as an agent to treat cerebral vasospasm by adding it to standard therapy. This will take the form of a randomized, controlled trial in which patients will receive either standard hyperdynamic therapy or hyperdynamic therapy + milrinone. The hypothesis of this study is that good outcomes will be 25% more common in the experimental (milrinone) group than the control (standard therapy) group.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: May 3, 2018
• Est. primary completion date: October 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects = 18 years of age

• Aneurysmal subarachnoid hemorrhage, proven on CT angiogram or digital subtraction angiography

• Aneurysm treated, either by endovascular embolization or surgical clip ligation

• Evidence of increased velocities on transcranial dopplers (TCDs) and/or radiographic evidence of vasospasm as seen on angiogram

• Cerebral vasospasm as demonstrated by patient's clinical exam (new focal deficit or change in mental status not attributable to any other cause)

Exclusion Criteria:

• Recurrent subarachnoid hemorrhage

• Untreated ruptured aneurysm, for any reason

• Patients who die prior to treatment for aneurysm

• Patients who are not able to complete at least 6 months of follow-up

• Patients who are admitted already in vasospasm (i.e. a delayed admission)

• Creatinine clearance less than 20 ml/min

• Women with a positive pregnancy test or who are lactating

• Other comorbidity which may adversely affect patient outcome, at the discretion of the principal investigator

Related Conditions & MeSH terms

• Cerebral Vasospasm
• Hemorrhage
• Subarachnoid Hemorrhage
• Vasospasm, Intracranial

Intervention

Drug:
• Milrinone

• Placebo

Locations

Country	Name	City	State
United States	Indiana University Heath Methodist Hospital	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Abla AA, Wilson DA, Williamson RW, Nakaji P, McDougall CG, Zabramski JM, Albuquerque FC, Spetzler RF. The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial. J Neurosurg. 2014 Feb;120(2):391-7. doi: 10.3171/2013.10.JNS13419. Epub 2013 Dec 6. — View Citation

Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, Hänggi D, Hoh BL, Lanzino G, Le Roux P, Rabinstein A, Schmutzhard E, Stocchetti N, Suarez JI, Treggiari M, Tseng MY, Vergouwen MD, Wolf S, Zipfel G; Neurocritical Care Society. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care. 2011 Sep;15(2):211-40. doi: 10.1007/s12028-011-9605-9. Review. — View Citation

Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008 Mar;39(3):893-8. doi: 10.1161/STROKEAHA.107.492447. Epub 2008 Jan 31. — View Citation

Lannes M, Teitelbaum J, del Pilar Cortés M, Cardoso M, Angle M. Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol. Neurocrit Care. 2012 Jun;16(3):354-62. doi: 10.1007/s12028-012-9701-5. — View Citation

Nishiguchi M, Ono S, Iseda K, Manabe H, Hishikawa T, Date I. Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo: effectiveness of cisternal injection of milrinone. Neurosurgery. 2010 Jan;66(1):158-64; discussion 164. doi: 10.1227/01.NEU.0000363153.62579.FF. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale (mRS) at 6 Months	Reported as number for each subject and then will look statistically to see if there is a difference between the active arm and the placebo arm. The Modified Rankin scale is Scored as follows: 0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death. Higher scores indicate worse outcome.	6 months
Secondary	mRS at 12 Months	Reported as number for each subject and then will look statistically to see if there is a difference between the active arm and the placebo arm. THe Modified Rankin Scale is Scored as follows: 0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death. Higher scores indicate worse outcome.	12 months