NCT02712788

Brief Summary

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

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2016

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 15, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 18, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

April 18, 2016

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 24, 2017

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 3, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

July 2, 2019

Completed
Last Updated

July 2, 2019

Status Verified

June 1, 2019

Enrollment Period

1.5 years

First QC Date

March 15, 2016

Results QC Date

August 24, 2018

Last Update Submit

June 12, 2019

Conditions

Cerebral Vasospasm

Keywords

Subarachnoid HemorrhageCerebral VasospasmMilrinoneHyperdynamic Therapy

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • mRS at 12 Months

    12 months

Study Arms (2)

Milrinone

ACTIVE COMPARATOR

Milrinone will be administered intravenously at an initial rate of 0.75mCg/kg/min and titrated based on symptoms in addition to hyperdynamic therapy and angiographic therapy as indicated per institutional protocol.

Drug: Milrinone

Placebo

PLACEBO COMPARATOR

Placebo (Normal Saline) will be administered intravenously and titrated based on symptoms in addition to hyperdynamic therapy and angiographic therapy as indicated per institutional protocol.

Drug: Placebo

Interventions

MilrinoneDRUG
Milrinone
PlaceboDRUG
Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Indiana University Heath Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Related 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.

    PMID: 24313610BACKGROUND

  • Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, Hanggi 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.

    PMID: 21773873BACKGROUND

  • 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.

    PMID: 18239182BACKGROUND

  • Lannes M, Teitelbaum J, del Pilar Cortes 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.

    PMID: 22528278BACKGROUND

  • 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.

    PMID: 20023546BACKGROUND

MeSH Terms

Conditions

Vasospasm, IntracranialSubarachnoid Hemorrhage

Interventions

Milrinone

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesIntracranial HemorrhagesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AmrinoneAminopyridinesAminesOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Heather Cero, RN - research cooordinator
Organization
Indiana University
hcero@iupui.edu
317-396-1398

Study Officials

  • Scott Shapiro, MD

    Indiana University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, Professor of Neurological Surgery

Study Record Dates

First Submitted

March 15, 2016

First Posted

March 18, 2016

Study Start

April 18, 2016

Primary Completion

October 24, 2017

Study Completion

May 3, 2018

Last Updated

July 2, 2019

Results First Posted

July 2, 2019

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will not share

Locations

US(1)