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

Primary Purpose

Cerebral Vasospasm

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Milrinone
Placebo
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebral Vasospasm focused on measuring Subarachnoid Hemorrhage, Cerebral Vasospasm, Milrinone, Hyperdynamic Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Indiana University Heath Methodist Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Milrinone

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
March 15, 2016
Last Updated
June 12, 2019
Sponsor
Indiana University
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1. Study Identification

Unique Protocol Identification Number
NCT02712788
Brief Title
Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
Official Title
Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Terminated
Why Stopped
Completion not feasible due to lack of eligible subjects.
Study Start Date
April 18, 2016 (Actual)
Primary Completion Date
October 24, 2017 (Actual)
Study Completion Date
May 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Vasospasm
Keywords
Subarachnoid Hemorrhage, Cerebral Vasospasm, Milrinone, Hyperdynamic Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Milrinone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Milrinone
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Modified Rankin Scale (mRS) at 6 Months
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
mRS at 12 Months
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Shapiro, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Heath Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24313610
Citation
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.
Results Reference
background
PubMed Identifier
21773873
Citation
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.
Results Reference
background
PubMed Identifier
18239182
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.
Results Reference
background
PubMed Identifier
22528278
Citation
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.
Results Reference
background
PubMed Identifier
20023546
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.
Results Reference
background

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

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