Clinical trial NCT01996436: The Intra-arterial Vasospasm Trial
Official title: The Intra-arterial Vasospasm Trial - A Multi-center Randomized Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cerebral Vasospasm
Keywords: cerebral vasospasm
aneurysmal subarachnoid hemorrhage
intra arterial drug treatment for cerebral vasospasm
nicardipine milrinone nitroglycerin verapamil
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Yale University
name: Thomas Jefferson University
name: University of Illinois at Chicago
name: Wake Forest University Health Sciences
name: Temple University
name: Geisinger Clinic
name: Northwell Health
name: University of Michigan
name: Lenox Hill Hospital
name: Weatherhead Foundation
name: University of California, Irvine
First posted: 2013-11-27
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The primary objective of the study is to determine the optimal intra-arterial drug treatment regimen for arterial lumen restoration post cerebral vasospasm following aneurysmal subarachnoid hemorrhage. The secondary objective is to evaluate clinical outcome at 90 days post discharge following optimal intra-arterial drug treatment for cerebral vasospasm.

We hypothesize that Intra-arterial (IA) infusion of a combination of multiple vasodilators is more efficacious than single agent treatment cerebral vasospasm therapy.

All procedures done as a part of this study are standard hospital care procedures done to treat cerebral vasospasm and all drugs to be used are FDA approved.

Detailed description: The primary objective of the study is to determine the optimal intra-arterial drug treatment regimen for arterial lumen restoration post cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

The secondary objective is to evaluate clinical outcome at 90 days post discharge following optimal intra-arterial drug treatment for cerebral vasospasm.

This study is a prospective multicenter randomized trial. The primary outcome measure is the Post infusion improvement ratio (PIIR) assessed 10 minutes after completion of the intra-arterial infusion. PIIR is a measure of arterial lumen diameter pre and post intra-arterial drug infusion in the presenting vasospasmic blood vessel.

Modified Rankin score (mRS) at 3 months post hospital discharge will be recorded as a secondary outcome to assess clinical outcome.

The interventions in this study are a part of routine standard of care (SOC) procedures for cerebral vasospasm treatment. Following surgical or endovascular intervention for aneurysmal Subarachnoid Hemorrhage (aSAH) if patients develop cerebral vasospasm refractory to maximal medical management, endovascular treatment by intra-arterial drug infusion of single drug agent or cocktail drug agents will be initiated.

Study participants will be randomly assigned to one of the three treatment groups where one single drug agent or cocktail drug agents will be intra-arterially administered. Pre \& post infusion vasospasmic vessel diameters will be compared. The change in diameter will be quantified based on the mean percentage change. Three months post hospital discharge, study participants will be followed up in clinic to evaluate clinical outcome.

The study will require 330 patients in total. The patient population will be hospitalized patients presenting with cerebral vasospasm post aneurysmal subarachnoid hemorrhage.

Subjects will be stratified by randomization into 3 treatment groups.

Eligibility criteria: Inclusion Criteria:

* Adult patient, age 18-80 years old, with ruptured aneurysm(s) who experience cerebral vasospasm post operatively within 3-21 days.
* Symptomatic vasospasm (clinical or TCD)
* For centers that perform a routine day 7 angiogram post-aneurysm treatment - 50% or more stenosis seen on diagnostic angiogram for asymptomatic patients.

Exclusion Criteria:

* Inability to obtain consent from patient or patients kin
* Pregnant women
* less than 18 years of age of more than 80 years of age
* Hunt Hess Grade 5 SAH
* Intra-arterial drug treatment in all 3 arterial territories

Primary outcomes:
measure: Post Infusion Improvement Ratio (PIIR)
timeFrame: pre pharmacological angioplasty blood vessel diameter - 0 min, post pharmacological angioplasty blood vessel diameter- 10 min after infusion
Secondary outcomes:
measure: Disability or Dependence in Daily Activities as Assessed by the Modified Rankin Score
timeFrame: 3 months post discharge from hospital
Other outcomes:
measure: Intra-cranial Pressure
timeFrame: 1 day prior to procedure & 1 day after the procedure
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Medical School at Houston
state: Texas
Study officials:
affiliation: University of Texas Medical School at Houston
name: Peng R Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UConn Health
name: Ketan R Bulsara, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Biller J, Godersky JC, Adams HP Jr. Management of aneurysmal subarachnoid hemorrhage. Stroke. 1988 Oct;19(10):1300-5. doi: 10.1161/01.str.19.10.1300. No abstract available.
citation: Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke. 1985 Jul-Aug;16(4):562-72. doi: 10.1161/01.str.16.4.562.
citation: Keuskamp J, Murali R, Chao KH. High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2008 Mar;108(3):458-63. doi: 10.3171/JNS/2008/108/3/0458.
citation: Linfante I, Delgado-Mederos R, Andreone V, Gounis M, Hendricks L, Wakhloo AK. Angiographic and hemodynamic effect of high concentration of intra-arterial nicardipine in cerebral vasospasm. Neurosurgery. 2008 Dec;63(6):1080-6; discussion 1086-7. doi: 10.1227/01.NEU.0000327698.66596.35.
citation: Badjatia N, Topcuoglu MA, Pryor JC, Rabinov JD, Ogilvy CS, Carter BS, Rordorf GA. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol. 2004 May;25(5):819-26.
citation: Pierot L, Aggour M, Moret J. Vasospasm after aneurysmal subarachnoid hemorrhage: recent advances in endovascular management. Curr Opin Crit Care. 2010 Apr;16(2):110-6. doi: 10.1097/MCC.0b013e3283372ef2.
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.