Simvastatin For Intracerebral Hemorrhage Study

Study Objective: To analyze if statins are effective in ameliorating perihematomal edema evolution thereby reducing mortality and improving functional outcomes following spontaneous intracerebral hemorrhage (ICH).

Study Overview

• Status: Terminated
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Simvastatin 80 mg; Drug: Placebo

Detailed Description

Intracerebral hemorrhage (ICH) causes 10% to 15% of first-ever strokes, with a 30-day mortality rate of 35% to 52% with only 20% expected to be functionally independent at 6 months. No medical or surgical interventions have been found to alter the natural evolution of this disease. The high risk for mortality and poor outcomes seems to occur despite relatively small hematoma volumes and small amounts of neuronal tissue at risk for injury. The reasons for this observation remain unknown; however perihematomal edema formation and inflammation that follows ICH seems to play an important role.

The Simvastatin for Intracerebral Hemorrhage Study is a prospective double blinded placebo controlled randomized (1:1) clinical trial that compares outcomes in patients receiving generic simvastatin 80 mg for 14 days or until death or discharge with patients in the placebo group.

The hypothesis for our study is that statins ameliorate perihematomal edema evolution thereby reducing mortality and improving functional outcomes following Intracerebral Hemorrhage (ICH). This hypothesis in turn is based on animal data showing suppression of inflammatory reaction and improved neurological outcomes following administration of statins to rodents with experimental ICH, and on a retrospective review of patients admitted to The Johns Hopkins Hospital over the last 7 years with spontaneous ICH which showed significantly better outcomes (decreased 30 day mortality secondary to decreased perihematomal edema) in patients on statins at the time of admission.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with CT evidence of ICH admitted within 24 hours of onset of symptoms.

Exclusion Criteria:

• Age < 18 or > 85
• Admission Glasgow Coma Score (GCS) < 6
• ICH volume < 10 cc
• ICH secondary to trauma, aneurysm, Arterio-Venous Malformation (AVM), tumor or post surgical
• Multiple ICH
• Associated Subdural hematoma or significant Subarachnoid hemorrhage
• History of prior neurologic disease with modified Rankin Scale (mRS) > 1
• Hematoma evacuation, hemicraniectomy, clot lysis
• Myopathy
• Active Liver disease
• Pregnancy
• Statin allergy
• Patients on statins prior to admission
• Patients with an acute indication for statin therapy (Unstable angina)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I; Simvastatin Group	Drug: Simvastatin 80 mg; Patients in study arm 1 will receive simvastatin 80 mg once daily for 14 days or until death or discharge.
Placebo Comparator: II; Placebo Group	Drug: Placebo; Patients in study arm II will receive placebo once daily for 14 days or until death or discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perihematomal Edema	Solitary patient lost to follow up (out of state)	Days 7 and 14

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institutes of Health (NIH); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Neeraj S Naval, M.D., Johns Hopkins University

Publications and helpful links

General Publications

• Naval NS, Abdelhak TA, Zeballos P, Urrunaga N, Mirski MA, Carhuapoma JR. Prior statin use reduces mortality in intracerebral hemorrhage. Neurocrit Care. 2008;8(1):6-12. doi: 10.1007/s12028-007-0080-2.
• Naval NS, Abdelhak TA, Urrunaga N, Zeballos P, Mirski MA, Carhuapoma JR. An association of prior statin use with decreased perihematomal edema. Neurocrit Care. 2008;8(1):13-8. doi: 10.1007/s12028-007-0081-1.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 16, 2008
• First Posted (Estimate): July 18, 2008

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Edema; Statins; Hemorrhage; Intracerebral
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: NA_00016284; NIH UL1 RR 025005