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TerminatedNCT00774306Updated Dec 18, 2017Results posted

Antiepileptic Drugs and Vascular Risk Markers

An interventional study of phenytoin and valproate in Subarachnoid Hemorrhage, sponsored by Thomas Jefferson University. Terminated. Per ClinicalTrials.gov, last updated 2017-12-18.

Sponsored by Thomas Jefferson University · Not applicable, Interventional, and Treatment

Why this study was terminated
study no longer consistent with current clinical practice
Phase
Not applicable
Study type
Interventional
Enrollment
52
Allocation
Randomized
Sex
All
01

Study summary

The purpose of this study is to determine if certain seizure medications raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes.

Read the detailed description

There is some evidence that certain seizure medicines may raise levels of cholesterol and other blood components which could increase the risk of heart attacks and strokes, however, more research is needed. Individuals with acute subarachnoid hemorrhage traditionally are treated with seizure medicines, but it is not clear which one is best, or if any such medication is necessary at all.

This study is intended to find out if certain seizure medications raise levels of cholesterol and other blood components which could lead to an increased risk of heart attacks and strokes.

In this study, 200 people with acute subarachnoid hemorrhage will be randomized to treatment with one of three different seizure medicines-phenytoin, valproate, or levetiracetam-or to receive no seizure medication at all. In each participant, cholesterol and other blood markers that relate to heart attack and stroke risk will be measured shortly after hospital admission and again 8 weeks later. At the 8-week point most participants will have their seizure medication discontinued, and the same blood tests will be repeated.

Information from this study could lead to changes in how seizure medications are prescribed both in the subarachnoid hemorrhage population and in other people who are prone to seizures.

02

Conditions studied

  • Subarachnoid Hemorrhage

Keywords

  • vascular risk
  • lipid fractions
  • lipoprotein(a)
  • C-reactive protein
  • subarachnoid hemorrhage
  • antiepileptic drug
  • randomized
  • seizure
  • cholesterol
03

In context

Subarachnoid Hemorrhage

509 studies on the registry are indexed under Subarachnoid Hemorrhage; 124 are open to participants now.

This study's enrollment of 52 is close to the median of 52 across 263 interventional studies indexed under Subarachnoid Hemorrhage.

Browse Subarachnoid Hemorrhage studies →

Lead sponsor

Thomas Jefferson University is the lead sponsor of 384 studies on the registry; 71 are open to participants now.

Of its 44 completed or terminated interventional studies of FDA-regulated products, 20 (45%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Acute subarachnoid hemorrhage, Hunt-Hess Grades I-IV
  • Within 48 hours of admission

Exclusion criteria

Exclusion Criteria:

  • Grade V subarachnoid hemorrhage
  • Being treated with a lipid-lowering agent
  • Contraindication to phenytoin, valproate, or levetiracetam (e.g. history of allergy to one of these agents)
  • Contraindication to receiving no antiepileptic drug treatment (e.g. history of pre-existing epilepsy, seizure activity on admission EEG)
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
52 participants (actual)

Study arms

  • Active comparator
    1

    Participants randomized to Group 1 will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.

    Drug: phenytoin

  • Active comparator
    2

    Participants randomized to Group 2 will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses or in a once-daily extended release formulation.

    Drug: valproate

  • Active comparator
    3

    Participants randomized to Group 3 will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.

    Drug: levetiracetam

  • No intervention
    4

    Participants randomized to Group 4 will receive no drug intervention.

Interventions

  • Drugphenytoin

    Phenytoin is a anti-seizure medication. Participants will receive phenytoin (PHT) at 5 mg/kg/day in 2 divided doses.

    Also known as: Dilantin, Cerebyx (a phenytoin pro-drug)

  • Drugvalproate

    Valproate is an anti-seizure medication. Participants will receive valproate (VPA) at 15 mg/kg/day in 3 divided doses.

    Also known as: Depakote, Depacon

  • Druglevetiracetam

    Levetiracetam is an anti-seizure medication. Participants will receive levetiracetam (LEV) 1000-1500 mg/day in 2 divided doses.

    Also known as: Keppra

06

What researchers measure

Primary outcomes

  1. Change in Serum Cholesterol, Non-HDL Cholesterol, HDL Cholesterol, Lipoprotein(a), and C-reactive Protein From Baseline to Second Draw and Third Draw in Each of the 4 Study Arms

    Time frame: 8 weeks, 16 weeks

Secondary outcomes

  1. Incidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores)

    Time frame: 8 weeks, 16 weeks

07

Results

Posted Nov 25, 2014
Limitations and caveats
Study terminated due to 1) change in clinical practice; 2) inadequate recruitment and follow-up. Number of pts providing full data was \<15% of goal. Because of this, any analysis of data was considered futile, and no analyses were performed.

Participant flow

Participant flow — Overall Study
MilestonePhenytoinValproateLevetiracetamNo Anticonvulsant
Started245167
Completed6382
Not completed18285
Withdrew: Adverse event3000
Withdrew: Protocol violation2030
Withdrew: Withdrawal by subject6110
Withdrew: Lost to follow-up6045
Withdrew: Death1100

Outcome measures

PrimaryChange in Serum Cholesterol, Non-HDL Cholesterol, HDL Cholesterol, Lipoprotein(a), and C-reactive Protein From Baseline to Second Draw and Third Draw in Each of the 4 Study Arms
Time frame:
8 weeks, 16 weeks

No measurements were reported for this outcome.

SecondaryIncidence of Acute Seizures, Incidence of Late Seizures, Overall Neurologic Function (as Measured by Modified Rankin Scale Scores)
Time frame:
8 weeks, 16 weeks

Results for this outcome have not been posted.

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Phenytoin—4/24 (16.7%)0/24 (0%)
Valproate—1/5 (20%)1/5 (20%)
Levetiracetam—4/16 (25%)0/16 (0%)
No Anticonvulsant—3/7 (42.9%)0/7 (0%)
Most frequent serious events
Most frequent serious events
EventPhenytoinValproateLevetiracetamNo Anticonvulsant
vasospasmNervous system disorders1/241/52/161/7
pulmonary edemaRespiratory, thoracic and mediastinal disorders0/240/50/161/7
cerebral infarctionNervous system disorders0/240/50/161/7
deep venous thrombosisVascular disorders1/240/51/160/7
hydrocephalusNervous system disorders1/240/51/160/7
drug feverImmune system disorders1/240/50/160/7
Most frequent other events
Most frequent other events
EventPhenytoinValproateLevetiracetamNo Anticonvulsant
urinary tract infectionInfections and infestations0/241/50/160/7

Baseline characteristics

Age, Continuous
Age, Continuous(years)PhenytoinValproateLevetiracetamNo AnticonvulsantTotal
Median48.5 (31 to 71)46 (26 to 62)51 (30 to 71)49 (44 to 75)48 (26 to 75)
Age, Categorical
Age, Categorical(Participants)PhenytoinValproateLevetiracetamNo AnticonvulsantTotal
<=18 years00000
Between 18 and 65 years22514546
>=65 years20226
Sex: Female, Male
Sex: Female, Male(Participants)PhenytoinValproateLevetiracetamNo AnticonvulsantTotal
Female14410634
Male1016118
Region of Enrollment
Region of Enrollment(participants)PhenytoinValproateLevetiracetamNo AnticonvulsantTotal
United States24516752
08

Study locations

No study locations are listed for this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 18, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00774306
Lead sponsor
Thomas Jefferson University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Responsible party
Sponsor
First posted
Oct 17, 2008
Start date
Apr 2009
Primary completion
Jun 2012
Completion
Jun 2012
Results posted
Nov 25, 2014
Last update
Dec 18, 2017

Study contacts

Scott Mintzer, MD
principal investigator · Assistant Professor of Neurology, Jefferson Comprehensive Epilepsy Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.

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