1 Week Versus 6 Weeks of Levetiracetam in Surgical Brain Tumor Patients

Sponsor
University of Florida (Other)
Overall Status
Completed
CT.gov ID
NCT02334722
Collaborator
(none)
81
1
2
62.1
1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to see if there are any differences in patient reported neurotoxicity between patients who receive Levetiracetam tablets for one week after surgery to remove a brain tumor versus those who receive Levetiracetam tablets for six weeks after surgery. Specifically, we will see if one group has less side effects than the other, and whether or not one group has more seizures than the other.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Because seizures are one of the leading neurologic complications in brain tumor patients, neurosurgeons prescribe antiepileptic drugs (AEDs) to help prevent them. Although the American Academy of Neurology (AAN) guidelines recommend that AEDs be stopped after the first post-operative week in patients without seizures, there is no standard length of treatment and some patients may stay on AEDs indefinitely.

In an attempt to develop clinical guidelines for AED use in post-operative brain tumor patients, we will try to determine if taking levetiracetam for 1 week results in less neurotoxicity than taking it for 6 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
81 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Shortened Antiepileptic Drug (AED) Course in Surgical Brain Tumor Patients: A Randomized Trial
Actual Study Start Date :
Aug 5, 2015
Actual Primary Completion Date :
Oct 7, 2020
Actual Study Completion Date :
Oct 7, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1 Week Levetiracetam

Levetiracetam taken by mouth at a daily dose of 1000 mg for one week.

Drug: Levetiracetam
Other Names:
  • Keppra
  • Active Comparator: 6 Week Levetiracetam

    Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks.

    Drug: Levetiracetam
    Other Names:
  • Keppra
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Neurotoxicity Scale Scores [Baseline to 6 weeks]

      The Neurotoxicity Scale is as a validated 27 question, patient-reported measure for assessing the adverse effects of antiepileptic drugs on cognitive function. Patients self-report "no problem", "a mild problem", "a moderate problem" or "a serious problem" for each question corresponding to a score of 0, 1, 2, and 3, respectively. For each patient, the overall score was formed by summing scores in all 27 questions. The minimum possible score is 0 and the maximum possible total score is 81. A lower score indicates less toxicity when taking an antiepileptic drug. The outcome is a score change from baseline at the 6 week follow-up and is calculated by subtracting the baseline score from the 6 week follow-up score for each patient.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Adult (>18 years of age and older) patients who have or will have undergone surgical resection or biopsy of a supratentorial brain tumor and are able to consent for themselves.

    • Able to be randomized prior to or up to 48 hours after surgery.

    Exclusion Criteria:
    • No known history of seizure activity.

    • Pregnant or breastfeeding.

    • Renal dysfunction (CrCl < 30ml/min).

    • Beck's Depression Inventory (BDI) ≥14

    • Allergy to levetiracetam.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Florida Gainesville Florida United States 32610

    Sponsors and Collaborators

    • University of Florida

    Investigators

    • Principal Investigator: Maryam Rahman, MS, MD, University of Florida

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT02334722
    Other Study ID Numbers:
    • IRB201400876
    • OCR14673
    First Posted:
    Jan 8, 2015
    Last Update Posted:
    Dec 15, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details The first subject was enrolled in this trial on 8/5/2015 and the last on 8/27/2020 at an academic medical center in a Neurosurgical inpatient/outpatient setting. Potential participants were adult (>18 years of age and older) patients, with no seizure history, who had or will have had undergone surgical resection of a supratentorial brain tumor and were able to consent for themselves.
    Pre-assignment Detail
    Arm/Group Title 1 Week Levetiracetam 6 Week Levetiracetam
    Arm/Group Description Levetiracetam taken by mouth at a daily dose of 1000 mg for one week. Levetiracetam Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks. Levetiracetam
    Period Title: Overall Study
    STARTED 40 41
    COMPLETED 33 34
    NOT COMPLETED 7 7

    Baseline Characteristics

    Arm/Group Title 1 Week Levetiracetam 6 Week Levetiracetam Total
    Arm/Group Description Levetiracetam taken by mouth at a daily dose of 1000 mg for one week. Levetiracetam Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks. Levetiracetam Total of all reporting groups
    Overall Participants 40 41 81
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.8
    (13.7)
    49.9
    (17.1)
    54.8
    (16.2)
    Sex: Female, Male (Count of Participants)
    Female
    22
    55%
    17
    41.5%
    39
    48.1%
    Male
    18
    45%
    24
    58.5%
    42
    51.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    5%
    2
    4.9%
    4
    4.9%
    Not Hispanic or Latino
    37
    92.5%
    39
    95.1%
    76
    93.8%
    Unknown or Not Reported
    1
    2.5%
    0
    0%
    1
    1.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    5%
    3
    7.3%
    5
    6.2%
    White
    37
    92.5%
    38
    92.7%
    75
    92.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    2.5%
    0
    0%
    1
    1.2%
    Region of Enrollment (participants) [Number]
    United States
    40
    100%
    41
    100%
    81
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Neurotoxicity Scale Scores
    Description The Neurotoxicity Scale is as a validated 27 question, patient-reported measure for assessing the adverse effects of antiepileptic drugs on cognitive function. Patients self-report "no problem", "a mild problem", "a moderate problem" or "a serious problem" for each question corresponding to a score of 0, 1, 2, and 3, respectively. For each patient, the overall score was formed by summing scores in all 27 questions. The minimum possible score is 0 and the maximum possible total score is 81. A lower score indicates less toxicity when taking an antiepileptic drug. The outcome is a score change from baseline at the 6 week follow-up and is calculated by subtracting the baseline score from the 6 week follow-up score for each patient.
    Time Frame Baseline to 6 weeks

    Outcome Measure Data

    Analysis Population Description
    All patients taking levetiracetam 1000 mg daily, not stratified by dosing schedule.
    Arm/Group Title 1 Week Levetiracetam 6 Week Levetiracetam
    Arm/Group Description Levetiracetam taken by mouth at a daily dose of 1000 mg for one week. Levetiracetam Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks. Levetiracetam
    Measure Participants 33 34
    Median (Full Range) [score on scale]
    -1
    -3.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection 1 Week Levetiracetam, 6 Week Levetiracetam
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7824
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value -2.5
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Adverse events will be collected from first dose of study drug to six week evaluation or sooner if the patient contacts their physician/study team about new symptoms/problems.
    Adverse Event Reporting Description Participants at risk for all-cause mortality included any participant who signed consent to take part in the study. Participants at risk for Serious Adverse Events and Other (not including serious) Adverse Events included only participants who received study intervention.
    Arm/Group Title 1 Week Levetiracetam 6 Week Levetiracetam
    Arm/Group Description Levetiracetam taken by mouth at a daily dose of 1000 mg for one week. Levetiracetam Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks. Levetiracetam
    All Cause Mortality
    1 Week Levetiracetam 6 Week Levetiracetam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/40 (5%) 0/41 (0%)
    Serious Adverse Events
    1 Week Levetiracetam 6 Week Levetiracetam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/39 (28.2%) 7/37 (18.9%)
    Gastrointestinal disorders
    Bowel Obstruction 0/39 (0%) 0 1/37 (2.7%) 1
    Dysphagia 1/39 (2.6%) 1 0/37 (0%) 0
    Infections and infestations
    Meningitis 1/39 (2.6%) 1 0/37 (0%) 0
    Sepsis 0/39 (0%) 0 1/37 (2.7%) 1
    Metabolism and nutrition disorders
    Hyperglycemia 1/39 (2.6%) 1 0/37 (0%) 0
    Hyponatremia 1/39 (2.6%) 1 0/37 (0%) 0
    Musculoskeletal and connective tissue disorders
    Hip Pain 1/39 (2.6%) 1 0/37 (0%) 0
    Nervous system disorders
    Aphasia 3/39 (7.7%) 3 0/37 (0%) 0
    Cerebral edema 0/39 (0%) 0 1/37 (2.7%) 1
    Hydrocephalus 3/39 (7.7%) 3 1/37 (2.7%) 1
    Weakness 0/39 (0%) 0 1/37 (2.7%) 1
    Pseudomeningocele 0/39 (0%) 0 1/37 (2.7%) 1
    Hemiparesis 1/39 (2.6%) 1 0/37 (0%) 0
    Seizure 2/39 (5.1%) 2 0/37 (0%) 0
    Confusion 1/39 (2.6%) 1 0/37 (0%) 0
    Mental Status Change 1/39 (2.6%) 1 1/37 (2.7%) 1
    Psychiatric disorders
    Suicidal Ideation 1/39 (2.6%) 1 0/37 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism 1/39 (2.6%) 1 0/37 (0%) 0
    Vascular disorders
    Spinal Hematoma 0/39 (0%) 0 1/37 (2.7%) 1
    Other (Not Including Serious) Adverse Events
    1 Week Levetiracetam 6 Week Levetiracetam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/39 (69.2%) 22/37 (59.5%)
    Eye disorders
    Vision Change 2/39 (5.1%) 2 3/37 (8.1%) 3
    Gastrointestinal disorders
    Constipation 3/39 (7.7%) 3 1/37 (2.7%) 1
    Nausea 7/39 (17.9%) 7 5/37 (13.5%) 5
    Facial Swelling 3/39 (7.7%) 3 2/37 (5.4%) 2
    General disorders
    Fatigue 6/39 (15.4%) 7 8/37 (21.6%) 9
    Incision Pain 3/39 (7.7%) 3 3/37 (8.1%) 3
    Nervous system disorders
    Headache 9/39 (23.1%) 9 6/37 (16.2%) 6
    Confusion 3/39 (7.7%) 4 5/37 (13.5%) 6
    Aphasia 2/39 (5.1%) 2 2/37 (5.4%) 2
    Seizure 2/39 (5.1%) 2 2/37 (5.4%) 3
    Psychiatric disorders
    Insomnia 2/39 (5.1%) 2 4/37 (10.8%) 4
    Mental Status Change 4/39 (10.3%) 4 3/37 (8.1%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Kristine Wynne
    Organization University of Florida
    Phone 352-273-9727
    Email kristine.wynne@neurosurgery.ufl.edu
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT02334722
    Other Study ID Numbers:
    • IRB201400876
    • OCR14673
    First Posted:
    Jan 8, 2015
    Last Update Posted:
    Dec 15, 2021
    Last Verified:
    Dec 1, 2021