1 Week Versus 6 Weeks of Levetiracetam in Surgical Brain Tumor Patients
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
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:
|
Active Comparator: 6 Week Levetiracetam Levetiracetam taken by mouth at a daily dose of 1000 mg for six weeks. |
Drug: Levetiracetam
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
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.- IRB201400876
- OCR14673
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
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
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 |
kristine.wynne@neurosurgery.ufl.edu |
- IRB201400876
- OCR14673