Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs (STEP-ONE)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Multicentre, Double-blind, Randomized, Phase IV Clinical Trial Comparing the Safety, Tolerability and Efficacy of Levetiracetam Versus Lamotrigine and Carbamazepine in the Oral Antiepileptic Therapy of Newly Diagnosed Elderly Patients With Focal Epilepsy.|
- 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment [ Time Frame: 58 weeks ] [ Designated as safety issue: No ]
- Time to Drop Out [ Time Frame: 58 weeks ] [ Designated as safety issue: No ]number of days between randomization and premature discontinuation of the study
- Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4) [ Time Frame: Week 30 ] [ Designated as safety issue: No ]Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30.
- Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6) [ Time Frame: week 58 ] [ Designated as safety issue: No ]Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58.
- The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment) [ Time Frame: over the whole duration of 58 weeks ] [ Designated as safety issue: No ]
- The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58) [ Time Frame: over 52 weeks ] [ Designated as safety issue: No ]
Seizure frequency was assessed by investigators in the CRF at the Visits V3, V4, V5 and V6.
The absolute seizure frequency during the maintenance phase was defined as the sum of those entries.
- Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
- QOLIE-31 (Quality Of Life In Epilepsy) Results at V6 [ Time Frame: 58 weeks, final visit ] [ Designated as safety issue: No ]The QOLIE-31 is a 31 item score that measures the quality of life in epilepsy (each item with a range of 0 to 100). There are 7 sub-scores seizure worry (items 11,21,22,23,25), overall quality of life (items 1,14), emotional well-being (items 3,4,5,7,9), energy/fatigue (items 2,6,8,10), cognitive functioning (items 12,15,16,17,18,26), medication effects (items 24,29,30) and social functioning (13,19,20,27,28). These scores were combined to a total score by Total score = seizure worry*0.08 + overall quality of life*0.14 + emotional well-being*0.15 + energy/fatigue*0.12 + cognitive functioning*0.27 + medication effects*0.03 + social functioning*0.21 For all scores, higher values indicate better quality of life. Each score has a possible range from 0 to 100.
- Portland Neurotoxicity Scale (PNS) at V6 [ Time Frame: at week 58 ] [ Designated as safety issue: No ]
The PNS is a 15-item scale. Each item can be scored from 1 to 9. There are a total score (includes all items, range:15 to 135) and two subscores: The cognitive toxicity subscore (10 items: Energy Level, Memory, Interest, Concentration, Forgetfulness, Sleepliness, Moodiness, Alertness, Attention Span, Motivation, range:10 to 90) and the somatomoto subscore (5 items: Vision, Walking, Coordination, Tremor, Speech, range:5-45). The score is calculated by taking the mean of all non-missing values times the number of items.
Lower values indicate better quality of life.
- Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6 [ Time Frame: week 58 ] [ Designated as safety issue: No ]EPITrack-Score shows the performance of attention and executive functions. Higher values indicate a better performance. The results of EPITrack Score ranges between 7 and 45.
- Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6 [ Time Frame: 58 weeks ] [ Designated as safety issue: No ]
Evaluation of current testing at V6:
≥29 score points: Inconspicuous; 26 to 28 score points: Borderline;
≤25 score points: Impaired
- Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6) [ Time Frame: week 58 ] [ Designated as safety issue: No ]
Evaluation of Changes
Changes in the EpiTrack® Score were categorized as follows:
≥5 score points: Improved;
-3 to 4 score points: Unchanged;
≤-4 score points: Worsened
|Study Start Date:||January 2007|
|Study Completion Date:||August 2011|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Levetiracetam
LEV 250 mg capusles: week 1 and 2 0-0-1, week 3 and 4 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 per day (500 - 3000 mg)during maintenance.
Active Comparator: Carbamazepine
CBZ 100 mg capusles: week 1 and 2: 0-0-1, week 3 and 4: 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 per day (200 - 1200 mg) during maintenance depending on tolerance and efficacy.
Active Comparator: Lamotrigine
LTG 25 mg encapsulated: week 1 and 2: 0-0-1, week 3 and 4: 1-0-1, week 5: 1-0-2, week 6: 2-0-2. Patients may take 2 to 12 caps. per day (50 - 300 mg)during maintenance depending on tolerance and efficacy.
Indication: Focal Epilepsy Objectives: To evaluate the tolerability and efficacy of levetiracetam (LEV) in newly diagnosed elderly patients (aged 60 yrs or above) with focal epilepsy compared to lamotrigine (LTG) or carbamazepine slow release (CBZ).
Primary Outcome: The primary outcome will be the 58-week retention rate measured by the number of drop outs due to adverse events or seizures from day 1 of treatment.
Secondary Outcome: Proportion of patients remaining seizure-free at week 30 (Visit 4); proportion of patients remaining seizure free at week 58 (Visit 6); the time (in days) to first break-through seizure (from day 1 of treatment); the absolute seizure frequency during the maintenance (over 52 weeks) phase; proportion of seizure-free days during the maintenance phase for subjects who enter the maintenance phase; the frequency of adverse events (from day 1 of treatment); QOLIE-31 results at V6; Portland Neurotoxicity scale at V6; results of cognitive testing (EpiTrack© by UCB).
Trial Design: This is a randomized, double-blind, multicenter Phase IV study using a parallel group design with three treatment groups. The study will consist of a 6-week titration-phase and a 52-week maintenance phase. Patients who successfully complete the trial (final visit, V6) will be unblinded and offered either to continue on their current drug or be changed to an alternative antiepileptic drug (AED) treatment of choice.
Population: Patients aged 60 years or above with new onset focal epilepsy i.e. either at least one epileptic seizure in the last 6 months and focal epileptiform discharges on EEG or a relevant lesion on CT/MRI or a total of 2 epileptic seizures, one of which occurring in the last 6 months prior inclusion. Patients with acute (< 2 weeks) symptomatic epileptic seizures due to acute brain abnormalities (i.e. haemorrhage or cerebral infarct), or contraindications against any of the drugs in trial will be excluded.
Sample Size: 360 patients to be included, 120 patients per treatment arm. Investigational Medicinal Product(s): Levetiracetam, lamotrigine, carbamazepine-slow release Trial Duration and Dates: Duration of treatment: 6 weeks titration phase, 52 weeks maintenance phase.
Follow up: At the end of trial subjects will be unblinded and may choose to continue on the medication or taper the trial medication and be treated with an alternative drug at the investigators discretion. The patient will receive a dosing schedule and a referral letter for his/her physician.
Duration of trial: approximately 2 years. Start of recruitment: January 2007 Projected number of centres: 75 Number of countries: 3 (Germany, Switzerland, Austria).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00438451
|Department of Neurology, University of Mainz Medical Centre|
|Mainz, Germany, 55101|
|Study Chair:||Konrad J Werhahn, MD||Johannes Gutenberg University, Department od Neurology|
|Study Director:||Günter Kraemer, MD||Swiss Epilepy Centre|
|Study Director:||Eugen Trinka, MD||Medical University of Salzburg, Department of Neurology, Austria|