Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
Information source: Johannes Gutenberg University Mainz
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Focal Epilepsy
Intervention: levetiracetam (Drug); carbamazepine slow release (Drug); lamotrigine (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Johannes Gutenberg University Mainz Official(s) and/or principal investigator(s):
Konrad J Werhahn, MD, Study Chair, Affiliation: Johannes Gutenberg University, Department od Neurology
Günter Kraemer, MD, Study Director, Affiliation: Swiss Epilepy Centre
Eugen Trinka, MD, Study Director, Affiliation: Medical University of Innsbruck, Department of Neurology
Overall contact:
Konrad J Werhahn, MD, Phone: +49-(0)6131-17-, Ext: 5275, Email: werhahn@uni-mainz.de
Summary
In this clinical trial patients with newly diagnosed focal epilepsy aged 60 years or older
receive three different antiepileptic drugs in a double-blind, randomized design over a
period of 58 weeks. All drugs are licensed for the treatment of epilepsy. The primary
endpoint of this study will be retention rate at 58-weeks, since it reflects both efficacy
and tolerability.
Clinical Details
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.
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: 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)
Detailed description:
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).
Eligibility
Minimum age: 60 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age 60 yrs or above.
- 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 at
least 2 epileptic seizures, one of which occurring in the last 6 months prior
inclusion.
- No previous AED treatment, except for a period not longer than 4 weeks prior to
inclusion (V0).
- Ability of subject to understand verbal and written instructions, to comply with all
study requirements, and to comprehend character and individual consequences of the
clinical trial.
- Written informed consent before enrolment in the trial.
Exclusion Criteria:
- Acute symptomatic epileptic seizures occurring acutely within a 2 week period after
the onset of an acute illness such as cerebral haemorrhage, cerebral infarct, rapid
progressive malignancy or other acute brain abnormalities (i. e. encephalitis, hypoxic
brain damage, trauma, metabolic derangement, following brain surgery).
- Dementia (as defined by history)
- Renal insufficiency as defined by GFR < 50 mL/min.
- Increased liver enzymes (GOT, GPT, gGT) or increased bilirubin ≥ 2-fold the upper
limit of normal (ULN).
- Pre-treatment with valproic acid within the four weeks prior inclusion (V0).
- Contraindication against or history of hypersensitivity to any of the investigational
medicinal products or to any drug with similar chemical structure or to any excipient
present in the pharmaceutical form of the investigational medicinal products.
- Participation in other clinical trials and observation period of competing trials
within the last 2 months, respectively.
- History of drug or alcohol abuse within the last 2 years.
- Medical condition which interferes with the participation in the trial according to
the opinion of the investigator.
- Patients with life expectancy < 1 year due to malignant disease
- Psychiatric morbidity requiring legal guardianship.
Locations and Contacts
Konrad J Werhahn, MD, Phone: +49-(0)6131-17-, Ext: 5275, Email: werhahn@uni-mainz.de
Department of Neurology, University of Mainz Medical Centre, Mainz 55101, Germany; Recruiting
Konrad J Werhahn, MD, Phone: +49(0)6131-17-, Ext: 5275, Email: werhahn@uni-mainz.de
Heike Hofmann, SN, Phone: +49(0)6131-17-, Ext: 2222, Email: hofmanh@uni-mainz.de
Konrad J Werhahn, MD, Principal Investigator
Patrick Pittermann, MD, Sub-Investigator
Katharina Schmidt, MD, Sub-Investigator
Sven Klimpe, MD, Sub-Investigator
Additional Information
www site of STEP-ONE trial
Related publications: Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, Spitz M, Frederick T, Towne A, Carter GS, Marks W, Felicetta J, Tomyanovich ML; VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(11):1868-73. Brodie MJ, Chadwick DW, Anhut H, Otte A, Messmer SL, Maton S, Sauermann W, Murray G, Garofalo EA; Gabapentin Study Group 945-212. Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy. Epilepsia. 2002 Sep;43(9):993-1000.
Starting date: January 2007
Ending date: December 2008
Last updated: November 6, 2007
|
