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Focal EpilepsyPhase 4STEP-ONENCT00438451

Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs

A Phase 4 study testing Levetiracetam, Carbamazepine and Lamotrigine in people with Focal Epilepsy, run by Johannes Gutenberg University Mainz at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Focal Epilepsy
What is being tested?
Levetiracetam, Carbamazepine and Lamotrigine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
361 participants
Where
1 siteGermany
Study dates
Jan 2007to Aug 2011
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Neurology, University of Mainz Medical Centre

    Mainz, 55101

Other trials in Germany

About this study

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.

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.

Read the 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).

Conditions
Focal Epilepsy
Being tested
Levetiracetam, Carbamazepine, Lamotrigine
Keywords
elderly, focal epilepsy, anticonvulsive, treatment, levetiracetam, lamotrigine, carbamazepine
Medical subject headings
Epilepsies, Partial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevetiracetamDrug

    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.

  • CarbamazepineDrug

    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.

  • LamotrigineDrug

    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.

Study groups in NCT00438451
Study groupRoleWhat they receive
LevetiracetamActive comparatorLevetiracetam
Receives: Drug: Levetiracetam
CarbamazepineActive comparatorCarbamazepine
Receives: Drug: Carbamazepine
LamotrigineActive comparatorLamotrigine
Receives: Drug: Lamotrigine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 58-week Retention Rate Measured by the Number of Drop Outs Due to Adverse Events or Seizures From Day 1 of Treatment

    Measured: 58 weeks

Secondary outcomes (11)

  1. Time to Drop Out

    number of days between randomization and premature discontinuation of the study

    Measured: 58 weeks

  2. Percentage of Patients Remaining Seizure-free at Week 30 (Visit 4)

    Percentage of patients experiencing no seizures until week 30 (Visit 4) and did not discontinue the study until week 30.

    Measured: Week 30

  3. Percentage of Patients Remaining Seizure Free at Week 58 (Visit 6)

    Percentage of patients experiencing no seizures until week 58 (Visit 6) and did not discontinue the study until week 58.

    Measured: week 58

  4. The Time (in Days) to First Break-through Seizure (From Day 1 of Treatment)

    Measured: over the whole duration of 58 weeks

  5. The Absolute Seizure Frequency During the Maintenance Phase (Weeks 7 - 58)

    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.

    Measured: over 52 weeks

  6. Proportion of Seizure-free Days During the Maintenance Phase for Subjects Who Enter the Maintenance Phase

    Measured: 52 weeks

  7. QOLIE-31 (Quality Of Life In Epilepsy) Results at V6

    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.

    Measured: 58 weeks, final visit

  8. Portland Neurotoxicity Scale (PNS) at V6

    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.

    Measured: at week 58

  9. Results of Cognitive Testing (EpiTrack© by UCB) - Score at V6

    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.

    Measured: week 58

  10. Results of Cognitive Testing (EpiTrack© by UCB) - Categories at V6

    Evaluation of current testing at V6:

    ≥29 score points: Inconspicuous; 26 to 28 score points: Borderline;

    ≤25 score points: Impaired

    Measured: 58 weeks

  11. Results of Cognitive Testing (EpiTrack© by UCB) - Changes to Baseline (V0) at Week 58 (V6)

    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

    Measured: week 58

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionJul 2010
  4. Study completionAug 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
361 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00438451
Sponsor's protocol ID
STEPONE05
Other IDs
ISRCTN: 94839639, EudraCT Number:2005-003324-19
Acronym
STEP-ONE
Status last verified
Jan 2013
First submitted
21 Feb 2007
Last updated
28 Feb 2013
Data monitoring committee
No

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. doi: 10.1212/01.WNL.0000167384.68207.3E.

    PubMed 15955935

  • 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. doi: 10.1046/j.1528-1157.2002.45401.x.

    PubMed 12199724

  • Werhahn KJ, Trinka E, Dobesberger J, Unterberger I, Baum P, Deckert-Schmitz M, Kniess T, Schmitz B, Bernedo V, Ruckes C, Ehrlich A, Kramer G. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia. 2015 Mar;56(3):450-9. doi: 10.1111/epi.12926. Epub 2015 Feb 12.

    PubMed 25684224

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Levetiracetam, Carbamazepine and Lamotrigine in people with Focal Epilepsy, run by Johannes Gutenberg University Mainz at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00438451, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2013.

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