A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice

Study Overview
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Brief Summary
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Assessment of the efficacy under daily clinical conditions of the new antiepileptic drugs (AEDs) gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine and topiramate, used as first-choice combination therapy (bitherapy) in patients with focal epilepsy.

Official Title
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Liceo Study: A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice

Conditions
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Focal Epilepsy

Intervention / Treatment
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* Drug: Gabapentin, Lamotrigine, Levetiracetam, Pregabalin, Oxcarbacepine, Tiagabine, Topiramate, Zonisamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older. Diagnosis of focal epilepsy. Previous failure of one or more AEDs used in monotherapy. Background treatment with an antiepileptic drug. The investigator has considered that the patient must start treatment with some of the seven new AEDs in combination therapy: lamotrigine, levetiracetam, gabapentin, oxcarbazepine, pregabalin, tiagabine and/or topiramate. History of seizures in the patient in the past 3 months. The patient or legal guardian must be able to understand the characteristics of the study and fill in the seizure diaries. Written informed consent. Exclusion Criteria: Inability to comply with the study requirements. Diagnosis of generalized epilepsy or inability to establish if focal or generalized. Presence of serious or uncontrolled systemic disease, serious psychiatric disease or progressive neurological disease. History of alcoholism, drug addiction, or abuse of medicines in the past two years. Psychogenic seizures in the two years prior to inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1.0<br> | Drug: Gabapentin, Lamotrigine, Levetiracetam, Pregabalin, Oxcarbacepine, Tiagabine, Topiramate, Zonisamide<br>* Gabapentin: up to 3.600 mg/d Lamotrigine: up to 400 mg/d Levetiracetam: up to 3.000 mg/d Pregabalin: up to 600 mg/d Oxcarbazepine: up to 2.400 mg/d Tiagabine: up to 30 mg/d Topiramate: up to 400 mg/d Zonisamide: up to 500 mg/d<br>* Other names: Neurontin, Lamictal, Lyrica, Keppra, Topamax, Gabatril, Episen, Zonegran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Classified as Responders | Responder = decrease in number of seizures by >=50 percent (%) during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the number of seizures that occurred during the 3 months before the baseline visit (baseline). | Baseline, Month 3, Month 6 (last 3 months of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Reduction in Number of Seizures >=25% and >=75% During the Last 3 Months of Treatment | Percent of participants with reduction in number of seizures >=25% and >=75% during the last 3 months of treatment before discontinuation (assessed at Month 3 and Month 6) versus the 3 month period before the baseline visit. | Baseline, Month 3, Month 6 (last 3 months of treatment) | 
| Percent of Seizure-free Participants During the Last 3 Months Before Discontinuation |  | Baseline, Month 3, Month 6 (last 3 months of treatment) | 
| Percent Change From Baseline in the Median Number of Seizures During the Last 3 Months of Treatment |  | Baseline, Month 3, Month 6 (last 3 months of treatment) | 
| Percent of Days Without Crisis During the Study | Crisis was defined as the total number of seizures during the study, the seizures at month 3 plus the seizures at month 6. The percent of days without crisis is number of days of study (date of last visit minus date of baseline visit) without crisis divided by number of days of study, multiplied by 100. | Baseline through Month 6 (or end of treatment) | 
| Time to First Seizure | Number of days to first seizure after baseline. | Baseline to Month 6 (or end of treatment) | 
| Percent of Participants Who Continued on Study Medication to Month 6 | Retention rate: percent of participants who continued on study medication throughout the 6 Month period after inclusion in the study. | Baseline to Month 6 | 
| Time to Discontinuation Due to Lack of Efficacy |  | Baseline, Month 3, Month 6 | 
| Time to Discontinuation Due to Safety, Tolerability, or Treatment Compliance |  | Baseline, Month 3, Month 6 | 
| Time to Discontinuation Due to Other Reasons |  | Baseline, Month 3, Month 6 | 
| Treatment Satisfaction Evaluated by Patient Global Impression of Change Visual Analog Scale (VAS) | Patient Global Impression of Change VAS: subject rated instrument to measure subject's change in overall status; range from 0 (much better) to 10 (much worse). | Baseline, Month 3, Month 6 | 
| Percent of Participants Reaching Monotherapy | Percent of participants who started on more than one treatment (bitherapy) and reached monotherapy by end of study. | Baseline through Month 6 (or end of study) | 
| Percent of Participants That Reduced, Maintained and Increased Their Doses of New Antiepileptic Drugs (AED) |  | Baseline to Month 6 (or end of treatment) | 
| Percent of Participants That Reduced, Maintained and Increased the Doses of the Initial Treatment Administered in Monotherapy |  | Baseline through Month 6 (or end of treatment) | 
| Change From Baseline to Month 6 in the Hospital Anxiety and Depression Scale (HADS) | HADS: subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Baseline to Month 6 | 
| Change From Baseline to Month 6 in Quality of Life 10 Domains (QOLIE-10) | QOLIE-10: 10-item questionnaire evaluates health-related quality of life in individuals with epliepsy. Comprised of 7 components: seizure worry, overall quality of life, emotional well-being, energy, cognitive functioning, medication effects (physical and mental effects), and social function (work, driving, social function). Total score rated 0 to 100; higher score = higher quality of life. | Baseline to Month 6 | 
| Change From Baseline to Months 3 and 6 in Health Condition: Euro Quality of Life Scale (EQ-5D) Visual Analog Scale (VAS) | Assessment of the health condition of the subjects using the EQ-5D VAS: subject rated questionnaire to assess health-related quality of life in terms of a single index value. Using the VAS subjects rated current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. | Baseline, Month 3, Month 6 | 
| Change in Sleep Disturbances From Baseline to Month 6: Medical Outcomes Study Sleep Scale (MOS-SS) | Subject rated instrument to assess key constructs of sleep; assesses sleep quality and quantity. Consists of a 6-item and 9-item overall sleep problems index measuring time to fall asleep and sleep duration in past 4 weeks; 5 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath, somnolence, and adequacy. Transformed scores range = 0 to 100; higher score indicates greater intensity of attribute. Two additional subscales = sleep quantity (range 0-24 hours) and optimal sleep (number of participants with optimal sleep 7-8 hours per night). | Baseline to Month 6 | 
| Percent of Participants Indicating Optimal Sleep on the Optimal Sleep Subscale: Medical Outcomes Study Sleep Scale (MOS-SS) | MOS-SS: subject rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality and is comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Optimal sleep subscale is derived from sleep quantity average hours of sleep over the past 4 weeks; percent of participants with response YES (optimal) if sleep quantilty was 7-8 hours of sleep per night. | Baseline, Month 6 | 
| Change From Baseline to Month 6 in Visits to a Specialist or the Emergency Room Because of Epilepsy | Numerical assessment of change in the number of visits to a specialist or the emergency room because of epilepsy needed during the study. | Baseline to Month 6 | 
| Change From Baseline to Month 6 in Total Number of Days Hospitalized Because of Epilepsy | Numerical assessment of change in total number of days hospitalized because of epilepsy during the study. | Baseline to Month 6 | 
| Percent of Participants With Cessation of Occupation, Requirement of Caregiver, or Admission to Intensive Care Unit | Percent of participants with cessation of usual occupation, requirement of an informal caregiver, and who required admission to the intensive care unit (ICU). | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy antiepileptic biotherapy