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Outcome Study in Refractory Epilepsy (SOPHIE) (SOPHIE)

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ClinicalTrials.gov Identifier: NCT03939507
Recruitment Status : Completed
First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
University of Catanzaro
University of Bologna
Information provided by (Responsible Party):
University of Pavia

Tracking Information
First Submitted Date  ICMJE April 18, 2019
First Posted Date  ICMJE May 6, 2019
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE November 6, 2006
Actual Primary Completion Date July 16, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Quality Of Life In Epilepsy (QOLIE)-31 global score [ Time Frame: Month 18 ]
    The change in QOLIE-31 global score (final visit vs initial visit). QOLIE-31 is a widely used epilepsy-specific questionnaire
  • Adverse Events Profiles (AEP) score [ Time Frame: Month 18 ]
    The change in AEP score (final visit vs initial visit). The epilepsy-specific validated scale was used. Higher values represent a worse outcome.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • Retention patients and AntiEpileptic Drugs (AEDs) added/substituted [ Time Frame: month 6, 12, 18 ]
    Retention of patients on each of the AEDs added/substituted
  • Percentage of patients seizure free on each of the AEDs added/substituted [ Time Frame: month 6, 12 ]
    Percentage of patients free achieving 6- and 12-month seizure remission on each of the AEDs added/substituted
  • Percentage of patients with 50% seizure reduction on each of the AEDs added/substituted [ Time Frame: month 6 ]
    Percentage of patients with 50% seizure reduction over 6 months (vs 3-month period before enrollment) on each of the AEDs added/substituted
  • Percentage of patients free from seizures [ Time Frame: month 6, 12 ]
    Percentage of patients free from seizures during the last 6 and 12 months of follow-up
  • Percentage of patients with 50% seizure reduction [ Time Frame: month 6 ]
    Percentage of patients with 50% seizure reduction (vs 3-month period before enrollment) during the last 6 months of follow-up
  • QOLIE-31 scores [ Time Frame: month 6, 12, 18 ]
    Changes in QOLIE-31 scores over time
  • Beck Depression Inventory (BDI) scores [ Time Frame: month 6, 12, 18 ]
    Changes in Beck Depression Inventory (BDI) scores over time. Higher values represent a worse outcome.
  • AEP scores [ Time Frame: month 6, 12, 18 ]
    Changes in Adverse Effect Profile (AEP) scores over time
  • Clinical Global Impression (CGI) scores [ Time Frame: month 6, 12, 18 ]
    Changes in CGI scores over time. CGI is a 5 digit global impression scale for clinical change, compiled separately by the physician and by the patient/caregiver.
  • Number of AEDs [ Time Frame: month 6, 12, 18 ]
    Number of AEDs changed/substituted over the follow-up period
  • Total drug load [ Time Frame: month 6, 12, 18 ]
    Changes in total drug load during follow-up. Drug loads, estimated as the sum of the prescribed daily dose (PDD)/defined daily dose (DDD) ratio for each AED included in the treatment regimen, where PDD is the prescribed daily dose and DDD is the defined daily dose, which corresponds to the assumed average maintenance daily dose of a drug used for its main indication.
  • Adverse effects [ Time Frame: month 6, 12, 18 ]
    Adverse effects, recorded over time, through general and neurological examination and non-structured interview.
  • Cost data [ Time Frame: month 6, 12, 18 ]
    Cost data are based on patient's records of laboratory tests, doctor's visits, specialist consultations treatments, hospital admissions and day-hospital days during follow up.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Outcome Study in Refractory Epilepsy (SOPHIE)
Official Title  ICMJE A Prospective Study on Long-term Outcome and Potential Usefulness fo an Intervention Aimed at Reducing Adverse Effects in Patients With Refractory Epilepsy
Brief Summary

Over 1 million people in the European Union (EU) suffer from chronic refractory epilepsy. Their quality of life (QoL) is severely affected by seizures and by the adverse effect of antiepileptic drug (AED) treatment. Several new AEDs have been introduced in recent years, but their impact on the long-term outcome in these patients has been inadequately explored. Preliminary data from the U.S. suggests that using a standardize toll to quantitate adverse AED effects can improve outcome, but the general applicability of these findings is unclear.

Objectives: 1) To assess prospectively AED utilization patterns in patients with refractory epilepsy ; 2) to assess how such treatments and other variables correlated with seizure control, adverse effects, and QoL in these patients; 3) to establish the impact of a standardized evaluation of adverse effects on clinical outcome.

Methods: The project included a core observational study and a randomized intervention in a subcohort.

In the core (observational) study, 1,000 consecutive refractory epilepsy patients were enrolled and followed-up prospectively at 10 centres in Italy. The following parameters were recorded at 0 (entry), 6, 12 and 18 months: (i) drug therapy; (ii) seizure frequency; (iii) adverse events based on medical examination and non-structured interview; (iii) treatment costs and, (iv) for patients above age 16, standardized questionnaires for adverse effects (AEP), depressive symptoms (Becks Depression Scale, BDS), QoL (QOLIE-31) and clinical global impression (CGI). The primary outcome (changes in QOLIE-31 scores) will be related to the other variables measured.

In the randomized intervention, the subcohort meeting specific eligibility criteria (age >16 years, no progressive disorder, AEP score>=45 ) was randomized to two groups. In the intervention group, AEP score results were made available to the physician at each visit, while in the other group AEP scores were only made available at the end of follow-up. Primary outcome were changes in AEP score.

Detailed Description

With a prevalence of about 0.8% in the general population, chronic active epilepsy is the most common serious neurological disorder and affects 3.7 million people in the EU alone. While the majority of patients with epilepsy can be fully controlled by available medications, about 40% fail to achieve seizure control. Refractory epilepsy is associated with poor quality of life (QoL), due to the consequences of seizures, the burden of adverse effects of antiepileptic drugs (AEDs), and associated comorbidities, especially depressed mood. In addition to human suffering, refractory epilepsy entails major costs: observational studies in Italy estimated an annual medical costs at 2,190 in adults, or 3,268 euros in children.

The study had a prospective design and mainly observational design (core study). A subgroup of patients, participated in a randomized assessment (controlled study) of the impact of utilizing a standardized tool for the assessment of adverse effects.

For the core study, the study population was represented by 1,000 consecutive consenting patients with refractory epilepsy seen as in- or outpatients at 10 major secondary/tertiary referral centres in Italy. "Refractory epilepsy" was defined as "the persistence of seizures after adequate attempts with the maximally tolerated dosage of one or more appropriate primary AEDs, excluding situations where a meaningful dose escalation was prevented by allergic or idiosyncratic adverse reactions" and at least one seizure during the previous 3 months while at steady state on the current treatment schedule. The degree of refractoriness was classified into categories.

A subcohort of patients included in the study took part in a randomized assessment of the usefulness of providing the treating physician with a standardized assessment of the adverse effect profile. The subcohort was represented by all patients enrolled in the core study who met at the first assessment visit the following additional eligibility criteria: (i) age >16 years; (ii) no progressive disorder; (iii) ability to complete the Adverse Profile AEP questionnaire, and (iv) an AEP score >=45.

For the core study, the approach was observational and the study did not interfere with clinical management. All patients were treated as considered best by the attending physician. Results of questionnaires were not made available to the treating physician until the end of the study, except for the AEP questionnaire data that were fed back to the physician only for a subgroup of patients included in the randomized assessment.

In the randomized assessment, patients meeting eligibility were randomized to two groups. In the intervention group, AEP score results were made available to the treating physician at each assessment visit, while in the other group AEP scores were only made available at the end of follow-up. Evaluations were identical to those carried out in the core study.

Except for making available the AEP scores to the treating physician, the procedures used for the collection and the handling of the information were identical in the core study and the randomized assessment. Patients were seen in the clinic at the following times: 0 (enrolment), 6, 12 and 18 months. At the first visit, detailed information were collected about demographics, medical history and current medical status. At this visit and at each of the other visits, the following information were collected:

  • QOLIE-31 scores (only patients aged >16years), using the validated epilepsy-specific questionnaire, which is the most widely used for QoL tool in epilepsy in different countries;
  • BDI scores (only patients aged >16years), using the validated inventory developed by Beck (1961), shown to have reliability and sensitivity in different settings, including refractory epilepsy ;
  • AEP scores (only patients aged >16years), using the epilepsy-specific validated scale developed by prof. Baker ;
  • A 5 digit Global Impression Scale for clinical change, compiled separately by the physician and by the patient/caregiver;
  • Seizure frequency, by using seizure diaries compiled by patients and/or caregivers.
  • Adverse effects, through general and neurological examination and non-structured interview;
  • Drug treatment details (including, when available, serum AED levels), from the prescriber and patient's interview, and drug load scores as described by prof. Deckers;
  • Items to be used for cost calculations, based on patient's records of laboratory tests, doctor's visits, specialist consultations, treatments, hospital admissions, and day-hospital days during follow up.

The study duration was 36 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
In the randomized assessment, patients meeting eligibility were randomized to two groups. In the intervention group, AEP score results were made available to the treating physician at each assessment visit, while in the other group AEP scores were only made available at the end of follow-up.
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Epilepsy
Intervention  ICMJE Other: AEP score available to the treating physician
the treating physician knew the AEP score results
Study Arms  ICMJE
  • Experimental: Intervention group
    AEP score results were made available to the treating physician at each assessment visit.
    Intervention: Other: AEP score available to the treating physician
  • No Intervention: Control group
    AEP scores were only made available at the end of follow-up.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2019)
1000
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 16, 2009
Actual Primary Completion Date July 16, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Core study:

Inclusion Criteria:

  • an established diagnosis of epilepsy;
  • drug refractoriness, defined as persistence of seizures after adequately applied treatment(s) with one or more appropriate AEDs at maximally tolerated doses, excluding treatments whereby idiosyncratic reactions prevented titration to usually effective dosages;
  • at least one seizure during the previous 6 months while at steady state on the currently used AED regimen;
  • written informed consent.

Exclusion Criteria:

- not seizures during the previous 6 months

Inclusion Criteria for a subgroup of patients, who took part in a randomized assessment:

  • age >16 years;
  • no progressive disorder;
  • ability to complete the Adverse Profile AEP questionnaire;
  • an AEP score >=45

Exclusion criteria:

  • age <16 years;
  • progressive disorder;
  • inability to complete the Adverse Profile AEP questionnaire;
  • an AEP score <45
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03939507
Other Study ID Numbers  ICMJE FARM52K2WM_003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Pavia
Study Sponsor  ICMJE University of Pavia
Collaborators  ICMJE
  • University of Catanzaro
  • University of Bologna
Investigators  ICMJE
Study Director: Emilio Perucca, Prof Clinical Pharmacology Unit, University of Pavia
PRS Account University of Pavia
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP