Outcome Study in Refractory Epilepsy (SOPHIE)

NCT03939507 | Completed

• 1 other identifier: FARM52K2WM_003
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy

Keywords

epilepsy,; outcome; antiepileptic drugs; toxicity

Outcome Measures

Primary Outcomes (2)

• Quality Of Life In Epilepsy (QOLIE)-31 global score

  The change in QOLIE-31 global score (final visit vs initial visit). QOLIE-31 is a widely used epilepsy-specific questionnaire

  Month 18

• Adverse Events Profiles (AEP) score

  The change in AEP score (final visit vs initial visit). The epilepsy-specific validated scale was used. Higher values represent a worse outcome.

  Month 18

Secondary Outcomes (13)

• Retention patients and AntiEpileptic Drugs (AEDs) added/substituted

  month 6, 12, 18

• Percentage of patients seizure free on each of the AEDs added/substituted

  month 6, 12

• Percentage of patients with 50% seizure reduction on each of the AEDs added/substituted

  month 6

• Percentage of patients free from seizures

  month 6, 12

• Percentage of patients with 50% seizure reduction

  month 6

Study Arms (2)

Intervention group

EXPERIMENTAL

AEP score results were made available to the treating physician at each assessment visit.

Other: AEP score available to the treating physician

Control group

NO INTERVENTION

AEP scores were only made available at the end of follow-up.

Interventions

AEP score available to the treating physician OTHER

the treating physician knew the AEP score results

Intervention group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- not seizures during the previous 6 months
• age \>16 years;
• no progressive disorder;
• ability to complete the Adverse Profile AEP questionnaire;
• an AEP score \>=45
• age \<16 years;
• progressive disorder;
• inability to complete the Adverse Profile AEP questionnaire;
• an AEP score \<45

Sponsors & Collaborators

• University of Pavia: lead
• University of Catanzaro: collaborator
• University of Bologna: collaborator

Study Sites (1)

Clinical Pharmacology Unit, University of Pavia

Pavia, 27100, Italy

Location

Related Publications (11)

• Beghi E, Gatti G, Tonini C, Ben-Menachem E, Chadwick DW, Nikanorova M, Gromov SA, Smith PE, Specchio LM, Perucca E; BASE Study Group. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res. 2003 Nov;57(1):1-13. doi: 10.1016/j.eplepsyres.2003.09.007.

  PMID: 14706729 BACKGROUND

• Beghi E, Garattini L, Ricci E, Cornago D, Parazzini F; EPICOS Group. Direct cost of medical management of epilepsy among adults in Italy: a prospective cost-of-illness study (EPICOS). Epilepsia. 2004 Feb;45(2):171-8. doi: 10.1111/j.0013-9580.2004.14103.x.

  PMID: 14738425 BACKGROUND

• Devinsky O, Vickrey BG, Cramer J, Perrine K, Hermann B, Meador K, Hays RD. Development of the quality of life in epilepsy inventory. Epilepsia. 1995 Nov;36(11):1089-104. doi: 10.1111/j.1528-1157.1995.tb00467.x.

  PMID: 7588453 BACKGROUND

• Jannuzzi G, Cian P, Fattore C, Gatti G, Bartoli A, Monaco F, Perucca E. A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy. Epilepsia. 2000 Feb;41(2):222-30. doi: 10.1111/j.1528-1157.2000.tb00144.x.

  PMID: 10691121 BACKGROUND

• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.

  PMID: 10660394 BACKGROUND

• Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002 Apr 23;58(8 Suppl 5):S9-20. doi: 10.1212/wnl.58.8_suppl_5.s9.

  PMID: 11971128 BACKGROUND

• Perucca E. Marketed new antiepileptic drugs: are they better than old-generation agents? Ther Drug Monit. 2002 Feb;24(1):74-80. doi: 10.1097/00007691-200202000-00013.

  PMID: 11805726 BACKGROUND

• Perucca E. An introduction to antiepileptic drugs. Epilepsia. 2005;46 Suppl 4:31-7. doi: 10.1111/j.1528-1167.2005.463007.x.

  PMID: 15968807 BACKGROUND

• Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology. 2004 Jan 13;62(1):23-7. doi: 10.1212/wnl.62.1.23.

  PMID: 14718691 BACKGROUND

• Johnson EK, Jones JE, Seidenberg M, Hermann BP. The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy. Epilepsia. 2004 May;45(5):544-50. doi: 10.1111/j.0013-9580.2004.47003.x.

  PMID: 15101836 BACKGROUND

• Franco V, Canevini MP, De Sarro G, Fattore C, Fedele G, Galimberti CA, Gatti G, La Neve A, Rosati E, Specchio LM, Striano S, Tinuper P, Perucca E; SOPHIE Study Group. Does screening for adverse effects improve health outcomes in epilepsy? A randomized trial. Neurology. 2020 Jul 21;95(3):e239-e246. doi: 10.1212/WNL.0000000000009880. Epub 2020 Jun 29.

  PMID: 32601123 DERIVED

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Emilio Perucca, Prof

  Clinical Pharmacology Unit, University of Pavia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: May 6, 2019
• Study Start: November 6, 2006
• Primary Completion: July 16, 2009
• Study Completion: July 16, 2009
• Last Updated: May 6, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)