Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW)
Summary
There are no guidelines on the first maintenance daily dose of antiepileptic drugs (AEDs) in newly diagnosed, previously untreated epilepsy. Original trials and Cochrane reviews show that seizure remission can be achieved with differing daily doses. In clinical practice, the first maintenance dose varies significantly. In contrast, the risk of adverse treatment effects increases with dosage. There is thus the need to identify the lowest effective dose for treatment start. This background prompted us to undertake a randomized multicenter pragmatic non-inferiority trial comparing standard to low daily doses of AEDs to demonstrate that low doses are at least as effective as standard doses (as indicated by the national formulary) but are better tolerated and are associated with a better quality of life. If proven as effective as the standard dose, a low daily dose of AEDs is a benefit to the patient in terms of tolerability and safety and a source of savings for the National Health System.
Timeline
- Start
- 2021-05-10
- Primary completion
- 2024-06-30
- Completion
- 2024-06-30
Publications
- Background Abimbola S, Martiniuk AL, Hackett ML, Anderson CS. The influence of design and definition on the proportion of general epilepsy cohorts with remission and intractability. Neuroepidemiology. 2011;36(3):204-12. doi: 10.1159/000327497. Epub 2011 May 24.
- Background Beghi E, Niero M, Roncolato M. Validity and reliability of the Italian version of the Quality-of-Life in Epilepsy Inventory (QOLIE-31). Seizure. 2005 Oct;14(7):452-8. doi: 10.1016/j.seizure.2005.07.008. Epub 2005 Aug 10.
- Background Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981 Aug;22(4):489-501. doi: 10.1111/j.1528-1157.1981.tb06159.x. No abstract available.
- Background Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshe SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14.
- 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.
- Background Maguire M, Marson AG, Ramaratnam S. Epilepsy (partial). BMJ Clin Evid. 2010 Jun 28;2010:1214.
- Background Perucca P, Jacoby A, Marson AG, Baker GA, Lane S, Benn EK, Thurman DJ, Hauser WA, Gilliam FG, Hesdorffer DC. Adverse antiepileptic drug effects in new-onset seizures: a case-control study. Neurology. 2011 Jan 18;76(3):273-9. doi: 10.1212/WNL.0b013e318207b073.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Carbamazepine | Small molecule | 300 mg | Oral |
| Subject | Carbamazepine | Small molecule | 600 mg | Oral |
| Subject | Gabapentin | Small molecule | 450 mg | Oral |
| Subject | Gabapentin | Small molecule | 900 mg | Oral |
| Subject | Lamotrigine | Small molecule | 100 mg | Oral |
| Subject | Lamotrigine | Small molecule | 200 mg | Oral |
| Subject | Levetiracetam | Other / unclassified | 500 mg | Oral |
| Subject | Levetiracetam | Other / unclassified | 1000 mg | Oral |
| Subject | Oxcarbazepine | Small molecule | 600 mg | Oral |
| Subject | Oxcarbazepine | Small molecule | 1200 mg | Oral |
| Subject | Topiramate | Small molecule | 100 mg | Oral |
| Subject | Topiramate | Small molecule | 200 mg | Oral |
| Subject | Valproate | Small molecule | 300 mg | Oral |
| Subject | Valproate | Small molecule | 600 mg | Oral |
| Subject | Zonisamide | Other / unclassified | 150 mg | Oral |
| Subject | Zonisamide | Other / unclassified | 300 mg | Oral |