Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW)

NCT ID: NCT03689114

Last Updated: 2025-07-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-10

Study Completion Date

2024-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Epilepsies, Partial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a multicenter randomized pragmatic parallel-group single-blind non-inferiority trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Low dose

Dosage is in mg: low dose carbamazepine, 300 ; low dose levetiracetam, 500; low dose valproate, 300; low dose zonisamide, 150; low dose oxcarbazepine, 600; low dose topiramate, 100; low dose lamotrigine, 100; low dose gabapentin, 450. Study drugs are in form of tablets for daily administration. Study drug administration duration is 12 months. The choice of the drug is left to the caring physician's discretion but it must be limited to the AEDs marketed for monotherapy use. All the study drugs will be used according to the respective SPCs, which will be sent by the promoter to all the study investigators.

Group Type EXPERIMENTAL

Low dose carbamazepine

Intervention Type DRUG

Carbamazepine, 300 mg/die

Low dose levetiracetam

Intervention Type DRUG

Levetiracetam 500 mg/die

Low dose valproate

Intervention Type DRUG

Valproate 300 mg/die

Low dose zonisamide

Intervention Type DRUG

Zonisamide 150 mg/die

Low dose oxcarbazepine

Intervention Type DRUG

Oxcarbazepine 600 mg/die

Low dose topiramate

Intervention Type DRUG

Topiramate 100 mg/die

Low dose lamotrigine

Intervention Type DRUG

Lamotrigine 100 mg/die

Low dose gabapentin

Intervention Type DRUG

Gabapentin 450 mg/die

Standard dose

Dosage is in mg: standard dose carbamazepine 600; standard dose levetiracetam 1000; standard dose valproate, 600; standard dose zonisamide 300; standard dose oxcarbazepine 1200; standard dose topiramate, 200; standard dose lamotrigine, 200; standard dose gabapentin 900. Study drugs are in form of tablets for daily administration. Study drug administration duration is 12 months. The choice of the drug is left to the caring physician's discretion but it must be limited to the AEDs marketed for monotherapy use. All the study drugs will be used according to the respective SPCs, which will be sent by the promoter to all the study investigators.

Group Type ACTIVE_COMPARATOR

Standard dose carbamazepine

Intervention Type DRUG

Carbamazepine 600 mg/die

Standard dose levetiracetam

Intervention Type DRUG

Levetiracetam 1000 mg/die

Standard dose valproate

Intervention Type DRUG

Valproate 600 mg/die

Standard dose zonisamide

Intervention Type DRUG

Zonisamide 300 mg/die

Standard dose oxcarbazepine

Intervention Type DRUG

Oxcarbazepine 1200 mg/die

Standard dose topiramate

Intervention Type DRUG

Topiramate 200 mg/die

Standard dose lamotrigine

Intervention Type DRUG

Lamotrigine 200 mg/die

Standard dose gabapentin

Intervention Type DRUG

Gabapentin 900 mg/die

Interventions

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Low dose carbamazepine

Carbamazepine, 300 mg/die

Intervention Type DRUG

Standard dose carbamazepine

Carbamazepine 600 mg/die

Intervention Type DRUG

Low dose levetiracetam

Levetiracetam 500 mg/die

Intervention Type DRUG

Standard dose levetiracetam

Levetiracetam 1000 mg/die

Intervention Type DRUG

Low dose valproate

Valproate 300 mg/die

Intervention Type DRUG

Standard dose valproate

Valproate 600 mg/die

Intervention Type DRUG

Low dose zonisamide

Zonisamide 150 mg/die

Intervention Type DRUG

Standard dose zonisamide

Zonisamide 300 mg/die

Intervention Type DRUG

Low dose oxcarbazepine

Oxcarbazepine 600 mg/die

Intervention Type DRUG

Standard dose oxcarbazepine

Oxcarbazepine 1200 mg/die

Intervention Type DRUG

Low dose topiramate

Topiramate 100 mg/die

Intervention Type DRUG

Standard dose topiramate

Topiramate 200 mg/die

Intervention Type DRUG

Low dose lamotrigine

Lamotrigine 100 mg/die

Intervention Type DRUG

Standard dose lamotrigine

Lamotrigine 200 mg/die

Intervention Type DRUG

Low dose gabapentin

Gabapentin 450 mg/die

Intervention Type DRUG

Standard dose gabapentin

Gabapentin 900 mg/die

Intervention Type DRUG

Other Intervention Names

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low carbamazepine Standard carbamazepine Low levetiracetam Standard levetiracetam Low valproate Standard valproate Low zonisamide Standard zonisamide Low oxcarbazepine Standard oxcarbazepine Low topiramate Standard topiramate Low lamotrigine Standard lamotrigine Low gabapentin Standard gabapentin

Eligibility Criteria

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Inclusion Criteria

1. Age 18 years or older;
2. Newly diagnosed previously untreated epilepsy, defined according to the ILAE definition (Fisher et al, 2014);
3. Having experienced focal seizures, defined according to the ILAE criteria (Commission, 1981);
4. Able to understand and comply with the study requirements and release a written informed consent.

Exclusion Criteria

A patient will be excluded if at least one of the following criteria will be met:

1. Age less than 18 years;
2. Having experienced primarily or secondarily generalized tonic and/or clonic seizures, or other (non-focal) seizure types;
3. Previous exposure to AEDs;
4. Requiring low or standard doses on account of individual needs;
5. Inability to understand the aims or modalities of the study;
6. Current pregnancy or planning to become pregnant during the study period (e.g. who are not post-menopausal, surgically sterile, or using inadequate birth control). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause;
7. Previous treatment with an antiepileptic drug;
8. Men unable to practice contraception for the duration of the treatment.
9. Poor compliance with assigned treatments;
10. Refusal to release written informed consent;
11. The study investigators will receive the summary of product characteristics (SPC) available for each study drug. Patients cannot be enrolled in the study if the contraindications/warnings described in the SPC are met.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera San Gerardo di Monza

OTHER

Sponsor Role collaborator

Ministry of Health, Italy

OTHER_GOV

Sponsor Role collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ettore Beghi, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Di Ricerche Farmacologiche Mario Negri

Locations

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ASST Monza Ospedale San Gerardo

Monza, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 21606654 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16098770 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6790275 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24730690 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11971128 (View on PubMed)

Maguire M, Marson AG, Ramaratnam S. Epilepsy (partial). BMJ Clin Evid. 2010 Jun 28;2010:1214.

Reference Type BACKGROUND
PMID: 21429248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21242496 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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STANDLOW

Identifier Type: -

Identifier Source: org_study_id

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