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

NCT03689114 | Completed Phase 4 Results DMC

• 1 other identifier: STANDLOW
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Epilepsies, Partial

Keywords

epilepsy; antiepileptic drugs; low dose; standard dose; new diagnosis

Outcome Measures

Primary Outcomes (1)

• Treatment Failure

  The proportion of patients experiencing a treatment failure motivated by the need to change the assigned dose or the assigned drug for seizure relapse during the follow-up. All proportions are reported as percentages.

  12 months

Secondary Outcomes (4)

• Drug-related Adverse Events

  12 months

• PSQ-18, Italian Version

  12 months

• QoLIE-31, Italian Version

  12 months

• Health Care Resources Utilization.

  12 months

Study Arms (2)

Low dose

EXPERIMENTAL

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.

Drug: Low dose carbamazepine; Drug: Low dose levetiracetam; Drug: Low dose valproate; Drug: Low dose zonisamide; Drug: Low dose oxcarbazepine; Drug: Low dose topiramate; Drug: Low dose lamotrigine; Drug: Low dose gabapentin

Standard dose

ACTIVE COMPARATOR

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.

Drug: Standard dose carbamazepine; Drug: Standard dose levetiracetam; Drug: Standard dose valproate; Drug: Standard dose zonisamide; Drug: Standard dose oxcarbazepine; Drug: Standard dose topiramate; Drug: Standard dose lamotrigine; Drug: Standard dose gabapentin

Interventions

Low dose carbamazepine DRUG

Carbamazepine, 300 mg/die

Also known as: low carbamazepine

Low dose

Standard dose carbamazepine DRUG

Carbamazepine 600 mg/die

Also known as: Standard carbamazepine

Standard dose

Low dose levetiracetam DRUG

Levetiracetam 500 mg/die

Also known as: Low levetiracetam

Low dose

Standard dose levetiracetam DRUG

Levetiracetam 1000 mg/die

Also known as: Standard levetiracetam

Standard dose

Low dose valproate DRUG

Valproate 300 mg/die

Also known as: Low valproate

Low dose

Standard dose valproate DRUG

Valproate 600 mg/die

Also known as: Standard valproate

Standard dose

Low dose zonisamide DRUG

Zonisamide 150 mg/die

Also known as: Low zonisamide

Low dose

Standard dose zonisamide DRUG

Zonisamide 300 mg/die

Also known as: Standard zonisamide

Standard dose

Low dose oxcarbazepine DRUG

Oxcarbazepine 600 mg/die

Also known as: Low oxcarbazepine

Low dose

Standard dose oxcarbazepine DRUG

Oxcarbazepine 1200 mg/die

Also known as: Standard oxcarbazepine

Standard dose

Low dose topiramate DRUG

Topiramate 100 mg/die

Also known as: Low topiramate

Low dose

Standard dose topiramate DRUG

Topiramate 200 mg/die

Also known as: Standard topiramate

Standard dose

Low dose lamotrigine DRUG

Lamotrigine 100 mg/die

Also known as: Low lamotrigine

Low dose

Standard dose lamotrigine DRUG

Lamotrigine 200 mg/die

Also known as: Standard lamotrigine

Standard dose

Low dose gabapentin DRUG

Gabapentin 450 mg/die

Also known as: Low gabapentin

Low dose

Standard dose gabapentin DRUG

Gabapentin 900 mg/die

Also known as: Standard gabapentin

Standard dose

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• A patient will be excluded if at least one of the following criteria will be met:
• Age less than 18 years;
• Having experienced primarily or secondarily generalized tonic and/or clonic seizures, or other (non-focal) seizure types;
• Previous exposure to AEDs;
• Requiring low or standard doses on account of individual needs;
• Inability to understand the aims or modalities of the study;
• 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;
• Previous treatment with an antiepileptic drug;
• Men unable to practice contraception for the duration of the treatment.
• Poor compliance with assigned treatments;
• Refusal to release written informed consent;
• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Azienda Ospedaliera San Gerardo di Monza: collaborator
• Ministry of Health, Italy: collaborator

Study Sites (1)

ASST Monza Ospedale San Gerardo

Monza, 20900, Italy

Location

Related Publications (7)

• 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.

  PMID: 21606654 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.

  PMID: 16098770 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.

  PMID: 6790275 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.

  PMID: 24730690 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

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

  PMID: 21429248 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.

  PMID: 21242496 BACKGROUND

MeSH Terms

Conditions

Epilepsies, Partial; Epilepsy

Interventions

Carbamazepine; Levetiracetam; Valproic Acid; Zonisamide; Oxcarbazepine; Topiramate; Lamotrigine; Gabapentin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Fatty Acids; Lipids; Sulfonamides; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Triazines; Amines; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Giorgia Giussani
• Organization: Istituto di Ricerche Farmacologiche Mario Negri IRCCS

giorgia.giussani@marionegri.it

0239014604

Study Officials

• Ettore Beghi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter randomized pragmatic parallel-group single-blind non-inferiority trial.

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: September 28, 2018
• Study Start: May 10, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: July 8, 2025
• Results First Posted: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)