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

July 7, 2025 updated by: Mario Negri Institute for Pharmacological Research

Efficacy and Tolerability of Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy (STANDLOW). A Multicenter, Randomized, Single-blind, Parallel-group Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
58

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Monza, Italy, 20900
        • ASST Monza Ospedale San Gerardo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Low dose carbamazepine
Carbamazepine, 300 mg/die
Other Names:
  • low carbamazepine
Drug: Low dose levetiracetam
Levetiracetam 500 mg/die
Other Names:
  • Low levetiracetam
Drug: Low dose valproate
Valproate 300 mg/die
Other Names:
  • Low valproate
Drug: Low dose zonisamide
Zonisamide 150 mg/die
Other Names:
  • Low zonisamide
Drug: Low dose oxcarbazepine
Oxcarbazepine 600 mg/die
Other Names:
  • Low oxcarbazepine
Drug: Low dose topiramate
Topiramate 100 mg/die
Other Names:
  • Low topiramate
Drug: Low dose lamotrigine
Lamotrigine 100 mg/die
Other Names:
  • Low lamotrigine
Drug: Low dose gabapentin
Gabapentin 450 mg/die
Other Names:
  • Low gabapentin
Active Comparator: 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.
Drug: Standard dose carbamazepine
Carbamazepine 600 mg/die
Other Names:
  • Standard carbamazepine
Drug: Standard dose levetiracetam
Levetiracetam 1000 mg/die
Other Names:
  • Standard levetiracetam
Drug: Standard dose valproate
Valproate 600 mg/die
Other Names:
  • Standard valproate
Drug: Standard dose zonisamide
Zonisamide 300 mg/die
Other Names:
  • Standard zonisamide
Drug: Standard dose oxcarbazepine
Oxcarbazepine 1200 mg/die
Other Names:
  • Standard oxcarbazepine
Drug: Standard dose topiramate
Topiramate 200 mg/die
Other Names:
  • Standard topiramate
Drug: Standard dose lamotrigine
Lamotrigine 200 mg/die
Other Names:
  • Standard lamotrigine
Drug: Standard dose gabapentin
Gabapentin 900 mg/die
Other Names:
  • Standard gabapentin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Treatment Failure
Time Frame: 12 months

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Drug-related Adverse Events
Time Frame: 12 months
the proportion of patients experiencing a treatment failure motivated by intolerable drug-related adverse events during the follow-up;
12 months
PSQ-18, Italian Version
Time Frame: 12 months
The score of the seven Patients Satisfaction Questionnaire 18 items (PSQ-18) subscales (general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with doctor, accessibility and convenience) at the last visit; the score of each subscale ranges from 1 (worst) to 5 (best).
12 months
QoLIE-31, Italian Version
Time Frame: 12 months
QoLIE-31 measures the quality of life of patients with epilepsy (range 0-100, where 0 corresponds to the worst quality of life and 100 corresponds to the best), at the end of study visit.
12 months
Health Care Resources Utilization.
Time Frame: 12 months
The mean daily patient's cost of health care resources consumed for the management of epilepsy during the first 12 months of the study.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mario Negri Institute for Pharmacological Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ministry of Health, Italy
Azienda Ospedaliera San Gerardo di Monza

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ettore Beghi, MD, Istituto Di Ricerche Farmacologiche Mario Negri

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 10, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STANDLOW

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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