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

March 11, 2024 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

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

374

Phase

  • 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 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

Ages Eligible for Study

16 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
Intervention / Treatment
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

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.
12 months

Secondary Outcome Measures

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
Quality of life in epilepsy scale 31 items(QOLIE-31), italian version
Time Frame: 12 months
QOLIE-31 total score at baseline and last visit. Maximum total score is 100 (best quality of life possible) and the minimum is 0 (worst quality of life possible).
12 months
Patients health care's satisfaction (PSQ-18) scale, 18 items
Time Frame: 12 months
The score of the seven PSQ-18 subscales (general satisfaction, technical quality, interpersonal manner, communication, financial aspects, time spent with doctor, accessibility and convenience) at baseline and last visit. Possible scores of each subscale range from 1 (worst satisfaction) to 5 (better satisfaction). There is no total score for this scale.
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

Mario Negri Institute for Pharmacological Research

Collaborators

Ministry of Health, Italy
Azienda Ospedaliera San Gerardo di Monza

Investigators

  • Principal Investigator: Ettore Beghi, MD, Istituto di Ricerche Farmacologiche Mario Negri IRCCS

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)

May 10, 2021

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

September 27, 2018

First Submitted That Met QC Criteria

September 27, 2018

First Posted (Actual)

September 28, 2018

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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