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

Sponsor

Mario Negri Institute for Pharmacological Research (Other)

Overall Status

Unknown status

CT.gov ID

NCT03689114

Collaborator

Azienda Ospedaliera San Gerardo di Monza (Other), Ministry of Health, Italy (Other)

374

Enrollment

Arms

22.8

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: Low dose carbamazepine Drug: Standard dose carbamazepine Drug: Low dose levetiracetam Drug: Standard dose levetiracetam Drug: Low dose valproate Drug: Standard dose valproate Drug: Low dose zonisamide Drug: Standard dose zonisamide Drug: Low dose oxcarbazepine Drug: Standard dose oxcarbazepine Drug: Low dose topiramate Drug: Standard dose topiramate Drug: Low dose lamotrigine Drug: Standard dose lamotrigine Drug: Low dose gabapentin Drug: Standard dose gabapentin	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

374 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 7, 2020

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Treatment failure [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.

Secondary Outcome Measures

Drug-related adverse events [12 months]
the proportion of patients experiencing a treatment failure motivated by intolerable drug-related adverse events during the follow-up;
Quality of life in epilepsy scale 31 items(QOLIE-31), italian version [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).
Patients health care's satisfaction (PSQ-18) scale, 18 items [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.
Health care resources utilization. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.