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

Mario Negri Institute for Pharmacological Research

Status and phase: Completed; Phase 4

Conditions: Epilepsies, Partial

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03689114

STANDLOW

Details and patient eligibility

About

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.

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

58 participants in 2 patient groups

Low dose

Experimental group

Description:

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.

Treatment:

Drug: Low dose zonisamide

Drug: Low dose oxcarbazepine

Drug: Low dose valproate

Drug: Low dose lamotrigine

Drug: Low dose topiramate

Drug: Low dose carbamazepine

Drug: Low dose levetiracetam

Drug: Low dose gabapentin

Standard dose

Active Comparator group

Description:

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.

Treatment:

Drug: Standard dose oxcarbazepine

Drug: Standard dose levetiracetam

Drug: Standard dose lamotrigine

Drug: Standard dose zonisamide

Drug: Standard dose valproate

Drug: Standard dose topiramate

Drug: Standard dose carbamazepine

Drug: Standard dose gabapentin