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

Epilepsies, Partial Clinical Trial

— STANDLOW  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03689114
• Other study ID #: STANDLOW
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: May 10, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: March 2024
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 374
• Est. completion date: August 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy

Intervention

Drug:
• Low dose carbamazepine
Carbamazepine, 300 mg/die
• Standard dose carbamazepine
Carbamazepine 600 mg/die
• Low dose levetiracetam
Levetiracetam 500 mg/die
• Standard dose levetiracetam
Levetiracetam 1000 mg/die
• Low dose valproate
Valproate 300 mg/die
• Standard dose valproate
Valproate 600 mg/die
• Low dose zonisamide
Zonisamide 150 mg/die
• Standard dose zonisamide
Zonisamide 300 mg/die
• Low dose oxcarbazepine
Oxcarbazepine 600 mg/die
• Standard dose oxcarbazepine
Oxcarbazepine 1200 mg/die
• Low dose topiramate
Topiramate 100 mg/die
• Standard dose topiramate
Topiramate 200 mg/die
• Low dose lamotrigine
Lamotrigine 100 mg/die
• Standard dose lamotrigine
Lamotrigine 200 mg/die
• Low dose gabapentin
Gabapentin 450 mg/die
• Standard dose gabapentin
Gabapentin 900 mg/die

Locations

Country	Name	City	State
Italy	ASST Monza Ospedale San Gerardo	Monza

Sponsors (3)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	Azienda Ospedaliera San Gerardo di Monza, Ministry of Health, Italy

Country where clinical trial is conducted

Italy, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

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