Back to resultsLow vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW) (STANDLOW)
Primary Purpose
Epilepsies, Partial
Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Low dose carbamazepine
Standard dose carbamazepine
Low dose levetiracetam
Standard dose levetiracetam
Low dose valproate
Standard dose valproate
Low dose zonisamide
Standard dose zonisamide
Low dose oxcarbazepine
Standard dose oxcarbazepine
Low dose topiramate
Standard dose topiramate
Low dose lamotrigine
Standard dose lamotrigine
Low dose gabapentin
Standard dose gabapentin
Sponsored by
About this trial
This is an interventional treatment trial for Epilepsies, Partial focused on measuring epilepsy, antiepileptic drugs, low dose, standard dose, new diagnosis
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Low dose
Standard dose
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Drug-related adverse events
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
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
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.
The mean daily patient's cost of health care resources consumed for the management of epilepsy during the first 12 months of the study.
Full Information
NCT ID
NCT03689114
First Posted
September 27, 2018
Last Updated
September 25, 2019
Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
Azienda Ospedaliera San Gerardo di Monza, Ministry of Health, Italy
1. Study Identification
Unique Protocol Identification Number
NCT03689114
Brief Title
Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW)
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 7, 2020 (Anticipated)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
Azienda Ospedaliera San Gerardo di Monza, Ministry of Health, Italy
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsies, Partial
Keywords
epilepsy, antiepileptic drugs, low dose, standard dose, new diagnosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
This is a multicenter randomized pragmatic parallel-group single-blind non-inferiority trial.
Masking
Participant
Allocation
Randomized
Enrollment
374 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low dose
Arm Type
Experimental
Arm 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.
Arm Title
Standard dose
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Low dose carbamazepine
Other Intervention Name(s)
low carbamazepine
Intervention Description
Carbamazepine, 300 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose carbamazepine
Other Intervention Name(s)
Standard carbamazepine
Intervention Description
Carbamazepine 600 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose levetiracetam
Other Intervention Name(s)
Low levetiracetam
Intervention Description
Levetiracetam 500 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose levetiracetam
Other Intervention Name(s)
Standard levetiracetam
Intervention Description
Levetiracetam 1000 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose valproate
Other Intervention Name(s)
Low valproate
Intervention Description
Valproate 300 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose valproate
Other Intervention Name(s)
Standard valproate
Intervention Description
Valproate 600 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose zonisamide
Other Intervention Name(s)
Low zonisamide
Intervention Description
Zonisamide 150 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose zonisamide
Other Intervention Name(s)
Standard zonisamide
Intervention Description
Zonisamide 300 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose oxcarbazepine
Other Intervention Name(s)
Low oxcarbazepine
Intervention Description
Oxcarbazepine 600 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose oxcarbazepine
Other Intervention Name(s)
Standard oxcarbazepine
Intervention Description
Oxcarbazepine 1200 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose topiramate
Other Intervention Name(s)
Low topiramate
Intervention Description
Topiramate 100 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose topiramate
Other Intervention Name(s)
Standard topiramate
Intervention Description
Topiramate 200 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose lamotrigine
Other Intervention Name(s)
Low lamotrigine
Intervention Description
Lamotrigine 100 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose lamotrigine
Other Intervention Name(s)
Standard lamotrigine
Intervention Description
Lamotrigine 200 mg/die
Intervention Type
Drug
Intervention Name(s)
Low dose gabapentin
Other Intervention Name(s)
Low gabapentin
Intervention Description
Gabapentin 450 mg/die
Intervention Type
Drug
Intervention Name(s)
Standard dose gabapentin
Other Intervention Name(s)
Standard gabapentin
Intervention Description
Gabapentin 900 mg/die
Primary Outcome Measure Information:
Title
Treatment failure
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Drug-related adverse events
Description
the proportion of patients experiencing a treatment failure motivated by intolerable drug-related adverse events during the follow-up;
Time Frame
12 months
Title
Quality of life in epilepsy scale 31 items(QOLIE-31), italian version
Description
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).
Time Frame
12 months
Title
Patients health care's satisfaction (PSQ-18) scale, 18 items
Description
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.
Time Frame
12 months
Title
Health care resources utilization.
Description
The mean daily patient's cost of health care resources consumed for the management of epilepsy during the first 12 months of the study.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ettore Beghi, MD
Phone
0239014542
Email
ettore.beghi@marionegri.it
First Name & Middle Initial & Last Name or Official Title & Degree
Giorgia Giussani, PhD
Phone
0239014604
Email
giorgia.giussani@marionegri.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ettore Beghi, MD
Organizational Affiliation
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21606654
Citation
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.
Results Reference
background
PubMed Identifier
16098770
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.
Results Reference
background
PubMed Identifier
6790275
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.
Results Reference
background
PubMed Identifier
24730690
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.
Results Reference
background
PubMed Identifier
11971128
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.
Results Reference
background
PubMed Identifier
21429248
Citation
Maguire M, Marson AG, Ramaratnam S. Epilepsy (partial). BMJ Clin Evid. 2010 Jun 28;2010:1214.
Results Reference
background
PubMed Identifier
21242496
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.
Results Reference
background
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Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW)
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