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

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ClinicalTrials.gov Identifier: NCT03689114
Recruitment Status : Not yet recruiting
First Posted : September 28, 2018
Last Update Posted : October 2, 2018
Sponsor:
Collaborators:
Azienda Ospedaliera San Gerardo di Monza
Ministry of Health, Italy
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Tracking Information
First Submitted Date  ICMJE September 27, 2018
First Posted Date  ICMJE September 28, 2018
Last Update Posted Date October 2, 2018
Estimated Study Start Date  ICMJE January 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03689114 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
  • 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;
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
  • 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;
  • Quality of life score [ Time Frame: 12 months ]
    QOLIE-31 total score at the last visit
  • Patients health care's satisfaction [ 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 the last visit
  • Health care resources consuption [ 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low vs. Standard Daily Doses of Antiepileptic Drugs in Newly Diagnosed, Previously Untreated Epilepsy(STANDLOW)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a multicenter randomized pragmatic parallel-group single-blind non-inferiority trial.
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Epilepsies, Partial
Intervention  ICMJE
  • Drug: Low dose carbamazepine
    Carbamazepine, 300 mg/die
    Other Name: low carbamazepine
  • Drug: Standard dose carbamazepine
    Carbamazepine 600 mg/die
    Other Name: Standard carbamazepine
  • Drug: Low dose levetiracetam
    Levetiracetam 500 mg/die
    Other Name: Low levetiracetam
  • Drug: Standard dose levetiracetam
    Levetiracetam 1000 mg/die
    Other Name: Standard levetiracetam
  • Drug: Low dose valproate
    Valproate 300 mg/die
    Other Name: Low valproate
  • Drug: Standard dose valproate
    Valproate 600 mg/die
    Other Name: Standard valproate
  • Drug: Low dose zonisamide
    Zonisamide 150 mg/die
    Other Name: Low zonisamide
  • Drug: Standard dose zonisamide
    Zonisamide 300 mg/die
    Other Name: Standard zonisamide
  • Drug: Low dose oxcarbazepine
    Oxcarbazepine 600 mg/die
    Other Name: Low oxcarbazepine
  • Drug: Standard dose oxcarbazepine
    Oxcarbazepine 1200 mg/die
    Other Name: Standard oxcarbazepine
  • Drug: Low dose topiramate
    Topiramate 100 mg/die
    Other Name: Low topiramate
  • Drug: Standard dose topiramate
    Topiramate 200 mg/die
    Other Name: Standard topiramate
  • Drug: Low dose lamotrigine
    Lamotrigine 100 mg/die
    Other Name: Low lamotrigine
  • Drug: Standard dose lamotrigine
    Lamotrigine 200 mg/die
    Other Name: Standard lamotrigine
  • Drug: Low dose gabapentin
    Gabapentin 450 mg/die
    Other Name: Low gabapentin
  • Drug: Standard dose gabapentin
    Gabapentin 900 mg/die
    Other Name: Standard gabapentin
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Low dose carbamazepine
    • Drug: Low dose levetiracetam
    • Drug: Low dose valproate
    • Drug: Low dose zonisamide
    • Drug: Low dose oxcarbazepine
    • Drug: Low dose topiramate
    • Drug: Low dose lamotrigine
    • Drug: Low dose 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.
    Interventions:
    • Drug: Standard dose carbamazepine
    • Drug: Standard dose levetiracetam
    • Drug: Standard dose valproate
    • Drug: Standard dose zonisamide
    • Drug: Standard dose oxcarbazepine
    • Drug: Standard dose topiramate
    • Drug: Standard dose lamotrigine
    • Drug: Standard dose gabapentin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 27, 2018)
374
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ettore Beghi, MD 0239014542 ettore.beghi@marionegri.it
Contact: Giorgia Giussani, PhD 0239014604 giorgia.giussani@marionegri.it
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03689114
Other Study ID Numbers  ICMJE STANDLOW
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mario Negri Institute for Pharmacological Research
Study Sponsor  ICMJE Mario Negri Institute for Pharmacological Research
Collaborators  ICMJE
  • Azienda Ospedaliera San Gerardo di Monza
  • Ministry of Health, Italy
Investigators  ICMJE
Principal Investigator: Ettore Beghi, MD Istituto di Ricerche Farmacologiche Mario Negri IRCCS
PRS Account Mario Negri Institute for Pharmacological Research
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP