NCT03048084

Brief Summary

Currently, treatment with a specific anti-epileptic drug mainly depends on the physicians' preference, as there are no studies supporting the use of one specific anticonvulsant in glioma patients. The overall aim of this randomized controlled trial is to directly compare the effectiveness of treatment with levetiracetam or valproic acid in glioma patients with a first seizure.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_4

Timeline
26mo left

Started Feb 2018

Longer than P75 for phase_4

Geographic Reach
1 country

5 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Feb 2018Jul 2028

First Submitted

Initial submission to the registry

February 7, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 9, 2017

Completed
12 months until next milestone

Study Start

First participant enrolled

February 1, 2018

Completed
8.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

February 4, 2025

Status Verified

January 1, 2025

Enrollment Period

8.4 years

First QC Date

February 7, 2017

Last Update Submit

January 31, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Ongoing seizure freedom at 6 months

    The percentage of patients with ongoing seizure freedom at 6 months

    6 months

Secondary Outcomes (12)

  • Time to 6 months seizure freedom

    0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively

  • Seizure outcome at 12 months

    12 months

  • Adverse effects of the treatment

    0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively

  • Hospitalisation rate

    0, 1, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 1, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively

  • Health-related quality of life

    0, 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months or 0, 6, 12, 18, 24 and 30 months, depending on a 3-monthly or 6-monthly follow-up schedule respectively

  • +7 more secondary outcomes

Study Arms (2)

Levetiracetam

ACTIVE COMPARATOR

Patients in this treatment arm will receive levetiracetam monotherapy. The dosage depends on the specific treatment step, as indicated in the protocol. In step 1, patients will receive 2x500 mg/d levetiracetam in the form of tablets. In step 2, dosage is increased to 1x250 plus 1x500 mg/d and in step 3 to 2x1000 mg/d levetiracetam. In step 4, levetiracetam is increased to 2x1500mg/d. In the fifth treatment step, patients will receive 2x1500 mg/d levetiracetam, and another AED will be added. The type and dosage of this add-on AED is according to the physician's preference, but in line with current clinical practice in the Netherlands.

Drug: Levetiracetam

Valproic acid

ACTIVE COMPARATOR

Patients in this treatment arm will receive valproic acid monotherapy. The dosage depends on the specific treatment step, as indicated in the protocol. In step 1, patients will receive 2x500 mg/d valproic acid in the form of tablets. In step 2, dosage is increased to 1x250 plus 1x500 mg/d and in step 3 to 2x1000 mg/d valproic acid. In step 4, valproic acid dosage is increased to a maximum of 2x1250mg/d. In the fifth treatment step, patients will receive 2x1250mg valproic acid, and another AED will be added. The type and dosage of this add-on AED is according to the physician's preference, but in line with current clinical practice in the Netherlands.

Drug: Valproic Acid

Interventions

Antiepileptic drug levetiracetam

Also known as: Keppra
Levetiracetam

Antiepileptic drug valproic acid

Also known as: Depakine
Valproic acid

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically proven or suspected diffuse astrocytoma (Isocytrate Dehydrogenase-1 (IDH-1) wildtype or IDH-1 mutated), diffuse oligodendroglioma (IDH-1 mutated and 1p/19q co-deleted), anaplastic astrocytoma (IDH-1 wildtype or IDH-1 mutated), anaplastic oligodendroglioma (IDH-1 mutated and 1p/19q co-deleted), glioblastoma (IDH-1 wild-type or IDH-1 mutated), or diffuse astrocytoma not otherwise specified (NOS), anaplastic astrocytoma NOS, oligodendroglioma NOS, oligoastrocytoma NOS, anaplastic oligoastrocytoma NOS, anaplastic oligodendroglioma NOS or glioblastoma NOS.
  • Adult patients: ≥18 years of age
  • First epileptic seizure, no longer than 2 weeks ago
  • Monotherapy with antiepileptic drugs is considered most appropriate at the time of randomization
  • Willing to provide written informed consent

You may not qualify if:

  • Previously treated with antiepileptic drugs, except emergency treatment in the past 2 weeks
  • History of non-brain tumor related epilepsy
  • Pregnancy
  • Presence of contra-indications for use of levetiracetam or valproic acid

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Amsterdam UMC

Amsterdam, 1007 MB, Netherlands

SUSPENDED

Medisch Spectrum Twente

Enschede, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, 3008 AE, Netherlands

RECRUITING

Haaglanden Medical Center

The Hague, 2501 CK, Netherlands

RECRUITING

Related Publications (2)

  • van der Meer PB, Taphoorn MJB, Koekkoek JAF. Management of epilepsy in brain tumor patients. Curr Opin Oncol. 2022 Nov 1;34(6):685-690. doi: 10.1097/CCO.0000000000000876. Epub 2022 Jul 16.

  • Lang F, Liu Y, Chou FJ, Yang C. Genotoxic therapy and resistance mechanism in gliomas. Pharmacol Ther. 2021 Dec;228:107922. doi: 10.1016/j.pharmthera.2021.107922. Epub 2021 Jun 23.

MeSH Terms

Conditions

Glioma

Interventions

LevetiracetamValproic Acid

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

AcetamidesAmidesOrganic ChemicalsAcetatesAcids, AcyclicCarboxylic AcidsPyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPentanoic AcidsValeratesFatty Acids, VolatileFatty AcidsLipids

Central Study Contacts

Johan AF Koekkoek, MD, PhD

CONTACT

Monique Baas

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

February 7, 2017

First Posted

February 9, 2017

Study Start

February 1, 2018

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2028

Last Updated

February 4, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations