Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures

• Sponsor: Mazandaran University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT03940326
• Collaborator: (none)
• Enrollment: 103
• Location: 1
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

This study is an open-label, active-controlled,non-inferiority trial comparing efficacy and safety of levetiracetam versus valproate in idiopathic generalized tonic-clonic epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy, Idiopathic Generalized	Drug: Levetiracetam; Drug: Valproate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison Study of Efficacy and Safety of Levetiracetam Versus Valproate in Treatment of Idiopathic Generalized Tonic-clonic Seizures
• Actual Study Start Date: Apr 1, 2018
• Actual Primary Completion Date: Oct 1, 2019
• Actual Study Completion Date: Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Levetiracetam	Drug: Levetiracetam; Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred; Other Names: Levebel
Active Comparator: Valproate	Drug: Valproate; Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.

Outcome Measures

Primary Outcome Measures

1. Time to First Seizure [6 months]

   The time interval from the beginning of the study to occurrence of the first seizure

2. Seizure Freedom Rate [6 months]

Secondary Outcome Measures

1. Withdrawal Rate [6 months]

2. Time to Withdrawal [9 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age≥16

• At least 2 unprovoked generalized tonic-clonic seizures in last 2 years with at least one in last 6 months

• Normal brain MRI or MRI without epileptogenic lesion

• Normal electroencephalography(EEG) or existence of generalized epileptiform discharges without any focal epileptiform discharges.

• Signing consent form

Exclusion Criteria:

• History of treatment by sodium valproate or levetiracetam

• History of treatment by any anti-epileptic drug in last 6 months

• Plan for pregnancy

• Using no certain contraceptive method

• History of past or current hepatic disease

• History of past or current renal disease

• History of past or current hematologic disease

• History of known psychiatric disease

• History of status epilepticus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bu Ali Sina Hospital	Sari	Mazandaran	Iran, Islamic Republic of	4815837477

Sponsors and Collaborators

• Mazandaran University of Medical Sciences

Investigators

• Principal Investigator: Nasim Tabrizi, MD, Neurology department, Mazandaran University of Medical Sciences, Sari, Iran.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 8, 2020

More Information

Publications

None provided.

• Responsible Party: Nasim Tabrizi, Assistant professor of neurology, Mazandaran University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT03940326
• Other Study ID Numbers: LEVIGS
• First Posted: May 7, 2019
• Last Update Posted: Feb 17, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Seizures; Levetiracetam; Valproic Acid

Study Results

Participant Flow

Arm/Group Title	Levetiracetam	Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
Period Title: Overall Study
STARTED	45	58
COMPLETED	45	58
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Levetiracetam	Valproate	Total
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.	Total of all reporting groups
Overall Participants	45	58	103
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	45 100%	58 100%	103 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.2 (8.1)	29 (9.7)	27.7 (9.1)
Sex: Female, Male (Count of Participants)
Female	32 71.1%	17 29.3%	49 47.6%
Male	13 28.9%	41 70.7%	54 52.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	45 100%	58 100%	103 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Iran	45 100%	58 100%	103 100%

Outcome Measures

1. Primary Outcome

Title	Time to First Seizure
Description	The time interval from the beginning of the study to occurrence of the first seizure
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam	Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
Measure Participants	45	58
Mean (Standard Deviation) [Days]	169 (6.1)	178 (2.2)

2. Primary Outcome

Title	Seizure Freedom Rate
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam	Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
Measure Participants	45	58
Count of Participants [Participants]	40 88.9%	50 86.2%

3. Secondary Outcome

Title	Withdrawal Rate
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam	Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
Measure Participants	45	58
Count of Participants [Participants]	4 8.9%	6 10.3%

4. Secondary Outcome

Title	Time to Withdrawal
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levetiracetam	Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred	Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
Measure Participants	45	58
Mean (Standard Deviation) [Days]	220 (8.7)	172 (4.1)

Adverse Events

Time Frame	6 months
Arm/Group Title	Levetiracetam		Valproate
Arm/Group Description	Levetiracetam: Levetiracetam with initial dose of 500 mg per 12 hours which will be increased 500 mg/week to target dose of 2000 mg/day and the dose could be increased to 3000 mg/day if seizures recurred		Valproate: Sodium valproate with initial dose of 500 mg/day which will be increased 500 mg/week to target dose of 1500 mg/day and the dose could be increased to 2000 mg/d if seizures recurred.
All Cause Mortality
	Levetiracetam		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/58 (0%)
Serious Adverse Events
	Levetiracetam		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		2/58 (3.4%)
Hepatobiliary disorders
Rise in liver enzymes	0/45 (0%)	0	2/58 (3.4%)	2
Other (Not Including Serious) Adverse Events
	Levetiracetam		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/45 (37.8%)		30/58 (51.7%)
Endocrine disorders
Weight gain	0/45 (0%)	0	16/58 (27.6%)	16
Irregularity of menstrual period	0/45 (0%)	0	1/58 (1.7%)	1
Gastrointestinal disorders
Dyspepsia	0/45 (0%)	0	6/58 (10.3%)	6
General disorders
Tiredness	1/45 (2.2%)	1	2/58 (3.4%)	2
Abnormal laboratory findings	0/45 (0%)	0	2/58 (3.4%)	2
Nervous system disorders
Somnolence	3/45 (6.7%)	3	3/58 (5.2%)	3
Tremor	0/45 (0%)	0	1/58 (1.7%)	1
Dizziness/vertigo	6/45 (13.3%)	6	1/58 (1.7%)	1
Psychiatric symptoms	9/45 (20%)	9	0/58 (0%)	0
Skin and subcutaneous tissue disorders
Hair loss	0/45 (0%)	0	1/58 (1.7%)	1

Limitations/Caveats

The decision to choose between two arms of the study was made based on clinicians' judgment and we could not randomized or blind the study. The current results are based on a 6-month follow up of patients and the results in longer follow up periods might be different. The low number of patients might decrease the power of this study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.