Multicentre Study on Rapid Versus Slow Withdrawal of Antiepileptic Monotherapy (RASLOW)

Rapid Versus Slow Withdrawal of Antiepileptic Monotherapy in 2-year Seizure-free Adult Patients With Epilepsy (RASLOW) Study: a Pragmatic Multicentre, Prospective, Randomized, Controlled Study

The main objective of the present study will be to establish whether a slow (within 160 days) or a rapid (within 60 days) withdrawal schedule of antiepileptic monotherapy influence relapse rate in adult patients with epilepsy, who have been seizure free for at least 2 years. Secondary objectives will be to establish the compliance rates with these two schedules and the differences in terms of severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries and death.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Rapid withdrawal of antiepileptic; Drug: Slow withdrawal of antiepileptic

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Reggio Calabria, Italy, 89100
    • Regional Epilepsy Center, Presidio Riuniti, Magna Græcia University of Catanzaro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of focal or generalized epilepsy (according to International League Against Epilepsy 1989 criteria)
• age at epilepsy onset of 16 years or older
• seizure freedom for at least 2 years
• treatment with one of the antiepilepsy drugs currently available for monotherapy in Italy: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproic acid zonisamide)
• adherence to the protocol and visit schedules.

Exclusion Criteria:

• inability to understand the aims or modalities of the study;
• current pregnancy or plans to become pregnant during withdrawal period;
• history of seizure relapse after discontinuation of treatment;
• history of psychogenic non-epileptic seizures (PNES);
• history of status epilepticus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Rapid withdrawal; Reduction by about 20 % of initial dosage every 15 days until complete discontinuation (total withdrawal time: 60 days).	Drug: Rapid withdrawal of antiepileptic; Reduction by about 20 % of initial dosage every 15 days until complete discontinuation (total withdrawal time: 60 days). Drugs: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproic acid, zonisamide; Other Names: antiepileptic
Other: Slow withdrawal; Reduction by about 20 % of initial dosage every 40 days, until complete discontinuation (total withdrawal time: 160 days).	Drug: Slow withdrawal of antiepileptic; Slow withdrawal: reduction by about 20 % of initial dosage every 40 days, until complete discontinuation (total withdrawal time: 160 days). Drugs: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproic acid, zonisamide; Other Names: antiepileptic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to seizure relapse	Time to recurrence of an epileptic seizure, assesed by telephone call and outpatients visits.	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' compliance with the assigned withdrawal schedule	Compliance with the assigned withdrawal schedule (evaluated by telephone interview) and outpatients visits.	365 days
Severity of relapses and mortality	Severity of relapses, in terms of seizure-related injuries, status epilepticus (SE) during or after withdrawal period, and mortality	365 days

Collaborators and Investigators

• Sponsor: University Magna Graecia
• Collaborators: Ministry of Health, Italy

Publications and helpful links

General Publications

• Del Felice A, Beghi E, Boero G, La Neve A, Bogliun G, De Palo A, Specchio LM. Early versus late remission in a cohort of patients with newly diagnosed epilepsy. Epilepsia. 2010 Jan;51(1):37-42. doi: 10.1111/j.1528-1167.2009.02141.x. Epub 2009 Jun 1.
• Ranganathan LN, Ramaratnam S. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005003. doi: 10.1002/14651858.CD005003.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2017
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: January 18, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Anticonvulsants
• Other Study ID Numbers: GR-2013-02358677

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No