Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures

This study has been terminated.
(Insufficient enrollment)
Sponsor:
Information provided by (Responsible Party):
Cyberonics, Inc.
ClinicalTrials.gov Identifier:
NCT01118455
First received: May 5, 2010
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

This is a randomized study designed to compare long-term treatment outcomes in pediatric patients with refractory seizures treated with VNS (Vagus Nerve Stimulation) Therapy versus anti-epileptic drugs (AEDs). Seizure reduction, quality of life measures, and side effect profiles will be evaluated. The results of this study will provide controlled comparative data to better guide physicians in determining the best overall treatment strategy for patients with seizures who have failed initial AED therapy.


Condition Intervention Phase
Epilepsy
Device: Vagus Nerve Stimulation (VNS) Therapy
Drug: Anti-Epileptic Drug (AED)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Randomized Trial to Assess the Efficacy and Safety of Vagus Nerve Stimulation (VNS) Versus New Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures

Resource links provided by NLM:


Further study details as provided by Cyberonics, Inc.:

Primary Outcome Measures:
  • Proportion of Responders After 1 Year of Follow-up (ITT-population) [ Time Frame: 52 weeks post baseline ] [ Designated as safety issue: No ]
    Responders are subjects who had no new AEDs added or significant dose changes in baseline AEDs within 1 year of follow-up, along with a reduction in the percentage change in seizure frequency from baseline to the 2-month period prior to the 1-year follow-up of at least 50%.


Secondary Outcome Measures:
  • Mean Percent Change in Hague Seizure Severity Scale Score (ITT Population) [ Time Frame: 52 weeks post baseline ] [ Designated as safety issue: No ]
    The Hague Seizure Severity Assessment (Carpay et al. 1996) is a scale completed by the patient and/or caregiver to assess the severity and post-ictal recovery of seizures. A reduction in the HSSA score reflects less seizure severity experienced.

  • Wellcome Quality of Life Assessment (Questionnaire A) in Epilepsy (ITT Population) [ Time Frame: 52 weeks post baseline ] [ Designated as safety issue: No ]

    Calculate changes in the Wellcome Quality of Life Assessment (Parker et al. 1999) (Questionnaire A) for patients in both treatment arms (AED and VNS) at 52 weeks after randomization compared to baseline. The higher the quality of life score the better the quality of life experienced.

    An analysis of variance (ANOVA) model will be used to adjust for baseline variables (including QoL score) when comparing the two treatment groups. A two-sample t-test will be used for simple comparison QoL change from baseline.

    Total range for this scale is a minimum score of 81 to a maximum score of 336. There are no applicable subscales.


  • Hague Restriction in Childhood Epilepsy Scale (Questionnaire B) (ITT Population) [ Time Frame: 52 weeks post baseline ] [ Designated as safety issue: No ]

    Calculate changes in the Hague Restriction in Childhood Epilepsy scale (Carpay et al. 1997) (Questionnaire B) for patients in both treatment arms (AED and VNS) at 52 weeks after randomization compared to baseline. The higher the quality of life score the better the quality of life experienced.

    An analysis of variance (ANOVA) model will be used to adjust for baseline variables (including QoL score) when comparing the two treatment groups. A two-sample t-test will be used for simple comparison QoL change from baseline.

    Total range for this scale is a minimum score of 10 to a maximum score of 40. There are no applicable subscales.


  • Mean Percent Change in Seizure Frequency (ITT Population) [ Time Frame: 52 weeks post baseline ] [ Designated as safety issue: No ]

    The mean percent change in seizure frequency for the VNS and AED treatment groups at 52 weeks post baseline.

    Both AED and VNS treatment groups were stratified according to the patients' number of previous AED treatments ("early group" had 2 to 5 AEDs tested to tolerance or to blood levels at upper end of target range; "non-early group" had more than 5 AEDs tested to tolerance or to blood levels at upper end of target range). Seizure frequency was calculated based on number of patient/caregiver reported seizures at 52-week post baseline (percentage change in seizure frequency from baseline to the 2-month period prior to the 1-year follow-up of at least 50%). All seizures were counted.

    The safety population consists of 66 VNS implanted patients and the AED safety population includes 69 patients who are randomized to the AED arm.

    Please note one patient in the VNS safety population who was implanted but never received stimulation was excluded from the ITT population.


  • Number of Subjects With Any Non-Serious Adverse Events by System Organ Class and Preferred Term (Safety Population) [ Time Frame: 0-52 weeks ] [ Designated as safety issue: Yes ]

    To compare the safety of Vagus Nerve Stimulation (VNS) treatment using the VNS Therapy device to anti-epileptic drug (AED) therapy in treating patients with seizures.

    The safety population consists of 66 VNS implanted patients and the AED safety population includes 69 patients who are randomized to the AED arm.

    Please note one patient in the VNS safety population who was implanted but never received stimulation was excluded from the ITT population.


  • Number of Subjects With Any Serious Adverse Events by System Organ Class & Preferred Term (Safety Population) [ Time Frame: 0-52 weeks ] [ Designated as safety issue: Yes ]

    To compare the safety of Vagus Nerve Stimulation (VNS) treatment using the VNS Therapy device to anti-epileptic drug (AED) therapy in treating patients with seizures.

    The safety population consists of 66 VNS implanted patients and the AED safety population includes 69 patients who are randomized to the AED arm.

    Please note one patient in the VNS safety population who was implanted but never received stimulation was excluded from the ITT population.



Enrollment: 134
Study Start Date: October 2004
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vagus Nerve Stimulation (VNS) Therapy
Vagus Nerve Stimulation (VNS) Therapy is delivered by an implantable device similar to a pacemaker that sends mild stimulation to the left vagus nerve to help improve seizure control.
Device: Vagus Nerve Stimulation (VNS) Therapy
Vagus Nerve Stimulation (VNS) Therapy is delivered by an implantable device similar to a pacemaker that sends mild stimulation to the left vagus nerve to help improve seizure control.
Other Name: Vagus Nerve Stimulation (VNS) Therapy
Experimental: Anti-Epileptic Drug (AED)
This arm will supply a comparison between VNS and new AEDs which is necessary to determine an overall treatment regimen for the 30% to 40% of patients who fail to respond to 2 AEDs.
Drug: Anti-Epileptic Drug (AED)
Subject has tried at least 2 appropriate AEDs tested to tolerance or to blood levels at upper end of the target range of which at least 2 had been tolerated at normal doses.
Other Name: Anti-Epileptic Drug (AED)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Refractory seizures
  2. Having tried at least two appropriate anti-epileptic drugs (AEDs) tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal dose;
  3. Having at least 3 appropriate AEDs left to try
  4. Having his/her current AED medication at an optimal dose at baseline
  5. At least three seizures per month (average over 2 months prior to admission), excluding absences.
  6. No more than four (4) weeks between seizures (over 2 months prior to admission)
  7. Age 17 years or less
  8. Having been evaluated for epilepsy surgery and resective surgery not felt indicated or patient/parents/legal guardian declined.
  9. Patient is a male or patient is a nonpregnant female adequately protected from conception. Females of childbearing potential must use an acceptable method of birth control. Abstinence is an acceptable means of birth control
  10. Patient or legal guardian understands study procedures and has voluntarily signed an informed consent in accordance with institutional policies.

Exclusion Criteria:

  1. Having tried less then 2 AEDs tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal doses in the patient's lifetime
  2. A progressive neurological condition (e.g. brain tumor etc.)
  3. Inability of the parents or reluctance of the child to comply with the frequency of clinic visits during the treatment phase
  4. Patient has a history of noncompliance for seizure diary completion.
  5. Patient has taken an investigational drug within a period of five times the mean elimination half-life of the investigational drug plus two weeks.
  6. Patient is currently using another investigational device or drug.
  7. Patient is likely to require a whole body Magnetic resonance imaging (MRI) after VNS Therapy device implantation. (Refer to the Physician's Manual for the NCP Generator for additional information on the use of MRI.)
  8. Patient is currently receiving or likely to receive short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy after implantation (Refer to Physician's Manual for the VNS (Vagus Nerve Stimulation) Therapy device for additional information on the contraindicated use of diathermy).
  9. Patient was previously enrolled in this or any other VNS Therapy device Study.
  10. Patient has an active peptic ulcer
  11. Patient has another unstable medical condition likely to precipitate seizures and make it difficult to evaluate to evaluate efficacy (e.g. diabetes)
  12. Patient has had a unilateral or bilateral cervical vagotomy.
  13. Patient is pregnant at the time of enrolment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118455

Locations
Austria
Medical University of Vienna - Vienna General Hospital (AKH)
Vienna, Austria
Belgium
ULB- Hospital Erasme
Brussels, Belgium
Germany
Kinderklinik der Justus-Liebig Universität
Giessen, Germany
University Children's Hospital
Lübeck, Germany
Sweden
University Hospital Lund
Lund, Sweden
Astrid Lindgrens Barnsjukhus Karolinska
Stockholm, Sweden
Uppsala University Hospital
Uppsala, Sweden
United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom
Royal Hospital for Sick Children
Bristol, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
Ninewells Hospital & Medical School
Dundee, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
Great Ormond Street Hospital for Children
London, United Kingdom
King's College Hospital
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom
Sir James Spence Institute - Royal Victoria Infirmary
Newcastle, United Kingdom
Queens's Medical Centre Nottingham
Nottingham, United Kingdom
Sheffield Children's Hospital
Sheffield, United Kingdom
Southampton Hospital
Southampton, United Kingdom
Sponsors and Collaborators
Cyberonics, Inc.
Investigators
Study Director: Mark Bunker, PharmD Cyberonics, Inc.
  More Information

No publications provided

Responsible Party: Cyberonics, Inc.
ClinicalTrials.gov Identifier: NCT01118455     History of Changes
Other Study ID Numbers: Epilepsy (E)-06
Study First Received: May 5, 2010
Results First Received: March 1, 2011
Last Updated: June 25, 2014
Health Authority: United Kingdom: Research Ethics Committee
Belgium: Institutional Review Board
Sweden: Institutional Review Board
Germany: Ethics Commission
Austria: Ethikkommission

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014