ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12606000102572

Ethics application status

Approved

Date submitted

16/03/2006

Date registered

16/03/2006

Date last updated

16/03/2006

Type of registration

Retrospectively registered

Titles & IDs

Public title

Neuropsychiatric, Neurocognitive And Quality Of Life Outcomes In Patients With Epilepsy Treated With Levetiracetam (Keppra) Verses Older AEDs As First Substitution Monotherapy.

Scientific title

Neuropsychiatric, Neurocognitive And Quality Of Life Outcomes In Patients With Epilepsy Treated With Levetiracetam (Keppra) Verses Older AEDs As First Substitution Monotherapy.

Universal Trial Number (UTN)

Trial acronym

KONQUEST: Keppra versus Older AEDs and Neuropsychiatric, Neurocognitive and QUality of life outcomes in treatment of Epilepsy as first Substitution monoTherapy.

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Epilepsy

Condition category

Condition code

Neurological

Epilepsy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Keppra will be used in those who failed their first antiepileptic drug either because of side effects or because of lack of efficacy. Enrolment will take place over 52 weeks and total duration of the study is 2 years.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Older antiepileptic drugs

Control group

Active

Outcomes

Primary outcome [1]

1. Proportion of patients who show improvement in anxiety scores, by treatment group (improvement’ is defined as 12 week score < baseline score on HADS)

Timepoint [1]

From baseline to 12 weeks.

Primary outcome [2]

2. Proportion of patients who show improvement in QOL (Quality of Life) based on QOLIE-89 scores by treatment group

Timepoint [2]

From baseline to 12 weeks.

Secondary outcome [1]

Neurocognitive

Timepoint [1]

At 12 and 52 weeks.

Secondary outcome [2]

Neuropsychiatric

Timepoint [2]

At 12 and 52 weeks.

Secondary outcome [3]

QOL

Timepoint [3]

At 12 and 52 weeks.

Secondary outcome [4]

Seizure control

Timepoint [4]

At 12 and 52 weeks.

Secondary outcome [5]

Retention rates

Timepoint [5]

At 12 and 52 weeks.

Eligibility

Key inclusion criteria

Patients with Epilepsy (except for primary generalised epilepsy), who have failed treatment with their first anti epileptic drug.

Minimum age

16 Years

Maximum age

90 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Patients with Primary generalised epilepsy, and patients with major psychiatric morbidity, substance abuse, intellectual disability (inability to consent), and those women plannning pregnancy.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Randomization schedule prepared and converted to sealed envelopes by trial statistician who has no contact with patients or recruiting physicians during the trial.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computer generated random binary digits in permuted blocks of variable length.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

27/02/2006

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

200

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

UCB Pharma Belgium

Address [1]

Country [1]

Belgium

Primary sponsor type

Individual

Name

Associate Prof. Terence O'Brien and RMH Neurosciences Foundation

Address

Country

Secondary sponsor category [1]

None

Name [1]

None

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Melbourne Hospital

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

Ethics committee name [2]

Western Hospital

Ethics committee address [2]

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

Ethics approval number [2]

Ethics committee name [3]

St.Vincent

Ethics committee address [3]

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

Approval date [3]

Ethics approval number [3]

Ethics committee name [4]

Alfred

Ethics committee address [4]

Ethics committee country [4]

Australia

Date submitted for ethics approval [4]

Approval date [4]

Ethics approval number [4]

Ethics committee name [5]

Austin hospitals

Ethics committee address [5]

Ethics committee country [5]

Australia

Date submitted for ethics approval [5]

Approval date [5]

Ethics approval number [5]

Summary

Brief summary

Epilepsy is a chronic condition with complex effects on a person’s social, vocational, and psychological function. Physicians are increasingly recognizing that there is more to managing epilepsy than seizure control alone. Side effects of Anti epileptic drugs (drugs used to treat epilepsy), psychiatric and cognitive problems associated with epilepsy are increasingly recognised. Cognition can be loosely explained as an individual’s mental ability to process information and accounts for virtues such as memory, worldly knowledge and problem solving to name a few. It is becoming increasingly recognized that these problems could adversely influence the quality of life of patients, even in those whose seizures are well controlled. The psychiatric and cognitive problems could be due to illness itself or could be due to the side effects of antiepileptic medications. By effectively managing these problems we could maximise the quality of life (QOL) and over all well-being of patients suffering with epilepsy. Only six antiepileptic drugs were available prior to 1990. In the last decade several new anti epileptic drugs have become available increasing our therapeutic options. There has been great deal of research into formulating better anti epileptic drugs, primarily spurred by the fact that the available anti epileptic drugs did not provide adequate control or patients’ were experiencing side effects from drugs. Older Anti epileptic drugs have many undesired side effects. As a group, they have been shown to adversely influence body’s ability to process bodily hormones and drugs. This leads to unwanted side effects such as sexual dysfunction, bone thinning (Osteoporosis), and failure of oral contraceptives to name a few. Side effects such as drowsiness, lethargy and psychiatric and cognitive problems are also more common with older anti epileptic drugs. The newer drugs as a group overall have been shown to have less side effects and are better tolerated. The efficacy of newer drugs is comparable if not superior to older drugs but with less side effects. It is a well-known fact that approximately two thirds of patients would become seizure free with the first or second drug given to them. In recent studies, these treatment responsive patients responded to low doses of essentially all the anti epileptic drugs studied, both old and new. Because these patients will remain on the initial or second therapy for several years, and because they will respond to most drugs, the burden is on the treating physician to select the anti epileptic drug that is most tolerable, has the lowest potential for harm, and has the least likelihood of negatively impacting quality of life.Despite their potential benefits, use of newer anti epileptic drugs thus far is largely limited to refractory cases and to tertiary centres. The newer drugs such as Levetiracetam (Keppra), have the potential to improve quality of life in subjects with epilepsy. The rationale of this project is to compare the tolerability, side effect profile and quality of life outcomes in treatment with levetiracetam versus the “older AEDs” - carbamazepine and valproate; the two drugs most commonly used as first line treatment. We hypothesize that levetiracetam’s efficacy and favourable side effect profile will enhance QOL and will improve health outcomes. We intend to test our hypothesis by prospective assessments of seizure control, cognitive and psychiatric effects and QOL. Cognitive assessments are done through a computerized battery of tests called IntegNeuro. We will also, as part of this study, perform a pilot study of to assess the utility of ocular motility (eye movement) testing as a practical method of assessing anti epileptic drug effects on cognitive performance. It is being increasingly recognized that subtle abnormalities of eye movements are seen in cognitive dysfunction. We intend to perform computerized eye movement testing in a subgroup of 20 patients randomized to each drug, and assess its use as an index of cognitive dysfunction that could be associated with anti epileptic drug use. Psychiatric and QOL assessments are done through well-validated questionnaires. The study population will be patients with epilepsy who have failed treatment with first anti epileptic drug.  Failure is defined as lack of efficacy in controlling seizures or need to stop the drug because of side effects. Previous studies of Levetiracetam have been performed in either medically refractory patients who have taken multiple anti epileptic drugs or newly treated patients, whose clinical course is not yet clear. If positive the results of this study will provide evidence for the earlier use of newer anti epileptic drugs, in particular levetiracetam, especially in early stages of epilepsy and help improve the health outcomes of patients with epilepsy.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Associate Professor Terence O' Brien

Address

Department of Neurology
Royal Melbourne Hospital
4N
Main Building
Grattan St
Parkville VIC 3050

Country

Australia

Phone

+61 3 93427722

Fax

+61 3 93428628

[email protected]

Contact person for scientific queries

Name

Dr Srinivasa Raju Yerra

Address

Royal Melbourne Hospital
4N
Main Building
Grattan St
Parkville VIC 3050

Country

Australia

Phone

+61 3 93427722

Fax

+61 3 93428628

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Monotherapy with Levetiracetam Versus Older AEDs: A Randomized Comparative Trial of Effects on Bone Health.	2016	https://dx.doi.org/10.1007/s00223-016-0109-7

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically