Interventieonderzoek (trials en cohort)
Study reference Study characteristics Patient characteristics Intervention (I) Comparison / control (C) Follow-up Outcome measures and effect size Comments

Noachtar, 2008

Type of study:

Randomized, doubleblind, placebo-controlled, parallel-group study

 

Setting:

Multicenter (37 centres in 14 countries)

 

Country:

Germany

 

Source of funding:

NR

Inclusion criteria:

Age 12-65 with diagnosis IGE with myoclonic seizures, according to ILAE classification on ≥8 days during study baseline period of 8 wks.

 

Exclusion criteria:

Females of childbearing potential without medically accepted contraceptive method, nonepileptic seizures

within the previous year, signs suggestive of a progressive

brain lesion, history of partial-onset seizures, status epilepticus

within the previous 3 months, previous or current treatment

with levetiracetam, current use of vigabatrin, tiagabine or felbamate with less than 18

months exposure.

 

N: 121 (intent to treat)

 

Intervention group:

N: 61

 

Mean age ± SD:

25.0 ± 7.4

 

Sex: 36.1% M (22) / 63.9% F (39)

 

Control group:

N: 60

 

Mean age ± SD:

26.8 ± 9.5

Sex: 36.7% M (22) / 63.3% F (38)

 

Groups comparable at baseline?

Yes

Adjuvant levetiracetam (tablets of 500 mg)

 

Treatment was initiated with 2 tablets/ day (1000 mg/day), increasing at 2-week intervals to 4 tablets/day (2000 mg/day) and then 6 tablets/day (3000 mg/day).

 

After these 4 wks an evaluation period of 12 wks followed with a single fall-back option to 2000 mg/day during the first week.

Adjuvant placebo

 

Treatment was initiated with 2 tablets/ day ,increasing at 2-week intervals to 4 tablets/day and then 6 tablets/day.

 

After these 4 wks an evaluation period of 12 wks followed with a single fall-back option to 4 tablets/day.

Endpoint of follow-up:

16 wks (of which 4 up-titration and 12 evaluation, without baseline of 8 wks and down-titration of 6 wks)

 

For how many participants were no complete outcome data available?

 

Intervention group:

N (%): 1/61 (1.6%)

 

Control group:

N (%): 0/60 (0.0%)

 

Reasons for incomplete outcome data described?

Lost to follow-up in first 2 weeks of up-titration period

 

Significant differences between groups?

No

Seizure-free during 16-wk treatment period

I: 8/60 (13.3%)

C: 0/60 (0.0%)

P= 0.006

 

Seizure-free during 12-wk evaluation period

I: 13/60 (21.7%)

C: 1/60 (1.7%)

P<0.001.

 

Adverse events (during treatment period)

I (45/60): headache (n=13), somnolence (n=6), neck pain (n=5), pharyngitis (n=4), fatique (n=3), vertigo (n=3), depression (n=3), nasopharyngitis (n=2), nervousness (n=2), dizziness (n=2)

C (40/60): headache (n=14), somnolence (n=1), neck pain (n=1), fatique (n=6), vertigo (n=2), depression (n=1), nasopharyngitis (n=4), nervousness (n=4), dizziness (n=3)

- The majority of the subjects were diagnosed as juvenile myoclonic epilepsy (88.5% in the intervention group, 98.3% in the contro group), others were diagnosed juvenile absence epilepsy)

- 122 patients were randomized, but 1 did not receive medication, so 121 were included in the intent to treat

- About patients with IGE, not only about JME: a small part (8/121) has juvenile absence epilepsy

Specchio, 2006

Type of study:

Prospective, pragmatic, longterm, open-label treatment study

 

Setting:

Multicenter

 

Country:

Italy

 

Source of funding: NR

Inclusion criteria:

Patients with definitive diagnosis of JME as defined by ILAEC and incomplete control of myoclonic and GTC seizures despite optimal treatment and/or poor tolerability to previous AEDs.

 

Exclusion criteria:

Insufficient documentation of seizure frequency, poor compliance, progressive neurological diseases, severe psychiatric disorders, drug or alcohol abuse, internal diseases, laboratory abnormalities, pregnancy or lactation.

 

N: 48

 

Mean age ± SD:

27.4 ± 8.5 (range 15-50)

 

Sex: 20.8% M (10)/ 79.2% F (38)

Adjuvant levetiracetam

 

After 8-wk baseline period, patients were given levetiracetam at a starting dose of 250 mg twice a day. This was increased to 500 mg twice a day after a dixed 2-wk titration period. Than an observation period of 36 months followed. During this period, the dose could be increased up to 1200 mg twice a day according to clinician judgement.

No control

Endpoint of follow-up:

Mean 19 months (range 0.3-38)

 

For how many participants were no complete outcome data available?

 

N (%): 5/48 (10.4%)

 

Reasons for incomplete outcome data described?

Lack of efficacy (n=3), occurrence of a first GTC seizure (n=1) and pregnancy (n=1)

Seizure-free:

16/48 (33.3%)

 

Side-effects (5/48):

somnolence(n=3), nervousness (n=2)

-small study population

Biton et al., 2005

Type of study:

Post-hoc analysis of a patient subset from 2 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. 

Setting:

Eighteen centers in the United States; 10 centers in Europe; 1 center in Costa Rica (primary trials)

Source of funding:

This study was sponsored by Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ.

Inclusion criteria:

Patients with at least 3 PGTCS during an 8-week baseline period were eligible. Patients had to have an electroencephalogram or closed circuit  television/ electroencephalogram consistent with generalized epilepsy. 

Exclusion criteria:

Not specified

 

N: 22

 

Mean age ± SD:

I: 34

C: 27

 

Sex: 

I: 64%F

C:64%F

Other important characteristics:

-

 

Groups comparable at baseline?

Yes (identical because cross-over study)

Topiramate 50 mg/dag maintained for four weeks, then increased at two-week intervals to target dosages of 400 mg/dag for adults or 6 mg/dag in children. Treatment was continued another 12 weeks.

Equivalent placebo tablets

Endpoint of follow-up:

12 weeks

 

For how many participants were no complete outcome data available?

 

N (%): 3/19 (15.8%)

 

Reasons for incomplete outcome data described?

?

 Significant differences between groups?

Unclear: ?

Seizure-free:

Not reported

 

50% reduction in seizures:

I: 73%

C: 18%

 

Adverse events:

nausea (n = 5), insomnia (n = 3), upper respiratory tract infection (n = 3), abnormal vision (n = 2), appetite decrease (n = 2), concentration/attention difficulty (n = 2), diarrhea (n = 2), epistaxis (n = 2), and flu-like symptoms (n = 2). Three placebo-treated patients experienced nausea, 2 reported upper respiratory tract infection, and abnormal vision and diarrhea were each reported by 1 patient. Two topiramate patients and 1 placebo patient discontinued treatment owing to adverse events.

- small study population

- majority of patients (64%)were treated with two AEDs before topiramate was added