Shorvon 2000.
| Methods | Randomised double‐blind placebo‐controlled crossover trial 3 treatment arms: 1 PCB and 2 LEV Randomisation concealment: allocated sequentially sealed, numbered packages containing either LEV or PCB. Random list generation: random permuted blocks (size 6) Blinding: identical tablets and packages. Investigators and staff were described as blinded to treatment assignment. If treatment code was broken, the patient had to be removed from the trial Baseline = 8 to 12 weeks. Treatment period = 16 weeks (4 weeks' titration, 12 weeks' maintenance) |
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| Participants | All adults. Multicentre across Europe
Total randomised 324 adults; all with drug‐resistant focal epilepsy but a few also had generalised‐onset or unclassified seizures, or both
112 adults to PCB 106 adults to LEV 1000 mg 106 adults to LEV 2000 mg 49% male Age range 14 to 69 years Other AEDs: 1 or 2 ≥ 4 focal seizures per 4 weeks during 8‐ or 12‐week baseline ≥ 2‐year history of uncontrolled focal epilepsy Mean duration of epilepsy (± SD) (years): LEV 1000 mg = 23.8 ± 12.3; LEV 2000 mg = 23.6 ± 13.3; PCB = 23.2 ± 11.0; overall = 23.6 ± 12.2 Mean baseline seizure frequency per week: 2.62; range 0.3 to 102.7 |
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| Interventions | LEV 1000 mg LEV 2000 mg PCB Up‐titration dosages = LEV was titrated upwards in twice‐daily increments of 500 mg at 2‐week intervals until patients were stabilised on their assigned dosages (1000 mg/day or 2000 mg/day). The 1000‐mg LEV group received PCB for 2 weeks before initiation of active drug |
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| Outcomes | ≥ 50% reduction in seizure frequency Treatment withdrawal Adverse effects QoL and cognitive effects |
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| Notes | 2 participants excluded from 50% responder analysis: 1 in LEV 2000 mg, 1 in PCB A few participants had generalised‐onset or unclassified seizures, or both, in addition to partial‐onset seizures QoL was assessed using the ESI‐55 for 92 participants in LEV 1000 mg and LEV 2000 mg, and 89 participants in PCB |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | A ‐ Adequate |
| Allocation concealment (selection bias) | Low risk | A ‐ Adequate |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | A ‐ Adequate |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | A ‐ Adequate |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | A ‐ Adequate |
| Selective reporting (reporting bias) | Low risk | A ‐ Adequate |