The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy—an open-label, prospective, randomised controlled multicenter study
- Felix Rosenow1,
- Carmen Schade-Brittinger2,
- Nicole Burchardi2,
- Sebastian Bauer1,
- Karl Martin Klein1,
- Yvonne Weber3,4,
- Holger Lerche3,4,
- Stefan Evers5,
- Stjepana Kovac5,
- Susanne Hallmeyer-Elgner6,
- Götz Winkler7,
- Joachim Springub8,
- Mathias Niedhammer9,
- Erhard Roth10,
- Ilonka Eisensehr11,
- Jörg Berrouschot12,
- Stephan Arnold13,
- Michael Schröder14,
- Anja Beige14,
- Wolfgang H Oertel1,
- Adam Strzelczyk1,
- Anja Haag1,
- Philipp S Reif1,
- Hajo M Hamer1,
- for the LaLiMo Study Group*
- 1Department of Neurology, Epilepsy Center Hessen, University Hospitals Giessen & Marburg and Philipps-University Marburg, Germany
- 2Coordinating Center for Clinical Trials (KKS), Philipps-University Marburg, Marburg, Germany
- 3Department of Neurology, University of Ulm, Ulm, Germany
- 4Department of Neurology and Epileptology, University Hospital Tuebingen, Tuebingen, Germany
- 5Department of Neurology, University of Münster, Münster, Germany
- 6Department of Neurology, University of Dresden, Dresden, Germany
- 7Department of Neurology, Leopoldina Hospital, Schweinfurt, Germany
- 8Private Neurological Practice, Westerstede, Germany
- 9Private Neurological Practice, Oldenburg, Germany
- 10Private Neurological Practice, Lich, Germany
- 11Private Neurological Practice, Munich, Germany
- 12Department of Neurology, District Hospital Altenburg, Altenburg, Germany
- 13Department of Neurology, University of Regensburg, Regensburg, Germany
- 14Private Neurological Practice, Munich, Germany
- Correspondence to Professor Felix Rosenow, Epilepsy Center Hessen, Department of Neurology, University Hospitals Giessen & Marburg, Baldingerstrasse, 35043 Marburg, Germany;
Contributors FR, HMH and CS-B designed the study and wrote the study protocol. CS-B, FR and NB drafted and amended the statistical analysis plan and NB was responsible for the biometrical analyses in the study. FR, CS-B, HMH and AH reviewed the statistical analysis. FR, SB, KMK, YW, HL, SA, AB, SE, SK, S-HE, GW, JS, MN, ER, IE, JB, MS, AS and PSR had initially approved the protocol and were actively involved in patient recruitment and data collection. SB and PSR were actively involved in data quality assurance and monitoring. FR, NB, CS-B, HMH, WHO, PSR and AS actively contributed to the writing and reviewing of the submitted manuscript. All authors reviewed the manuscript and approved the final version.
- Received 8 December 2011
- Revised 22 February 2012
- Accepted 27 February 2012
- Published Online First 17 May 2012
Background Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy.
Methods A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed.
Results The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07).
Conclusions There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm.
Clinical trial registration number ClinicalTrials.gov identifier NCT00242606.
- First seizure
- epilepsy treatment
- cerebrovascular disease
- health economics
PSR and HMH contributed equally to this work.
Funding UCB Pharma was involved in the study design and provided personnel for regular monitoring visits. UCB Pharma was not involved in data analysis, interpretation of the data and in the decision to submit the paper for publication.
Competing interests This study was sponsored by Philipps-University Marburg, Marburg, Germany. UCB Pharma provided the majority of the funding. Several of the authors have received honoraria and research and travel grants from UCB Pharma, the producer of LEV, and GSK the original producer of LTG.
Ethics approval This study was approved by the ethics committee of the University of Marburg, Germany.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement For data sharing requests please contact FR ( ).