Table 3.
Outcomes and Reasons for Treatment Failure in the Three Study Groups.*
| Result | Ethosuximide | Lamotrigine | Valproic Acid | Overall P Value | Ethosuximide vs. Lamotrigine | Valproic Acid vs. Ethosuximide | Valproic Acid vs. Lamotrigine | |||
|---|---|---|---|---|---|---|---|---|---|---|
| no./total no. (%) | P Value | Odds Ratio (95% CI) | P Value | Odds Ratio (95% CI) | P Value | Odds Ratio (95% CI) | ||||
| Outcome | ||||||||||
| Primary outcome: freedom from treatment failure at wk 16 or wk 20 | 81/154 (53) | 43/146 (29) | 85/146 (58) | <0.001 | <0.001 | 2.66 (1.65–4.28) | 0.35 | 1.26 (0.80–1.98) | <0.001 | 3.34 (2.06–5.42) |
| Secondary outcome: CPT confidence index ≥0.60 | 35/106 (33) | 25/104 (24) | 52/106 (49) | <0.001 | 0.17 | 1.56 (0.85–2.85) | 0.03 | 1.95 (1.12–3.41) | <0.001 | 3.04 (1.69–5.49) |
| Treatment failure | 73/154 (47) | 103/146 (71) | 61/146 (42) | <0.001 | ||||||
| Lack of seizure control | 22/154 (14) | 69/146 (47) | 18/146 (12) | <0.001 | <0.001 | 0.19 (0.11–0.32) | 0.73 | 0.84 (0.43–1.65) | <0.001 | 0.16 (0.09–0.28) |
| EEG seizures only | 10/22 (45) | 20/69 (29) | 4/18 (22) | |||||||
| Seizures either on clinical report or on bedside hyperventilation only | 6/22 (27) | 23/69 (33) | 8/18 (44) | |||||||
| Seizures on EEG and on clinical report, or seizures on EEG and on bedside hyperventilation | 6/22 (27) | 26/69 (38) | 6/18 (33) | |||||||
| Intolerable adverse effects | 37/154 (24) | 25/146 (17) | 35/146 (24) | 0.26 | 0.15 | 1.53 (0.87–2.70) | 0.99 | 1.00 (0.59–1.69) | 0.19 | 1.53 (0.86–2.71) |
| Nervous system, behavioral, or psychological effects | 12/37 (32) | 9/25 (36) | 20/35 (57) | |||||||
| Digestive disorders | 9/37 (24) | 3/25 (12) | 6/35 (17) | |||||||
| Rash† | 6/37 (16) | 5/25 (20) | 2/35 (6) | |||||||
| Fatigue | 3/37 (8) | 2/25 (8) | 5/35 (14) | |||||||
| Headache | 3/37 (8) | 2/25 (8) | 2/35 (6) | |||||||
| BMI increase that met exit criterion | 0 | 1/25 (4) | 4/35 (11) | |||||||
| Laboratory abnormality | 1/37 (3) | 2/25 (8) | 2/35 (6) | |||||||
| Other | 4/37 (11) | 4/25 (16) | 5/35 (14) | |||||||
| Withdrawal from study | 20/154 (13) | 18/146 (12) | 15/146 (10) | 0.78 | 0.99 | 1.06 (0.54–2.10) | 0.48 | 0.77 (0.38–1.56) | 0.71 | 0.81 (0.39–1.68) |
| Local investigator’s decision | 4/20 (20) | 2/18 (11) | 6/15 (40) | |||||||
| Parent or guardian’s decision | 15/20 (75) | 16/18 (89) | 11/15 (73) | |||||||
| Blinding broken | 1/20 (5) | 1/18 (6) | 1/15 (7) | |||||||
| Study drug discontinued; no reason reported | 0 | 1/146 (<1) | 0 | |||||||
*
BMI denotes body-mass index, CPT Conners’ Continuous Performance Test, and EEG electroencephalogram.
†
Rash was considered by investigators to be at least moderately severe and possibly drug-related.