Trial Outcomes & Findings for Bridging the Childhood Epilepsy Treatment Gap in Africa (NCT NCT04290975)

June 15, 2020 - Sept. 9, 2021, mothers of 41,623 children in the study area consented to their children being screened for epilepsy. Of 1852 children who screened positive for epilepsy, 1764 children (TSC=879 in 30 clusters; EUC=885 in 30 clusters) were initially diagnosed with epilepsy; 1672 children with a final diagnosis of epilepsy (TSC=846 in 30 clusters; EUC=826 in 30 clusters) enrolled in the epilepsy outcomes cluster RCT. Neither mothers nor CHWs were considered enrolled in the RCT.

Children who screened positive for epilepsy were assigned to a study arm (TSC or EUC) based upon their home address, and whether the participating PHC (cluster) closest to their home was randomly assigned to TSC or EUC. Among children with positive epilepsy screens, those who lived in a TSC area were referred to the PHC for diagnosis and treatment by an epilepsy-trained CHW, who followed the task-shifted protocol; those in EUC areas were referred to physicians for diagnosis and treatment.

Unit of analysis: Clusters (Primary Healthcare Centers)

Bridging the Childhood Epilepsy Treatment Gap in Africa

Percentage of children in each arm of the study who were seizure-free for 6 months, or longer, measured specifically at 24 months after enrollment. Physicians with expertise in epilepsy, blinded as to study arm, utilized review of seizure diaries maintained by parents plus medical history, to determine whether each child had been seizure free for six months, or longer, 24 months after enrollment in the cluster RCT.

75% or greater reduction in seizure frequency (including seizure freedom) for 6 months or longer was determined by the blinded physician at the 24-month follow-up visit, compared to seizure frequency reported at time of enrollment. Outcome variance estimates were adjusted for cluster correlation. At 24 months this secondary outcome is captured for 1488 of 1672 randomized, eligible patients. 101/826 (12.2%) EUC patients and 83/846 (9.8%) TSC patients are missing the secondary outcome at 24 months.

Percentage of children seizure-free for 6 months or longer in response to the first anti-epileptic drug prescribed, as measured by questions in standardized case report forms completed by physicians with epilepsy expertise, blinded as to the arm of the study. The blinded physicians will review a daily seizure log which indicates the occurrence and duration of each seizure, maintained by the parent/guardian, to facilitate the blinded physician evaluation.

Diagnostic accuracy was determined based upon diagnosis of epilepsy (or"not epilepsy") by physicians with expertise in epilepsy, blinded as to study arm, or "blinded physicians". Non-inferiority of TSC arm diagnostic accuracy was declared if the lower limit for the ratio of the odds of being accurately diagnosed in the intervention (TSC) versus standard-of-care enhanced by community health workers (CHWs) helping parents navigate the healthcare system is below the odds ratio implied by a 10% absolute difference between study arms.

Differences in mortality between study arms that cannot be explained by potential differences in disease severity

Difference in the number of children who experienced status epilepticus among children in both arms of the study, as measured by questions in standardized case report forms completed by physicians with expertise in epilepsy, who are blinded as to the arm of the study. The blinded physicians will review a daily seizure log which indicates estimated seizure duration for each seizure, maintained by the parent/guardian, to facilitate the blinded physician evaluation.

Differences in morbidity, including neurodevelopmental morbidity (e.g., cerebral palsy), associated with epilepsy between study arms that emerged during the cRCT. Evaluations for CP were conducted during the 24-month follow-up period. Evaluations for wasting and for stunting were performed during follow-up visits of the 24-month study.

Differences by study arm in cumulative number of children for whom EEGs were ordered

Reported protocol violations among the study subjects receiving task-shifted epilepsy care from community health workers.

6-month seizure-free intervals as determined by evaluations by physicians with expertise in epilepsy, blinded as to the arm of the study, at 6 months, 12 months, 18 months and 24 months after enrollment. These blinded physicians with expertise in epilepsy will record seizure frequency (including seizure-freedom) on standardized case report forms, facilitated by blinded physician review of daily seizure logs maintained by parents/guardians that will indicate the specific dates and durations of all recorded seizures.

Seizure disability weights were determined for all enrolled children in each arm of the cluster randomized clinical trial (cRCT), beginning with information from enrollment, collected at each study visit, for the total duration of the study subject's enrollment in the study. For each follow-up visit, we computed average monthly seizure frequency over the reported study intervals. We time-weighted the disability weights across the 24-month study horizon for each enrolled child. The seizure disability weights are measured on a 0-1 scale, with "0" representing perfect health and "1" representing death. The seizure disability weight represents the severity of a non-fatal health state, with the lower score being more favorable.