About half of the world's children with epilepsy do not receive treatment - known as the epilepsy treatment gap - with significantly higher rates (67%-90%) in low- and middle-income countries (LMICs). We will conduct the first cluster-randomized clinical trial (cRCT) to determine the efficacy, implementation, and cost-effectiveness of a novel intervention shifting childhood epilepsy care to epilepsy-trained community health extension workers in an effort to close the epilepsy treatment gap. This research will provide information to help extend epilepsy treatment to children in LMICs and worldwide who suffer from untreated seizures.
Epilepsy is the most common severe neurological disorder among children. Most children with epilepsy, if treated, can live normal lives. Yet among the world's children living with epilepsy, about 80% of whom reside in low- and middle-income countries (LMICs), about half do not receive treatment; this is described as "the childhood epilepsy treatment gap." Among the LMICs of Africa, the childhood epilepsy treatment gap is about 67%-90% - unchanged for over twenty years. Although the World Health Organization (WHO) and other health agencies recommend that the epilepsy treatment gap be bridged by task shifting epilepsy care to community health extension workers (CHWs) in primary care settings, this recommendation has not been implemented on a large scale. This failure to scale up task shifting in epilepsy care is due to (a) inadequate evidence of efficacy of task-shifted epilepsy care, (b) a lack of methods and tools for implementing epilepsy task shifting, (c) inadequate understanding of task-shifted epilepsy care barriers, and (d) a lack of cost-effectiveness data for health policymakers. CHWs providing task-shifted epilepsy care must identify children with epilepsy, disadvantaged by stigma and unknown to the healthcare system, who are without access to neurologists or electroencephalograms (EEGs). An epilepsy screening tool in the local language (e.g., Hausa) is therefore essential for epilepsy diagnosis, seizure type classification, and medical management. Hausa, the most commonly spoken language in west Africa, with over 120 million Hausa speakers, is used in daily life, commerce, and education; our proposed study will be conducted in three major cities in Hausa-speaking Africa. Funded by an R21 grant (R21TW010899) in preparation for this cluster-randomized clinical trial (cRCT), we developed and piloted in Kano, Nigeria (a) a scalable epilepsy training program for CHWs, (b) an epilepsy community education program in Hausa to facilitate screening, diagnosis and treatment; and (c) an epilepsy data management system. We also (d) validated an epilepsy screening, diagnosis, and seizure classification tool in Hausa, (e) demonstrated feasibility of screening and enrolling children in a cRCT of task-shifted epilepsy care, and (f) piloted a task-shifted epilepsy diagnosis and management protocol. We will now conduct the first cRCT of task-shifted childhood epilepsy care in Africa with the following specific aims: Conduct a non-inferiority cRCT of a task-shifted childhood epilepsy care protocol compared to enhanced usual care (EUC) in three Hausa-speaking cities in northern Nigeria. We will enroll a maximum of 1800 children (age 6 mo, \<18 yrs) with epilepsy across 60 randomly selected primary healthcare centers (PHCs) in Kano (30 PHCs), Kaduna (16 PHCs) and Zaria (14 PHCs). PHCs will be randomly assigned to intervention (task-shifted to CHWS childhood epilepsy care; 30 PHCs) or EUC (referral to a physician for epilepsy management; 30 PHCs). Primary outcome: we hypothesize that the proportion of children seizure-free for ≥ 6 months at 24 months follow-up (primary outcome) will be similar in the intervention and EUC arms. Secondary outcomes at 24 months include (a) percent seizure reduction from baseline, (b) time to next seizure after 3 months seizure-free, and (c) accuracy of epilepsy diagnosis and seizure type classification by CHWs compared to assessments by physician epilepsy specialists, blinded to the randomization arm. Additional studies of (1) socio-behavioral and implementation outcomes of implementing task-shifted epilepsy care among providers, parents/guardians and patients in the cRCT, and (2) the cost-effectiveness of the task-shifted epilepsy care intervention will performed/completed after completion of the cRCT.
Children with previously untreated epilepsy, identified via community-based screening and diagnositic evaluations, receive epilepsy care (including anti-seizure medication management) from epilepsy-trained community health workers (CHWs).
Children with previously untreated epilepsy, identified via community-based screening and diagnostic evaluations, receive epilepsy care by physicians, as routinely done in Nigeria. The usual physician care is enhanced by community health workers (CHWs), who do not participate in the child's epilepsy care, but who help families navigate the healthcare system.
Federal Neuro-Psychiatric Hospital
Kaduna, Nigeria
Aminu Kano Teaching Hospital
Kano, Nigeria
Ahmadu Bello University Teaching Hospital
Zaria, Nigeria
Percentage Seizure-free for 6 Months, or Longer, Measured at 24 Months After Enrollment
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.
Time frame: Outcome measured 18 months to 24 months after enrollment
75% or Greater Reduction in Seizure Frequency as Determined by the Blinded Physician at 24 Months Follow-up Visit
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.
Time frame: Outcome measured 18 months to 24 months after enrollment
Seizure Freedom for Six Months or Longer in Response to the First Prescribed Anti-epileptic Drug
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.
Time frame: Outcome measured from prescription of the first anti-seizure medication during 24 months after enrollment
Diagnostic Accuracy
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.
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
1,672
Time frame: Diagnostic accuracy measured at 1 month after enrollment.
Mortality
Differences in mortality between study arms that cannot be explained by potential differences in disease severity
Time frame: Deaths measured for 25 months after enrollment.
Number of Children Who Experienced Status Epilepticus
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.
Time frame: Baseline to 24 months after enrollment
Morbidity
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.
Time frame: Morbidity outcomes measured for 24 months after enrollment.
Number of Children for Whom an EEG Was Ordered
Differences by study arm in cumulative number of children for whom EEGs were ordered
Time frame: Baseline to 24 months after enrollment
Task-shifted Protocol Adherence
Reported protocol violations among the study subjects receiving task-shifted epilepsy care from community health workers.
Time frame: Baseline to 24 months after enrollment.
Anytime 6-month Seizure-free Interval
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.
Time frame: Baseline to 24 months after enrollment.