Clinical trial NCT04290975: Bridging the Childhood Epilepsy Treatment Gap in Africa
Official title: Bridging the Childhood Epilepsy Treatment Gap in Africa (BRIDGE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Epilepsy
Keywords: Epilepsy
Pediatric
Neurology
Nigeria
Task-shifting
Africa
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Aminu Kano Teaching Hospital
name: Ahmadu Bello University Teaching Hospital
name: Federal Neuro-Psychiatric Hospital, Kaduna
First posted: 2020-03-02
Enrollment: 1800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The basic framework of these studies is a cRCTin which 60 PHCs (clusters) will be randomly selected from about 399 eligible PHCs in three major cities in the Hausa-speaking areas of northern Nigeria -30 of about 167 PHCs in Kano, 15 of about 124 PHCs in Kaduna, and 15 of about 108 PHCs in Zaria. Half of the overall PHCs will be randomly assigned to the task-shifted care arm of the cRCT, in which epilepsy treatment and follow-up care is provided by a CHW. The other half will be assigned to "enhanced usual care" in which the care is provided by a physician and a CHW serves to record events and collect other standardized data.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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:

1. 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.
2. Assess socio-behavioral and implementation outcomes among providers, parents/guardians and patients in the cRCT. Outcome measures include: (1) Difference in baseline, 12- and 24-month intervention acceptability, appropriateness, and feasibility measures among providers in the task-shifted intervention arm of the cRCT; (2) Difference in baseline, 12- and 24-month quality of life, epilepsy knowledge and stigma, and trust in the healthcare system and providers among participants; (3) Comparison of 12- and 24-month quality of life, knowledge and stigma and trust measures among participants in the intervention and control arms.
3. Determine the cost-effectiveness of the task-shifted epilepsy care intervention. Direct costs of the intervention and EUC will include personnel costs (including CHW epilepsy training) and expenses for diagnostic (EEG, brain imaging) and laboratory tests and anti-epileptic drugs. Indirect costs will include travel time and time away from work for parents/guardians and change in school attendance for patients. Cost-effectiveness will be expressed as US dollars per disability adjusted life year (DALY) averted.

This project will also establish a brain disorders clinical research network for Hausa-speaking Africa and provide data for health system leaders and policymakers to scale-up task-shifted childhood epilepsy care.

Eligibility criteria: Inclusion Criteria:

* Resident of Kano or Kaduna states and living in the Kano, Zaria, or Kaduna metropolitan areas of northern Nigeria
* Parent or guardian provided informed consent for the screening questionnaire given to the parent/guardian
* Parent or guardian informed consent, plus assent for children \>7 years able to provide assent, for epilepsy diagnostic evaluation if the screening for possible epilepsy is positive
* Diagnosed with possible epilepsy through initial screening, and then diagnosed with epilepsy upon further evaluation by an epilepsy-trained CHW working with the BRIDGE project, who may consult a BRIDGE physician for diagnostic questions
* Parent or guardian provided consent, and assent for children \>7 years able to provide assent, for enrollment in the cRCT of task-shifted epilepsy care versus enhanced physician epilepsy care

Exclusion Criteria:

* Children who have previously been diagnosed with epilepsy and are currently enrolled in other care and treatment, or who have been treated for epilepsy within three months prior to screening
* Children who are currently receiving care by a neurologist or neurosurgeon for a serious brain disorder (e.g., brain tumor, stroke)
* Lack of informed consent, and/or lack of assent from children \>7 years who are able to provide assent.Inability of the parent or guardian to communicate with healthcare providers in either Hausa or English
* Any child who screens positive for epilepsy, has epilepsy upon clinical evaluation, but does not live in Kano, Zaria, and Kaduna, and who is in the judgement of the parents and/or BRIDGE staff to be unable to comply with the study visits because of travel distance from home.

Primary outcomes:
measure: Percentage seizure-free
timeFrame: Must be seizure-free for 6 or more months at the 24-month visit follow-up visit
Secondary outcomes:
measure: Reduction in seizure frequency
timeFrame: Evaluated at 24 months in both arms compared to enrollment (baseline) data
measure: Seizure freedom in response to first prescribed anti-epileptic drug
timeFrame: 6 months after enrollment of final subject
measure: Diagnostic accuracy
timeFrame: Evaluated by blinded physicians at 1, 6, 12, 18, and 24 months after enrollment
measure: Mortality
timeFrame: Once, at study conclusion (24 months after enrollment of final subject)
measure: Status epilepticus
timeFrame: Assessed at 1 month, 6 months, 12 months, 18 months and 24 months after enrollment, with analysis of outcome at study conclusion (24 months after enrollment of final subject)
measure: Morbidity
timeFrame: Once, at study conclusion (24 months after enrollment of final subject)
measure: Diagnostic tests ordered
timeFrame: Once, at study conclusion (24 months after enrollment of final subject)
measure: Task-shifted protocol adherence
timeFrame: Once, at study conclusion (24 months after enrollment of final subject)
measure: Anytime 6-month seizure-free interval
timeFrame: Assessed at 4 time points during 24-month follow-up: 6, 12, 18, and 24 months
Other outcomes:
measure: Cost-effectiveness of task-shifted care
timeFrame: Data collection over 24 months after enrollment, with analysis of cost-effectiveness data after the final study subject completes the 24-month follow-up visit.
Locations:
city: Kaduna
country: Nigeria
facility: Federal Neuro-Psychiatric Hospital
city: Kano
country: Nigeria
facility: Aminu Kano Teaching Hospital
city: Zaria
country: Nigeria
facility: Ahmadu Bello University Teaching Hospital
Study officials:
affiliation: Vanderbilt University Medical Center
name: Edwin Trevathan, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Aminu Kano Teaching Hospital
name: Aminu Taura, MBBS
role: PRINCIPAL_INVESTIGATOR
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