Epilepsy
Conditions
Keywords
Epilepsy, Pediatric, Neurology, Nigeria, Task-shifting, Africa
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: 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.
Interventions
OTHERTask-shifting epilepsy care to epilepsy-trained community health workers (CHWs)
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).
OTHEREnhanced usual care for epilepsy (EUC)
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.
Sponsors
Vanderbilt University Medical Center
Aminu Kano Teaching Hospital
Ahmadu Bello University Teaching Hospital
Federal Neuro-Psychiatric Hospital, Kaduna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
Four epilepsy-trained physicians served as blinded physicians for the study, and evaluated every study subjects in both arms at 1, 6, 12, 18, and 24 months after enrollment. These blinded physicians had no other role in the cRCT other than to serve as the gold standard for the diagnosis of epilepsy, to determine study subjects' seizure frequency, potential anti-seizure medication (ASM)-related adverse events and monitored each child's exam and development. Blinded physicians entered clinical data into case report forms on their study-dedicated android tablet computers, with data uploaded to the study data office and the data coordinating center. Parents/guardians, study staff and co-investigators were instructed to not disclose the study arm of study subjects with blinded physicians. Blinded physicians were not included in study meetings, did not have access to study offices or study data, and met separately with study principal investigators to address any study related issues.
Intervention model description
This is a cluster randomized clinical trial (cRCT) in which 60 primarily healthcare centers (PHCs), each serving a defined community, are designated as the 60 clusters. The clusters were randomly selected from 398 eligible PHCs in three major cities in the Hausa-speaking areas of northern Nigeria -30 of about 167 PHCs in Kano, 15 of 123 PHCs in Kaduna, and 15 of about 108 PHCs in Zaria. Half of the overall PHCs were randomly assigned to the task-shifted childhood epilepsy care (TSC) arm of the cRCT, in which childhood epilepsy treatment and follow-up care is provided by a CHW. The other half were assigned to "enhanced usual care" (EUC) in which the care is provided by a physician and a CHW serves to record events and collect other standardized data. Children with previously untreated epilepsy were enrolled and assigned to PHCs based upon the participating PHC closest to their home. CHWs and mothers were not considered enrolled in the study.
Eligibility
Sex/Gender
ALL
Age
6 Months to 16 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Seizure-free for 6 Months, or Longer, Measured at 24 Months After Enrollment | Outcome measured 18 months to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 75% or Greater Reduction in Seizure Frequency as Determined by the Blinded Physician at 24 Months Follow-up Visit | Outcome measured 18 months to 24 months after enrollment | 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. |
| Seizure Freedom for Six Months or Longer in Response to the First Prescribed Anti-epileptic Drug | Outcome measured from prescription of the first anti-seizure medication during 24 months after enrollment | 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 | Diagnostic accuracy measured at 1 month after enrollment. | 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. |
| Number of Children Who Experienced Status Epilepticus | Baseline to 24 months after enrollment | 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. |
| Morbidity | Morbidity outcomes measured for 24 months after enrollment. | 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. |
| Number of Children for Whom an EEG Was Ordered | Baseline to 24 months after enrollment | Differences by study arm in cumulative number of children for whom EEGs were ordered |
| Task-shifted Protocol Adherence | Baseline to 24 months after enrollment. | Reported protocol violations among the study subjects receiving task-shifted epilepsy care from community health workers. |
| Mortality | Deaths measured for 25 months after enrollment. | Differences in mortality between study arms that cannot be explained by potential differences in disease severity |
| Anytime 6-month Seizure-free Interval | Baseline to 24 months after enrollment. | 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. |
Countries
Nigeria
Contacts
PRINCIPAL_INVESTIGATOREdwin Trevathan, MD, MPH
Vanderbilt University Medical Center
PRINCIPAL_INVESTIGATORAminu Taura, MBBS
Aminu Kano Teaching Hospital
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 1672 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Mean Baseline Seizures per month | 18.8 Number of Seizures per Month STANDARD_DEVIATION 18.7 |
| Race/Ethnicity, Customized Ethnicity Fulani | 71 Participants |
| Race/Ethnicity, Customized Ethnicity Hausa | 1529 Participants |
| Race/Ethnicity, Customized Ethnicity Igbo | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 26 Participants |
| Race/Ethnicity, Customized Ethnicity Yoruba | 12 Participants |
| Region of Enrollment Nigeria | 1672 participants |
| Sex: Female, Male Female | 289 Participants |
| Sex: Female, Male Male | 537 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 50 / 846 | 54 / 826 |
| other Total, other adverse events | 7 / 846 | 7 / 826 |
| serious Total, serious adverse events | 33 / 846 | 25 / 826 |
Outcome results
None listed