Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT02744521 |
Other study ID # |
MaastrichtU |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
N/A
|
First received |
March 20, 2016 |
Last updated |
April 16, 2016 |
Start date |
March 2016 |
Study information
Verified date |
April 2016 |
Source |
Maastricht University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
Ethiopia: Ethical Review Committee |
Study type |
Interventional
|
Clinical Trial Summary
Introduction: Finding and successfully treating all tuberculosis (TB) patients is the
cornerstone of the Global Strategy to Stop TB. However, many patients in resource-limited
countries remain undiagnosed. Prisons are a well-known source of undetected TB. Thus, there
is a need to find feasible interventions to find and treat TB patients in these settings.
Objective: The objective of this study is to evaluate whether empowering and involving
inmate peer educators in TB control has an impact on increasing TB case detection rate and
improving treatment success in resource-limited prison settings.
Methodology: This is a matched cluster randomized control trial where randomization to the
intervention and treatment groups will be carried out within pairs. Eight matched prison
pairs will be randomly selected for this study in which eight prisons from each pair will be
randomly assigned to the intervention and the remaining to the control group. Trained prison
peer educators at the intervention sites will organize and provide education about TB every
two weeks on a regular basis for one year. Peer educators will also perform routine TB
screening, using a screening protocol to identify presumptive TB cases for a referral.
Identified presumptive TB cases will then be linked to the prison health personnel for a
referral to nearby hospitals. The TB diagnosis will be carried out at the referral sites
using the routine direct smear microscopy and/or chest X-ray (Radiography). Tuberculosis
case finding in the control sites will follow the existing referral system (self-referral to
nearby hospitals) and the diagnosis will be undertaken using direct sputum microscopy and/or
chest X-ray as in the intervention sites. The data will be entered using Epi Data entry
version 3.1 software and analyzed using SPSS version 20.0. Considering prisons as a unit of
analysis, the mean Case Detection Rate (CDR), Treatment Success Rate (TSR) and the
percentage of patients symptomatic for > =3 months will be compared within pairs using the
paired t-test or sign test as appropriate.
Description:
1. Background and justification
Although the global incidence of tuberculosis (TB) has fallen by an average rate of
1.5% per year between the years 2000 and 2013, TB remains a major global health problem
and is the second leading cause of death from infectious diseases [1,2]. An estimated 9
million people had developed TB in the year 2013 of which one-quarter was from Africa,
the continent that also has the highest rates of cases and deaths relative to its
population [1,3]. In the same year, only 5.7 million cases were both detected and
notified to the National TB programs (NTPs), meaning that about 3 million people were
"missed" by TB control programs [1]. The TB case detection rate (calculated as
notifications of new and relapse cases divided by the estimated incidence per year) was
only 64% at the global level and is below the World Health Organization (WHO) target
(70%) [1].
Tuberculosis disproportionately affects vulnerable populations such as prisoners.
According to a review of studies from both high and low-income countries, the
prevalence of TB in prisons was 3 to 200-fold higher than in the general population
[4,5]. A number of factors such as overcrowding, inadequate ventilation, delayed case
detection and the movement of prisoners from site to the site make prisons a high-risk
environment for TB transmission [6]. The emergence of drug-resistant TB has also made
TB control efforts very complicated in prisons. [7]. If untreated, prisoners with
drug-resistant TB will be an additional health hazard for fellow prisoners and staff
[8]. Furthermore, TB and resistant forms of TB can spill out into the community and
create a public health hazard [9]. In sub-Saharan African prisons, the high burden of
human immunodeficiency virus (HIV) infection and poverty make the problem much worse
[10]. Health care services are also very limited and due to the lack of diagnostic
facilities many TB patients remain undetected [11]. In a recent study from a South
African prison, for example, the prevalence of undiagnosed TB was reported to be high
at 3.5% [12].
Ethiopia, which ranks 8th of the 22 countries with a high burden of TB [13], has
implemented the directly observed treatment short-course (DOTS) program since 1992
[14]. Currently, the country has achieved the Millennium Development Goals (MDGs) of
halving TB incidence, prevalence, and mortality by 2015 [1]. However, the case
detection rate (CDR) remains low as in many other developing countries.
The case detection rate of all forms of TB was reported to be 62% which is still below
the WHO target [1]. Ethiopia is listed among the top ten countries that accounted for
74% (2.4% million) of missed TB cases [1]. Shortage of health workers, low service
coverage, low health seeking behavior and lack of efficient TB diagnostics are some of
the factors for the low case detection rate in the country [15].
Tuberculosis detection is a huge challenge for Ethiopian prisons [7,16]. Because of
lack of skilled health professionals and laboratory facilities, TB diagnosis relies on
a referral of prisoners to health facilities outside prisons. As prisoners often do not
recognize the symptoms of TB or use non-TB medicines to relieve symptoms, TB diagnosis
is often severely late [17,18]. As a consequence, many prisoners with TB in the
Ethiopian prisons remain undiagnosed [19]. Recently, we reported that at least half of
symptomatic pulmonary TB cases were left undiagnosed and hence untreated in Northern
Ethiopian prisons [20]. Some of these patients remained undiagnosed for more than two
years [20]. This creates an opportunity for the transmission and dissemination of TB
not only among prisoners but also to the general community. In addition, although
accurate data is not available on TB treatment adherence, the conditions in Ethiopian
prisons make the TB treatment supervision difficult and hence adherence to the full
course of anti-TB drugs remains a challenge to TB patients [20]. This will lead to the
emergence of drug-resistant strains, an important challenge for TB control. Thus,
efforts are needed to improve TB case detection and treatment adherence in Ethiopian
prisons. Epidemiological models show that employing active case finding through entry
and exit screening, and frequent mass screening, using a combination of diagnostic
tools (usually sputum smear microscopy and chest-X-ray), improves TB case detection in
prisons [21]. However, resource constraints and lack of skilled health professionals
limit its applicability in prisons of poor countries. Increasing the health service
coverage and training health workers to fill the gap in short period seems a remote
possibility. Therefore, there is a need to find alternative ways that could increase
access to diagnostic and treatment services, ultimately increasing TB case detection
and treatment success rate. In the current study, the investigators plan to undertake a
cluster randomized controlled trial to assess whether empowering and involving inmate
peer educators in the TB control improves TB case detection, treatment success rate,
and pre-treatment symptom duration in a resource-limited prison setting.
2. Hypotheses
Hypothesis 1: Case detection rate: Compared to the control sites, the TB case detection
rate in the intervention sites will be increased by 50%.
Hypothesis 2: Treatment success rate: Compared to the control sites, treatment success
rate in the intervention sites will be increased by 10%.
Hypothesis 3: Pre-treatment symptom duration: Compared to the control sites, the
proportion of patients with pre-treatment symptom duration of >=3 months will be
reduced by 30% in the intervention sites.
3. Methods 3.1. Study area and study population
This study will be conducted in Northern Ethiopian prisons. Ethiopia had an officially
registered prison population of 112,361 (136/100,000 persons) in 2010 [22], which is
higher than the imprisonment rates observed in some sub-Saharan African countries such
as in Kenya (121/100,000 persons), and Malawi (76/100,000 persons). The fact that
prisons are overcrowded and inadequately ventilated means that Ethiopian prisons are
ideal for the transmission of Mycobacterium tuberculosis [23] and urge appropriate
interventions. This interventional study will be conducted in 16 main prisons (8
matched pairs) located in the Amhara and Tigray regions including Mekelle vs. Shire,
Adawa vs. Tembien, Humera vs. Adigrat, Mychew vs. Alamata, Wukro vs Axum, Dessie vs.
Woldya, Fenoteselam vs. Debremarkos, and Debretabor vs. Bahir Dar for a one year period
from March 2016 to March 2017. This interventional study focuses only in prisons of the
Northern Ethiopia considering feasibility. All the prisoners in the 16 selected prisons
are study populations.
3.2. Study design and inclusion criteria
This is a matched cluster randomized controlled trial where randomization to the
intervention and treatment groups will be carried out within pairs. Prisons will be
matched into pairs on the basis of their location and/or the number of prisoners.
Larger prison sites located in the main cities of Amhara and Tigray regions will be
considered as eligible while small jails will be excluded. Accordingly, there are a
total of 22 main prisons (11 matched pairs) eligible for the study in which the five
matched pairs are in Tigray and the remaining in the Amhara region. All the five
matched prison pairs from Tigray will be included in the randomization considering
their proximity and hence feasibility. However, the investigators will undertake a
random selection and will include three matched pairs from the Amhara region
considering the feasibility and financial constraints.
3.3. Randomization
Once the required number of matched prisons pairs was fixed, the randomization was done
within pairs in which eight prisons from each pair were randomly assigned to the
intervention and the remaining to the control group. One of the investigators from
Maastricht University who didn't have information about the study prisons performed the
randomization by consulting the online randomization website; random.org. The
investigators will then undertake follow-up and monitoring for a year (from March 2016
to April 2017) and outcomes will be measured 3.3.1. Procedure
After the investigators have had discussions and agreements with the concerned bodies
in the Amhara and Tigray regions, eligible prisons were selected according to our
inclusion criteria. Then the investigators matched the selected prisons into pairs
considering geographical location and/or the number of prisoners as described above.
After the number of the required matched pairs was fixed, the randomization was done to
the intervention and control group .
3.4. Interventions
3.4.1. Training inmate peer educators
Before launching the intervention program, the investigators will discuss the
objectives and procedures of the program with the prison administrators, the prison
health personnel, and the prisoners. Inmate peer educators, about 3-6 from each prison,
will be recruited in consultation with the prison health personnel. The investigators,
in collaboration with the prison health personnel, will provide 3 days training for
inmate peer educators using standard TB training materials. The training will focus on
basic facts about TB: its cause, transmission, symptoms, diagnosis, prevention,
treatment, and outcomes. Inmate peer educators will be trained on how to provide health
education about TB, screen and identify presumptive TB cases, and support TB patients
to adhere to the TB treatment. Moreover, inmate peer educators will be provided with
leaflets and posters illustrating the cause, transmission, main symptoms of TB, and
containing the information that TB is curable with proper treatment. Inmate peer
educators will also be informed to teach and encourage their fellow inmates about the
isolation of TB patients as much their setting allows.
3.4.2. Educating prisoners and performing TB screening
After the training, but before trained prison peer educators start their activities,
the investigators will assess whether inmate peer educators are really capable of doing
the expected activity. The investigators will make them teach a sample of trainees in
front of trainers and will evaluate inmate peer educators using a checklist. Inmate
peer educators will also be tested whether they are cable of identifying presumptive TB
cases by providing them presumptive TB cases and non-presumptive TB cases and verifying
their diagnosis by TB experts (trainers). Once they are tested for their capability,
peer educators will organize inmates into groups and will provide education about TB,
its prevention, and control every two weeks on a regular basis for one year. Peer
educators will undertake routine TB screening using a standardized TB screening
protocol to identify presumptive TB cases for a referral. Inmate peer educators will be
provided with N95 masks to be used during the screening. Identified presumptive TB
cases (those, at least, having had a cough for two weeks or more according to the
recommendation of national TB guideline) will be referred by the prison health
personnel to nearby hospitals.
3.4.3. Tuberculosis treatment follow-up
Trained inmate peer educators will follow and encourage their fellow patients to adhere
to the prescribed TB treatment and to undertake follow-up sputum examination according
to the national recommendation. Inmate peer educators will provide health education
about the consequences of nonadherence to TB treatment using the prepared TB training
module .
3.5. Control Conditions
At the control sites, there will not be involvement of inmate peer educators and no
training will be provided. The TB screening and treatment activity will follow the
existing referral system (self-referral to nearby hospitals). However, the prison
personnel at these sites will be informed about the proposed intervention. The prison
personnel will be informed that this is a trial and that the investigators don't know
whether the intervention is effective or not. The investigators will also inform the
prison personnel that other prison sites were selected by chance and the intervention
will be implemented in the control prisons if the investigators found this trial
effective and helpful. Moreover, the investigators will provide a standardized
up-to-date referral protocol to the prison personnel at the control sites as in the
intervention sites.
3.6. Follow-up and monitoring
Supervisors assigned to each intervention site (prison) will regularly follow the
intervention progress, do a daily assessment of the activities and give a timely
solution to the problems met. The principal investigator will also supervise all
activities closely through a regular visit and phone call. Randomly selected prisoners
from each intervention site will be asked short random questions to check whether they
did get the intervention or not at random times during the intervention.
An intervention check will also be done by collecting data on knowledge attitude and
practices (KAP) of prisoners in the intervention sites using a standardized pre-tested
KAP questionnaire through a face-to-face interview by trained prison nurses. Inmate
peer educators will be involved in facilitating and interviewing of the baseline data,
but the post-test will be performed by trained nurses only. Briefly, the KAP
questionnaire will consist of questions on the etiology of TB, mode of transmission,
prevention and on attitudes of prisoners such as whether they are afraid to get
infected with TB bacilli or not. A sample of prisoners will be selected randomly with
proportional allocation of the total number of prisoners in each intervention site and
data on their KAP score will be assessed at baseline and the end of the intervention
(after 12 months). Only prisoners that will be available in prisons during the
intervention period will be eligible for the random selection. Finally, data will also
be collected from the randomly selected prisoners from the control sites and the KAP
scores of the two groups will be compared.
Supervisors will also be assigned for each control site. They will neither encourage
nor discourage the existing TB diagnosis and treatment program in these sites. But,
supervisors will regularly follow the ongoing activities with equal frequency as in the
intervention sites. The principal investigator will also supervise all activities
closely through a regular visit and phone call.
3.6.1. Contamination check
Together with the supervisors, the principal investigator will undertake a random
assessment at the control sites regularly every week throughout the intervention period
to check whether some sort of new TB control methods or peer education has been started
in the control sites as in the intervention sites. Then,the investigators will give
timely solutions if possible or will consider the contamination during result
interpretation.
3.7. Blinding
Neither the prison health personnel nor peer educators will be blinded to the
allocation. However, the data analyzer and the laboratory personnel will be blinded.
3.8. Demographic and clinical data collection
Demographic and clinical information such as pre-treatment symptom duration will be
collected from TB confirmed cases detected at both the intervention and control sites
using a pre-tested structured questionnaire. Patients' sputum smear status, the
radiological findings and treatment outcomes will be recorded from the referrals sites
and Directly Observed Treatment Short Course (DOTS) centers in both groups. The
investigators will also collect data on the size of the prison cells and on the number
of pulmonary TB cases detected in the previous two years before the start of this
intervention in both the intervention and control sites to consider for possible
adjustments.
3.9. Laboratory Methods and Diagnostic criteria
For both the intervention and control conditions, TB diagnosis will be carried out at
the referral sites using the direct smear microscopy and/or chest X-ray (the routine
available diagnostic methods). Three sputum samples (spot-morning-spot) will be
collected from each presumptive TB case and direct sputum microscopy will be performed
using Ziehl-Neelsen staining technique as per the national guideline at the referral
sites by experienced laboratory technologists. Chest X-ray will also be performed at
referral sites. A presumptive TB case with one or more initial sputum smear
examinations (direct smear microscopy) AFB-positive; or one sputum examination
AFB-positive plus radiographic abnormalities consistent with active pulmonary TB as
determined by a clinician will be considered as a smear-positive TB case according to
the national guideline [24]. A patient having symptoms suggestive of TB with at least 3
initial smear examinations negative for AFB by direct microscopy, and with no response
to a course of broad-spectrum antibiotics, and with radiological abnormalities
consistent with pulmonary tuberculosis will be considered as a smear-negative pulmonary
TB case [24]. All confirmed TB cases will be treated according to the national
guideline. The treatment regimen for new TB cases consisted of two months intensive
phase treatment with ethambutol, rifampicin, isoniazid and pyrazinamide followed by a
continuation phase treatment for 4 months with isoniazid and rifampicin. Follow-up
sputum examination will be conducted according to the national recommendation and
outcomes (treatment success, failure, default, and death) will be recorded by the data
collectors (trained prison nurses). A smear-positive TB patient with at least two
negative smears including the last month of treatment will be reported as cured. A
patient who finished the treatment but did not have a smear result in the last month of
treatment and on at least one previous occasion will be reported as treatment
completed. If a patient remained or became smear-positive at the end of 5 months or
later, he/she will be reported as treatment failure. A patient who missed treatment for
eight consecutive weeks after receiving treatment for at least 4 weeks will be reported
as a defaulter. A patient who was transferred to another recording and reporting unit
after receiving treatment for at least 4 weeks and whose treatment outcome was not
reported to the referring district will be reported as transferred out. A patient who
died while on treatment will be reported as dead irrespective of the cause of death
[25].
3.10. Sample size calculation
The number of pair-matched clusters required for this study was determined using a
formula suggested by RJ Hayes and S Bennett [26] for a pair-matched cluster randomized
trials of unequal cluster size as shown below. The sample size was calculated based on
the following assumptions: an estimated average annual pulmonary TB case detection rate
(CDR) of 40% in the study prisons (estimated using unpublished review of the two years
DOTs record from some study prisons), expecting to detect a 50% increment in case
detection rate over the intervention period (from 40% in the control groups to 60% in
the intervention groups), a power of 80%, a coefficient of variation of 0.25, and a
significance level of 0.05. The number of clusters was fixed considering only the
primary outcome (case detection rate). A coefficient of variation of 0.25 was
considered since there was no full data for the matched prison pairs to calculate the
exact value.
C = 2+ (Zα/2 + ZB) 2 [X0 x Av (1/X0j) + X1 x Av (1/X1j) + K2 (X02 + X12)]/ (X0-X1)2
Where:
C = number of matched clusters Zα/2 = level of significance, 95% = 1.96 Zβ = power of
the study, 80% = 0.84 X0 = the estimated average annual smear-positive case detection
rate in the control sites = 40% X1 = the estimated average annual smear-positive case
detection rate in the intervention sites = 60% K= coefficient of variation = 0.25 Av
(1/X0j) = the mean of the reciprocals of the cluster sizes (person-years) in the
control group = 0.001 Av (1/X1j) = the mean of the reciprocals of the cluster sizes
(person-years) in the intervention group = 0.0014 This computation provides a cluster
size of 8.6 pairs. Considering feasibility, the investigators chose 8 pairs.
3.11. Study variables
3.11.1. Outcome variables
The primary outcome measure for this study is case detection rate while treatment
outcome (success, failure, death) and pre-treatment symptom duration are the secondary
outcomes of interest. Moreover, the investigators will also compare the KAP scores of
the two groups at the end of the intervention.
Case detection rate (CDR): Calculated as notifications of new and relapse cases divided
by the estimated incidence per year. The mean CDR will be compared within each pair at
the end of the intervention (after 12 months).
Treatment success rate (TSR): Cure or treatment completion rate will be calculated as
the number of patients cured or treatment completed divided by the total number of
patients reported expressed as a percentage. Treatment success rate is the sum of cure
and treatment completion rate.
Pre-treatment symptom duration: Measured as the proportion of patients with
pre-treatment symptom duration of >=3 months vs. < 3 months.
3.11.2. Predictor variables
- The presence/absence of the intervention
- Socio-demographic characteristics (age, sex)
- Seasonal variations (spring, winter, autumn, summer) 3.12. Operational definitions
Jail: A facility that is used to temporarily detain those who are suspected or
convicted of a crime.
Inmate/prisoner: Somebody confined in a prison as a punishment for a crime or while
waiting to stand trial.
Peer education: The teaching or sharing of health information, values, and behavior in
educating others who may share similar social backgrounds or life experiences.
Prison: A facility that holds convicts who have committed crimes the legal system deems
especially serious for more long term sentences.
3.13. Plan for Analysis
Collected data from questionnaire and laboratory analysis will be checked for
completeness before entry to a database. The data will be entered using Epi Data entry
version 3.1 software. Frequency analysis will be run to look into the range of values,
identify missing data or possibly miscoded data. Then we will use SPSS 20.0 for Windows
for analysis as recommended for a cluster level analysis (matched analysis).
Considering prisons as a unit of analysis, the mean CDR, TSR and percentage of patients
symptomatic for > 3 months will be compared within pairs using the paired t-test or
sign test as appropriate. The investigators will also perform analysis by date to see
the trends of the outcome measures over the intervention period.
3.14. Quality assurance methods
The questionnaire will be pre-tested to ensure its reliability and validity. Inmate
peer educators will be thoroughly trained in TB screening procedures and treatment
supervision. The supervisors assigned to each prison alone, or with the principal
investigator, will supervise the activities, do a rapid assessment of the general
activities, and give a timely solution to the problems met. Experienced laboratory
professionals will be involved in the microscopic examination and quality control of
the slides examined will be ensured at regional laboratories in each region.
3.15. Ethical Consideration
Ethical clearance will be taken from Ethical Review Committees of Mekelle University. A
written co-operating letter will be taken from the prison- administrators of each
region. The participants will be included in the study after they have provided written
informed consent. Patients who are confirmed to have tuberculosis will be referred to
get treatment. The confidentiality of both paper-based and electronic patient data will
also be safeguarded throughout the research activities and even after the research is
completed.
3.16. Dissemination of the results
Once analyzed and written up, the findings of the study will be submitted to Mekelle
University, Maastricht University, Federal Ministry of Health and other potential
partners. Moreover, key findings of the study will be presented at scientific meetings
and conferences so as to lobby for a reformulation of national TB control policy with
the necessary attention given in such settings. The written manuscript will also be
submitted to peer-reviewed journals for publication.
4. Trail registration The protocol of this clinical trial will be registered at
Clinicaltrials.gov website.