Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00939419 |
| Other study ID # |
3140-ET |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
July 14, 2009 |
| Last updated |
July 15, 2009 |
| Start date |
January 2005 |
| Est. completion date |
February 2007 |
Study information
| Verified date |
July 2009 |
| Source |
University of Leeds |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Ethiopia: Ethical Review Committee |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of the study is whether the provision of tuberculosis care using volunteer
community health workers or self-administered treatment for 7 months is equally effective
with the existing 8 months of TB care in public health facilities by health workers. Patient
care by volunteer community health workers and 7 months of self-administered treatment are
more patient-convenient delivery options than the ongoing TB care in health facility.
Description:
Study setting
The study will be conducted in 10 districts which fully implemented the DOTS program in all
their health facilities in order to determine whether better patient quality of care and
convenience using three TB care options could improve treatment outcome. In the study
districts there are 149 tabias and 1163 kushets with 1.2 million residents representing 30%
of the total population of the region. All public health facilities (8 hospitals, 11 health
centres and 48 health posts) in these districts will be included. District hospitals and
health centres provide TB diagnostic services. The study districts comprise 2316 volunteer
community health workers (CHWs) who are functional and accountable to the public health
system.
Study population
Patients will be recruited from the 10 study districts of all public health institutions
which serve both urban and rural population. New patients diagnosed in the study districts
(8 hospitals and 10 of the health centres) and those referred for treatment will be
included. Patients suspected of pulmonary tuberculosis (PTB) disease will be diagnosed based
on the following case definitions:
1. A patient with at least one of the following criteria will be diagnosed as smear
positive PTB:
1. Two initial smear examinations positive by direct microscopy for acid-fast bacilli
(AFB) or,
2. One initial smear examination positive by direct microscopy and culture positive,
or
3. One initial smear examination positive by direct microscopy and x-ray
abnormalities suggestive of active TB as determined by the physician.
2. A patient is diagnosed as smear negative PTB when three initial smear examinations were
negative by direct microscopy for AFB, and there was failure to respond to a course of
broad-spectrum antibiotics followed by there were three negative smear examinations and
x-ray abnormalities suggestive of active TB as determined by the treating physician.
Both smear positive (PTB+) and smear negative pulmonary (PTB-) patients will be recruited to
increase the generalizability of the study.
Pre-trial measures
Interventions to improve the quality of TB care
Baseline studies were conducted to determine the quality of TB diagnosis, patient care and
treatment outcome and to identify alternative options TB care appropriate to local
conditions. Six months prior to the trial, the limitations of the ongoing DOTS found by
these studies were communicated to district health office heads, hospital directors and
district TB experts in order to strengthen the quality of TB care and management of district
TB programs. Specific tools that were not developed by the National Tuberculosis Program
(NTC) to ensure consistent application of diagnostic criteria, patient counselling/health
information, standards on supervisory support, drug supply and district evaluation were
prepared in consultation with district health management experts and hospital directors.
Subsequently, district TB coordinators, health institution-based TB focal persons and
clinicians were trained on patient diagnosis, patient care, community-based tuberculosis
care and the study protocol. Based on our baseline assessment of quality of care, the
following measures which improve patient-centred care were instituted at health facility
level:
1. Quality control measures to improve the quality of diagnosis.
2. Definition of what health information should be conveyed to patients,
3. Patient teaching using a one to one interactive counselling method.
4. Training of health workers in TB management (TB focal person) with particular emphasis
on patient management, management of drug side effects and interpretation of treatment
outcome, and reporting.
5. Treatment in patients' most convenient health facilities.
6. Provision of daily out patient TB services in health facilities.
7. Continuous support by health workers or CHWs with a workable referral system.
Tuberculosis treatment registers were translated into the local language and were modified
to fit with the monitoring and interpretation of treatment outcomes at health facility level
for patients in the three treatment groups. Volunteer CHWs were also trained by their nearby
health institution TB focal person on patient care, drug handling, indications for referral,
managing side effects, and the use of the patient adherence card. Quarterly supervisory
support was given by regional experts to district health offices, while health institutions
were supervised on a monthly basis by district TB coordinators. The nearby TB focal person
provided technical support to volunteer CHWs during their monthly meeting in the respective
health facilities. Biannual evaluation between district health staff with HQ staff and
district health staff with TB focal persons were instituted. The implementation of the above
measures prior to the launching of the trial created 'operational conditions' of components
of the strategy as recommended by the NTC and International Union against Tuberculosis and
Lung disease (IUTL)/WHO (Wold Health Organisatio) guidelines. Strengthening the health
system based on local conditions is assumed to be a basis for determining specific needs,
and for creating the conditions for the development of the necessary managerial and
technical skills for effective implementation of a community-based TB care.
Selection of delivery options for TB care
Four prominent TB care delivery options were identified from our community based survey:
Volunteer CHWs, Public health workers, Self-administered treatment and Family member.
Further assessment regarding their reliability and implications for the DOTS strategy was
made using the following selection criteria:
1. Uninterrupted supply of anti-TB drugs to patients could be ensured,
2. Quality of care comparable to the prevailing health facility based TB care could be
instituted,
3. Accountability in terms of guaranteeing proper use of drugs and monthly reporting of
treatment outcomes of patients to the public health system,
4. Feasibility in terms of cost when applied on a larger scale and,
5. Level of acceptance by local communities as determined from our cross-sectional study.
In addition to the prevailing health facility-based TB care, the use of volunteer CHWs and
self-administered treatment were found to be appropriate options for pilot testing. Based on
our criteria, care by family members had the least operational feasibility because the costs
involved to families (labour cost from interruptions of daily activities and transport cost)
and the health systems (health worker time and cost of training) could be high. Operational
difficulties were also anticipated in setting up an appropriate system for monitoring of
anti-TB drugs used, provision of health education, referral, monthly reporting of treatment
outcome particularly among family members who could be in remote parts of the region.
The decentralization of TB care at community level using the existing volunteer CHWs program
was anticipated to be a feasible option to institute most of the components of the
WHO-recommended DOTS strategy. Volunteer CHWs can be trained in patient care on a continuous
basis. Accountability on anti-TB drugs used and reporting on treatment outcomes can be
obtained using the existing link between CHWs and nearby public health facilities. The
services they render are appreciated by respective communities. The self-administered
treatment option was considered after critical examination of previous effectiveness
studies, patients' convenience to tuberculosis care and, most importantly, taking into
account the views expressed by communities and patients. Operational challenges, in which
health workers could be forced to allow patients to take treatment by themselves when there
are no volunteer CHWs who could offer TB care in remote areas was also considered.
Defining intervention arms
The final step was how optimal quality of TB care with less inconvenience could be reached
among the two alternative options from patients' perspective in order to achieve optimum
treatment outcome target. These integrated interventions were therefore targeted to test
treatment outcome by instituting both a comparable patient quality care and patient
convenience to TB care among the three strategies. In order to do this three factors were
considered.
1. Epidemiological factors From the baseline study, most patients do not interrupt
treatment during the intensive phase of treatment. But, the occurrence of death is high
during the first 2 months of treatment. Even though its contribution is unknown in
Ethiopia, the high HIV-TB co-morbidity and mortality during anti-TB therapy has been
attributed in other sub-Saharan countries. Thus, proper management in health facilities
during the first 28 days for patients assigned into volunteer CHW care or
self-administered groups would ensure their health care needs.
2. Operational factors The intervention was designed to be implemented under operational
conditions of the district health system and the ongoing community-based volunteer CHW
programme. CHWs get technical and material support form nearby health facilities. They
are required to submit their activity report at these facilities on a monthly basis.
This arrangement has been found effective in maintaining the functionality of CHWs
while minimizing disruptions in their daily life. Given this operational condition,
patients have to be managed in nearby health facilities for the first four weeks until
proper selection and introduction with respective CHWs are made. Other operational
factors in favour of this arrangement include its feasibility when scaling up the
intervention, low time cost of CHWs and the health system. This operational set up was
anticipated to enable TB focal persons to organize a monthly evaluation session with
CHWs in their catchments.
3. Ethical issues Health interventions should be safe and minimize potential risks leading
to patient morbidity and mortality. In Ethiopia a significant proportion of
tuberculosis patients are also infected with HIV. The fact that assigning such patients
into an intervention whose effectiveness is unknown (volunteer CHWs) or allowing them
to die (self-administer group) was also regarded as unethical.
Interventions
Accordingly, all patients should receive daily TB care including observed daily doses of
treatment for the first 28 days from the most convenient health facility. Patients have to
be properly counselled about their illness and managed accordingly by the TB focal persons.
Counselling should be conducted using a standard procedure developed from our baseline
studies in order to ensure good quality of tuberculosis care. They should be taught
specifically on the causes and prevention of TB, side effects of drugs, treatment adherence
and the schedule for follow up examinations. During this time, the TB focal persons need to
assist patients to select volunteer CHWs from their village. They should explain their role
and created confidence between them. All eligible patients should be treated using anti-TB
drugs recommended by the national tuberculosis control of Ethiopia. PTB+ patients should
receive weight adjusted Ethambutol (E), Rifampicin (R), Isoniazid (H) and Pyrazinamide (Z)
during the first 8 weeks of treatment followed by 6 months of EH, while PTB- should be
treated with weight adjusted RHZ for two months, followed by 6 months of EH.
Patients assigned to the health worker-TB care group (HW-TC) should be followed as per the
national TB guideline, i.e. daily care including observed treatment by the TB focal persons,
in their respective nearby health institutions during the first 8 weeks followed by
self-administered treatment for the remaining 6 months. During the continuation phase
patients are expected to visit their nearby health facility every month for follow up.
Supervisory support will be given to TB focal persons by the respective district TB
coordinators on a monthly basis. Anti-TB drugs will be delivered to health institutions on a
quarterly basis by district TB coordinators during supervision.
Patients assigned to the volunteer CHW-TB care group (CHW-TC) should have daily TB care by
the CHWs in their villages for the second month followed by a monthly visit to the CHWs'
home for the remaining 6 months of self-administered treatment. Patients are expected to
visit health facility at the end of the second months and the end of treatment for sputum
examination. Technical support and anti-TB drugs should be given to CHWs by TB focal persons
every fortnight.
Those assigned to the self-administered treatment group (SA-TC) should take their medication
at home for seven months. They should be taught by the TB focal person to collect their
anti-TB drugs fortnightly and report missed daily doses. Follow up assessment and continued
support should be made by TB focal persons on a monthly basis in their nearby health
facility. Patients should also be told to report when they encountered severe side effects.
Procedures
A randomized controlled design will be used to compare the existing HW-TC with CHW-TC and
self-administered treatment. Eligible PTB+ and PTB- patients should be assigned using random
numbers, computer generated by a statistician at regional level. To avoid disproportionate
allocations among treatment groups two separate random blocks of 3 for PTB+ and PTB- are
arranged. Two sets of sequentially numbered sealed envelopes for each district will be
prepared. Two separate boxes containing sealed envelopes for PTB+ and PTB- will be given to
the head of each district health office. The district recruiting officers should obtain the
allocation arm for each patient from these district health office heads. For each district,
allocation codes used should be recorded weekly by telephone. A statistician will monitor
the quality of assignment by cross checking the original list in the research HQ with the
sequence of patients' attendance for recruitment. Recruiting officers will be trained using
a pre-tested guideline prepared to ensure that standard procedures are applied consistently
in screening and informing patients. Written consent should be obtained from every patient
following proper counselling, with particular emphasis on tuberculosis treatment and the
alternative options of care. Patients who refused the randomly assigned method of TB care
should be allowed to select either of the two remaining care options.
A request for a haemoglobin test from every eligible patient should be made by the health
facility TB focal person in the diagnostic health facilities (hospitals and health centres)
in order to collect serum for anonymous HIV testing before patients are sent to the district
recruiting officer. Laboratory technicians should send 5 cc of serum labelled by a coding
system developed by the Regional Research Laboratory (RRL) in the HQ. HIV test (Determine®
HIV-1/2, Abboti Laboratories) results should be made available to the research team at the
end of the trial. Baseline data should be collected from each eligible patient before he/she
is referred to the most convenient health facility. Patients are only identified by code
numbers in order to maintain confidentiality about their assignment. The codes should be
revealed to the study team after the preliminary data analysis and draft reporting phases
are completed.
Standard treatment outcome indicators developed by the WHO and the NTC will be used to
compare the effectiveness of the strategies. Treatment outcome data will be collected by a
team of three tuberculosis experts who are not involved in the study. Treatment outcome of
PTB+ patients should be assessed by sputum microscopy for the presence of acid fast bacilli
while clinical improvements and adherence to treatment will be used to assess the outcome of
PTB- patients by clinicians. Cure and treatment completion rates are used to compare
treatment groups. A patient is declared cured if confirmed to be sputum smear negative at
the end of treatment or one month prior to the completion of treatment and on at least one
previous occasion. A patient should be recorded as "treatment completed" if smear results
were not available on at least two occasions or has negative pre-treatment results. A
patient who has been on treatment for at least 4 weeks and whose treatment was interrupted
for more than 8 consecutive weeks or for a cumulative period of more than 12 weeks should be
classified as a defaulter and a patient who remains smear-positive at 5 months or later
during treatment should be considered to be a failure. A patient who had started treatment
for at least 4 weeks and had been transferred to another district should be recorded as
transferred out.
Statistical analysis
The comparative effectiveness of health workers-TB care to that of volunteer CHW-TC and
SA-TC in randomized control trials has never been reported so far. It is hypothesized that
no significant difference in cure and treatment completion rate among the three care groups
would be shown, taking the prevailing health facility-based TB care as the gold standard of
care. The sample size for PTB+ (179 patients per arm) was planned to detect at least a 10%
difference in treatment success rates between any of care groups (assuming 85% treatment
success rate in the highest arm and a baseline treatment success rate of 72%) with a power
of 80% at a significant level of 5%. With the same assumption (85% treatment completion rate
in the highest arm and a baseline treatment completion rate of 69%), all eligible PTB-
patients (131 patients per arm) should also be included during the study period. Separate
comparisons of effectiveness between the three methods of TB care will be carried out for
PTB+ and PTB- patients. Comparison of effectiveness of the care groups will be undertaken
according to the principle of intention-to-treat. The strength of association between
treatment outcomes and each care group will be determined using the chi-square test.
Adjusted effects of patients' characteristics, area of residence, HIV status, time elapsed
by each patient for treatment, the type of health facility and method of TB care used on
treatment outcomes will be computed using logistic regression analysis.
