Clinical trial NCT00850915: Feasibility and Effectiveness of Community Based Isoniazid Preventive Therapy in Kenya
Official title: Feasibility and Effectiveness of Community Based Isoniazid Preventive Therapy in Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Tuberculosis
Keywords: tuberculosis
community IPT
isoniazid adverse events
tuberculosis incidence
Lead sponsor: KNCV Tuberculosis Foundation
Sponsor class: OTHER
Collaborators: name: Stichting Mondiale Tuberculose (SMT)
name: Kenya Medical Research Institute
name: Division of Leprosy Tuberculosis and Lung Disease, MOPHS, Kenya
name: Centres for Disease Control and Prevention, Kenya.
name: Ministry of Public Health and Sanitation, Kenya
name: Kenya National AIDS & STI Control Programme
First posted: 2009-02-25
Enrollment: 1259
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Isoniazid preventive therapy (IPT) is a well studied clinical intervention for primary and secondary prevention of active tuberculosis (TB) after infection with Mycobacterium tuberculosis. It is widely used in industrialized countries in TB outbreak management, focusing on high risk groups such as close contacts in the family, in congregate settings, and in the workplace amongst others. Individuals infected with Human Immunodeficiency Virus (HIV) have a markedly higher risk of acquiring a TB-infection and developing consequently active TB, making HIV-infected individuals a target population for IPT. Studies of IPT in HIV infected persons in the nineties demonstrated the efficacy of IPT in the prevention of active TB in Sub -Saharan Africa and more recent studies suggest that the protective effect remains present in individuals on antiretroviral therapy.

Despite the proven efficacy of IPT this intervention has not been taken up by most HIV and TB control programmes in Africa where the burden of TB/HIV is highest. The reasons for the low uptake of IPT are many and varied but include fears of expansion of isoniazid resistance and subsequently the development of multi -drug resistant TB with widespread use of IPT. Additionally screening protocols for excluding active TB and selecting persons for IPT have not been uniformly agreed upon. There have also been concerns that programmes designed to provide IPT may shift TB control programmes from their primary responsibility of finding and treating active TB. Finally it has been unclear as to which programme, between the HIV and the TB control programme, has the primary responsibility of managing the provision of the IPT intervention.

The World Health Organization and other technical agencies engaged in global TB control have recently re-emphasized the need to scale up IPT. In this proposal we outline an operational research study to evaluate the introduction of IPT at community level and to measure its effectiveness at preventing TB. The study is based on the context of expansion of Community-Based Direct Observed Therapy Short Course (CB-DOTS), home-based care and the concept of HIV prevention with positives (PwPs), where there is a real opportunity to focus on the household as a source of HIV-associated tuberculosis.

The study is designed as a cluster randomized trial. It compares the incidence of TB in household contacts including children under 5 of identified TB/HIV co-infected patients, who received IPT through proactive community intervention and those in a control group where the community was handled in the "usual way". In the intervention group household contacts of index cases of HIV positive, smear positive PTB will be visited at home and consenting contacts will be screened for active TB using a simple questionnaire. Those found to be fit will receive isoniazid 300mg (5 mg per Kg for children) once daily for 6 months, regardless of the HIV-status. Those found not to be fit will be referred for further evaluation at the nearest TB diagnostic centre. In the control group, routine care following national guidelines will be offered. This consists of contact invitation and assessment of eligibility for IPT, especially, in children less than 5 years. Both groups will be followed up monthly through household visits. Follow up will be for a total of 24 months including the six months when IPT is provided.

A confidential HIV screening test will be provided to all consenting contacts in both intervention and control group after appropriate counseling.

The primary outcome is the incidence of TB in the intervention and control household contacts. The difference in incidence between the two groups is a measure of efficacy of the intervention. In addition the efficacy of the intervention will be estimated stratified by HIV status of household contacts if data allows. Secondary outcomes are the incidence of adverse events, the incidence of TB-related symptoms, measures on the uptake of IPT (proportion of contacts starting and discontinuing IPT, treatment adherence) and programmatic indicators, i.e. percentage of persons eligible for IPT and resources needed.


Eligibility criteria: Index cases

* New sputum smear positive pulmonary tuberculosis (PTB) patients initiating treatment for TB
* HIV infected
* Resident in the catchment area of the TB diagnostic facility
* Written informed consent
* Age equal or greater than 15 years.

Contacts

* Household contacts of a HIV infected smear positive PTB
* No plans to relocate to another area for at least the next two years
* Asymptomatic (Fit) with no cough in last 2 weeks, fever, weight loss (or failure to gain weight in children), haemoptysis or chronic diarrhea at least for the last one month.
* Written informed consent

Primary outcomes:
measure: incidence of TB in household contacts
timeFrame: 12, 18, 24 months
Secondary outcomes:
measure: incidence of adverse events in household contacts
timeFrame: 12, 18, 24 months
measure: incidence of TB-related symptoms in household contacts
timeFrame: 12, 18, 24 months
measure: proportion of household contacts starting IPT
timeFrame: 12, 18, 24 months
measure: proportion of household contacts discontinuing IPT
timeFrame: 12, 18, 24 months
measure: proportion of household contacts adhering to IPT treatment
timeFrame: 12, 18, 24 months
Other outcomes:
Locations:
city: Makuyu-Muranga
country: Kenya
facility: Makuyu H/C
state: Central
city: Nairobi
country: Kenya
facility: Huruma Lions -Central district
state: Nairobi North
city: Nairobi
country: Kenya
facility: Kangemi HC
state: Nairobi North
city: Nairobi
country: Kenya
facility: Blue House, Mathare
state: Nairobi South
city: Nairobi
country: Kenya
facility: Jericho HC
state: Nairobi South
city: Nairobi
country: Kenya
facility: Kibera AMREF
state: Nairobi South
city: Nairobi
country: Kenya
facility: MMM, Mukuru, Embakasi
state: Nairobi South
city: Nairobi
country: Kenya
facility: Pumwani Majengo H/C
state: Nairobi South
city: Nairobi
country: Kenya
facility: Remand H/C
state: Nairobi South
city: Nairobi
country: Kenya
facility: Soweto Kayole, Embakasi
state: Nairobi South
city: Kapsabet-Nandi
country: Kenya
facility: KAPSABET District Hospital
state: North Rift
city: Kisumu district
country: Kenya
facility: NYALENDA
state: Nyanza North
city: Migori District
country: Kenya
facility: Kadem leprosy, Migori
state: Nyanza South
city: Migori District
country: Kenya
facility: Muhuru Health centre, Migori
state: Nyanza South
city: Rongo district
country: Kenya
facility: Awendo SDH
state: Nyanza South
city: Nakuru
country: Kenya
facility: Lanet
state: RVS
city: Nakuru
country: Kenya
facility: Nakuru West
state: RVS
city: Narok
country: Kenya
facility: Narok District Hosp
state: RVS
Study officials:
affiliation: Centre for Respiratory Diseases Research, Kenya Medical Research Institute
name: Jeremy M Chakaya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KNCV Tuberculosis Foundation, the Netherlands
name: Eveline Klinkenberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: