Feasibility and Effectiveness of Community Based Isoniazid Preventive Therapy in Kenya

Tuberculosis Clinical Trial

— IPT  

Official title:

Feasibility and Effectiveness of Community Based Isoniazid Preventive Therapy in Kenya

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00850915
• Other study ID #: UR-01-2009-IPT-KENYA
• Status: Completed
• Phase: Phase 4
• First received: February 24, 2009
• Last updated: May 17, 2013
• Start date: April 2009
• Est. completion date: November 2012

Study information

• Verified date: May 2013
• Source: KNCV Tuberculosis Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Kenya: Kenya Medical Research Institute
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1259
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 15 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• community IPT
In the intervention group, the household contacts of enrolled TB/HIV co-infected patient are visited at home by community health workers. Those contacts providing informed consent and considered fit (assessed by simple questionnaire) are assumed not to have active TB and are eligible for IPT. They are offered isoniazid at 300mg (5 mg per Kg for children) once daily for 6 months, regardless of their HIV-status. In the control group, in line with routine care, eligible index cases are requested to send their contacts to the clinic for evaluation. Contacts presenting to the clinic will be screened for TB and receive IPT, if under 5 years and when active TB is ruled out as per the current national guidelines. All contacts (both intervention and control group) are followed up monthly to assess occurrence of symptoms suggestive of TB.

Locations

Country	Name	City	State
Kenya	KAPSABET District Hospital	Kapsabet-Nandi	North Rift
Kenya	NYALENDA	Kisumu district	Nyanza North
Kenya	Makuyu H/C	Makuyu-Muranga	Central
Kenya	Kadem leprosy, Migori	Migori District	Nyanza South
Kenya	Muhuru Health centre, Migori	Migori District	Nyanza South
Kenya	Blue House, Mathare	Nairobi	Nairobi South
Kenya	Huruma Lions -Central district	Nairobi	Nairobi North
Kenya	Jericho HC	Nairobi	Nairobi South
Kenya	Kangemi HC	Nairobi	Nairobi North
Kenya	Kibera AMREF	Nairobi	Nairobi South
Kenya	MMM, Mukuru, Embakasi	Nairobi	Nairobi South
Kenya	Pumwani Majengo H/C	Nairobi	Nairobi South
Kenya	Remand H/C	Nairobi	Nairobi South
Kenya	Soweto Kayole, Embakasi	Nairobi	Nairobi South
Kenya	Lanet	Nakuru	RVS
Kenya	Nakuru West	Nakuru	RVS
Kenya	Narok District Hosp	Narok	RVS
Kenya	Awendo SDH	Rongo district	Nyanza South

Sponsors (7)

Lead Sponsor	Collaborator
KNCV Tuberculosis Foundation	Centres for Disease Control and Prevention, Kenya., Division of Leprosy Tuberculosis and Lung Disease, MOPHS, Kenya, Kenya Medical Research Institute, Kenya National AIDS & STI Control Programme, Ministry of Public Health and Sanitation, Kenya, Stichting Mondiale Tuberculose (SMT)

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of TB in household contacts		12, 18, 24 months	No
Secondary	incidence of adverse events in household contacts		12, 18, 24 months	Yes
Secondary	incidence of TB-related symptoms in household contacts		12, 18, 24 months	No
Secondary	proportion of household contacts starting IPT		12, 18, 24 months	No
Secondary	proportion of household contacts discontinuing IPT		12, 18, 24 months	No
Secondary	proportion of household contacts adhering to IPT treatment		12, 18, 24 months	No