Treatment of Latent TB Infection for Jailed Persons

Tuberculosis Clinical Trial

Official title:

Clinical Trial of Short Course Rifampin Versus INH for LTBI in Jail

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00128206
• Other study ID #: 03-135
• Secondary ID: U01AI051315
• Status: Completed
• Phase: Phase 3
• Start date: November 2004
• Est. completion date: September 2009

Study information

• Verified date: July 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether an alternative drug, (rifampin) given daily, is better at treating tuberculosis (TB) and more tolerable than the usual drug treatment, isoniazid (INH). Study participants will include 972, TB infected, San Francisco Jail inmates, aged 18 or older. One group of volunteers will take INH two times a week for 9 months, and the other group will take rifampin daily for 4 months. Medication will be administered in jail and at the San Francisco TB Clinic if the volunteer is released from jail prior to completing the study. Participants will be seen daily for 4 months (rifampin group), and 2 times a week for 9 months (INH group) for directly observed therapy. Study procedures will include 5 symptom review visits and blood samples for lab testing. Follow-up will continue for each subject for five years after enrollment into the study.

Description:

The purpose of this project is to evaluate the effect of two accepted regimens for treating latent tuberculosis infection (LTBI) in jail. Tuberculosis (TB) in incarcerated populations continues to be a serious problem, due to the large proportion of persons who are at high risk of both having latent tuberculosis infection (LTBI) and developing active disease. Completion of treatment of LTBI, while an important component of overall TB control efforts, has not been successful in jails. This is primarily because inmates are frequently released before finishing a 6-9 month course of standard therapy, and have low rates of completing therapy in the community. This study proposes to look at toxicity and adherence for this 4-month regimen compared to the nine-month regimen of to isoniazid (INH), and to examine costs, both cost of delivered care and the cost of TB disease prevented, with examination of reasons for completion or noncompletion of therapy. Short-course therapies for LTBI may address this problem but they are more expensive and have not been studied adequately to answer questions about side effects, completion rates, and overall cost. The investigators propose a randomized trial to test the effects of a short course therapy, rifampin (600 mg orally) given daily for 4 months, as compared to (INH) (900 mg orally) given twice weekly for 9 months. Both regimens are listed by the Centers for Disease Control and Prevention (CDC) and the American Thoracic Society as acceptable treatments for persons with LTBI. The study participants will include 972 San Francisco Jail inmates, 18 years and older, enrolled over a 28-month period, for a sample of 486 in each study group. Subjects, followed in jail and after release, will be followed to test three hypotheses: the null hypothesis of a difference in toxicity of rifampin as compared to INH within a 95% confidence interval of (.4-1.87) and no difference by study group in adherence and in cost-effectiveness. A secondary aim is to describe reasons for completion or noncompletion of therapy. Toxicity is defined as complications leading to stopping drug. Adherence is defined as completion of care, or 120 doses taken within 6 months for the rifampin group and 76 doses of INH taken within 12 months for the INH group. Cost effectiveness will be calculated as the total cost of care (nursing, medical, laboratory, as well as facility costs), and measured against costs of TB cases prevented. All treatments will be administered by directly observed therapy (DOT) in jail, and by DOT after release at the San Francisco TB Clinic. Counseling on adherence (going to the TB Clinic if released before completing therapy) and on possible side effects will be given to all study subjects at enrollment and during follow-up clinic visits. All subjects will be routinely evaluated by study personnel every two weeks for the first 6 weeks, and thereafter to detect possible drug toxicity including hepatitis, peripheral neuropathy, arthralgias, rash, memory loss, and other clinical symptoms. All patients will undergo laboratory assessment at regular intervals according to a schedule which compares study group participation and the usual care in the jail. All blood test results, and new symptoms or changes in symptoms found at follow-up, will be added to the jail medical record. A final interview will be done with subjects at the time that they have completed or not completed this course of therapy for LTBI, to determine reasons (barriers and enablers). Follow-up will continue for each subject for five years after enrollment into the study, to measure study endpoint (completion of care, taken off drugs for toxicity or loss to follow-up) and to measure subsequent treatment for LTBI or development of active TB by record review.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: September 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

The inclusion criteria for this study will be San Francisco Jail inmates, age 18 or older (the jail does not house juveniles) having evidence of M. tuberculosis infection by positive tuberculin skin test (a documented reactive tuberculin skin test to 0.1 mL containing 5 Tuberculin Units) who meet current national criteria for therapy for tuberculosis infection and can provide informed consent.

Exclusion Criteria:

• Ineligible for either therapy regimen for any of the following reasons:

1. history of treatment-limiting reaction to isoniazid or rifamycins;

2. pregnancy or breast feeding;

3. active tuberculosis;

4. an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal;

5. bilirubin >2 times the upper limit of normal;

6. platelets <150 K/mm3;

7. taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs);

• Unable to communicate in English or Spanish;

• Unable or unwilling to provide informed consent;

• Not in the routine level of jail security for any reason (housed in "special security" areas);

• Any condition that, in the best judgment of the investigator, would pose a risk to the subject during the study.

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Drug:
• Isoniazid
Isoniazid 900 mg twice weekly
• Rifampin
Rifampin 600mg once per day

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Laboratory Test or Clinical Judgment Resulting in the Need to Stop Study Medication	Liver function tests were taken at regular intervals and clinical symptoms were reviewed at regular intervals in both study groups. On the basis of these tests and examinations, physicians determined whether the study drug needed to be stopped.	up to one year
Secondary	Completion of Therapy		course of treatment
Secondary	Cost Effectiveness		course of treatment