Clinical trial NCT00128206: Treatment of Latent TB Infection for Jailed Persons
Official title: Clinical Trial of Short Course Rifampin Versus INH for LTBI in Jail
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tuberculosis
Keywords: LTBI, tuberculosis, rifampin, isoniazid, prisoners
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2005-08-09
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Laboratory Test or Clinical Judgment Resulting in the Need to Stop Study Medication
timeFrame: up to one year
Secondary outcomes:
measure: Completion of Therapy
timeFrame: course of treatment
measure: Cost Effectiveness
timeFrame: course of treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Mary C White, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: White MC, Tulsky JP, Lee JR, Chen L, Goldenson J, Spetz J, Kawamura LM. Isoniazid vs. rifampin for latent tuberculosis infection in jail inmates: toxicity and adherence. J Correct Health Care. 2012 Apr;18(2):131-42. doi: 10.1177/1078345811435973. Epub 2012 Mar 14.