Treatment of Latent TB Infection for Jailed Persons
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Isoniazid; Rifampin
Intervention type(s): Drug; Drug
Intervention description(s): Isoniazid 900 mg twice weekly; Rifampin 600mg once per day
Intervention MeSH terms: Rifampin; Isoniazid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: LTBI, tuberculosis, rifampin, isoniazid, prisoners