Treatment of Latent TB Infection for Jailed Persons

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00128206
First received: August 5, 2005
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Drug: Isoniazid
Drug: Rifampin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Trial of Short Course Rifampin Versus INH for LTBI in Jail

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Number of Participants With Laboratory Test or Clinical Judgment Resulting in the Need to Stop Study Medication [ Time Frame: up to one year ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Completion of Therapy [ Time Frame: course of treatment ] [ Designated as safety issue: No ]
  • Cost Effectiveness [ Time Frame: course of treatment ] [ Designated as safety issue: No ]

Enrollment: 364
Study Start Date: November 2004
Study Completion Date: September 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
isoniazid (INH) (900 mg orally) given twice weekly for 9 months
Drug: Isoniazid
Isoniazid 900 mg twice weekly
Active Comparator: A
rifampin (600 mg orally) given daily for 4 months
Drug: Rifampin
Rifampin 600mg once per day

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128206

Locations
United States, California
University of California San Francisco
San Francisco, California, United States, 94143-0608
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Mary C White, PhD University of California, San Francisco
  More Information

No publications provided by University of California, San Francisco

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00128206     History of Changes
Other Study ID Numbers: 03-135, U01AI051315
Study First Received: August 5, 2005
Results First Received: September 21, 2010
Last Updated: May 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
LTBI, tuberculosis, rifampin, isoniazid, prisoners

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Isoniazid
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antimetabolites
Antitubercular Agents
Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Leprostatic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014