Treatment of Latent TB Infection for Jailed Persons
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Laboratory Test or Clinical Judgment Resulting in the Need to Stop Study Medication [up to one year]
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 [course of treatment]
- Cost Effectiveness [course of treatment]
Eligibility Criteria
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:
-
history of treatment-limiting reaction to isoniazid or rifamycins;
-
pregnancy or breast feeding;
-
active tuberculosis;
-
an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the upper limit of normal;
-
bilirubin >2 times the upper limit of normal;
-
platelets <150 K/mm3;
-
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco | San Francisco | California | United States | 94143-0608 |
Sponsors and Collaborators
- University of California, San Francisco
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Mary C White, PhD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 03-135
- U01AI051315
Study Results
Participant Flow
| Recruitment Details | Inmates in the San Francisco City and County Jail diagnosed with latent tuberculosis infection (LTBI) at jail entry were recruited,consented and enrolled between 11/30/2004 and 9/24/2007. |
|---|---|
| Pre-assignment Detail | Of 416 inmates with LTBI who consented to be enrolled, 52 were not randomized because of abnormal liver function tests (20), they were released before they could be assigned to a group (30), or they subsequently changed their mind and refused participation (2). |
| Arm/Group Title | Isoniazid | Rifampin |
|---|---|---|
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months |
| Period Title: Overall Study | ||
| STARTED | 184 | 180 |
| COMPLETED | 47 | 60 |
| NOT COMPLETED | 137 | 120 |
Baseline Characteristics
| Arm/Group Title | Isoniazid | Rifampin | Total |
|---|---|---|---|
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months | Total of all reporting groups |
| Overall Participants | 184 | 180 | 364 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
183
99.5%
|
180
100%
|
363
99.7%
|
| >=65 years |
1
0.5%
|
0
0%
|
1
0.3%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
30.34
(9.59)
|
31.51
(9.57)
|
30.9
(9.59)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
11
6%
|
14
7.8%
|
25
6.9%
|
| Male |
173
94%
|
166
92.2%
|
339
93.1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
184
100%
|
180
100%
|
364
100%
|
Outcome Measures
| Title | Number of Participants With Laboratory Test or Clinical Judgment Resulting in the Need to Stop Study Medication |
|---|---|
| Description | 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. |
| Time Frame | up to one year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants was determined by power calculations using estimates of toxicity from the literature. The analysis was intention to treat. |
| Arm/Group Title | Isoniazid | Rifampin |
|---|---|---|
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months |
| Measure Participants | 184 | 180 |
| Number [participants] |
6
3.3%
|
3
1.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Isoniazid, Rifampin |
|---|---|---|
| Comments | The null hypothesis was that there would be no difference in toxicity by study group, and a sample of 360 participants (180 in each group)was estimated to have sufficient power to detect a difference. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >.05 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | .51 | |
| Confidence Interval |
() 95% .13 to 2.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Completion of Therapy |
|---|---|
| Description | |
| Time Frame | course of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Isoniazid | Rifampin |
|---|---|---|
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months |
| Measure Participants | 184 | 180 |
| Count of Participants [Participants] |
47
25.5%
|
60
33.3%
|
| Title | Cost Effectiveness |
|---|---|
| Description | |
| Time Frame | course of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cost effectiveness data were not collected. |
| Arm/Group Title | Isoniazid | Rifampin |
|---|---|---|
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | Adverse events were collected during the course of treatment for each participant, until treatment was completed or subject was lost or withdrawn from the study. This was up to 1 year for all participants. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Participants had routine blood tests for liver functions and clinical review for symptoms at regular intervals during receipt of the study medication. While they remained in jail, adverse events also were collected for all sick call visits to jail health personnel. | |||
| Arm/Group Title | Isoniazid | Rifampin | ||
| Arm/Group Description | isoniazid (INH) (900 mg orally) given twice weekly for 9 months | rifampin (600 mg orally) given daily for 4 months | ||
All Cause Mortality |
||||
| Isoniazid | Rifampin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Isoniazid | Rifampin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/184 (6%) | 3/180 (1.7%) | ||
| General disorders | ||||
| allergic reaction | 0/184 (0%) | 0 | 1/180 (0.6%) | 1 |
| Hepatobiliary disorders | ||||
| elevated liver function test | 8/184 (4.3%) | 8 | 1/180 (0.6%) | 1 |
| Psychiatric disorders | ||||
| suicidal thoughts | 1/184 (0.5%) | 1 | 1/180 (0.6%) | 1 |
| Surgical and medical procedures | ||||
| hospitalization for ankle surgery | 1/184 (0.5%) | 1 | 0/180 (0%) | 0 |
| hospitalization for appendectomy | 1/184 (0.5%) | 1 | 0/180 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Isoniazid | Rifampin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 46/184 (25%) | 45/180 (25%) | ||
| Gastrointestinal disorders | ||||
| gastrointestinal symptoms | 12/184 (6.5%) | 10/180 (5.6%) | ||
| Hepatobiliary disorders | ||||
| elevated liver function tests | 12/184 (6.5%) | 8/180 (4.4%) | ||
| Injury, poisoning and procedural complications | ||||
| injury | 9/184 (4.9%) | 11/180 (6.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| skin rash | 13/184 (7.1%) | 16/180 (8.9%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mary White |
|---|---|
| Organization | University of California, San Francisco |
| Phone | 415-476-5213 |
| mary.white@nursing.ucsf.edu |
- 03-135
- U01AI051315