Tuberculosis
Conditions
Brief summary
To compare treatment success (adherence and completion of treatment) and safety of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB.
Detailed description
Tuberculosis (TB) is the leading infectious killer globally and a major cause of illness and suffering. The World Health Organization has prioritized TB preventive therapy (TPT) for people with latent TB infection (LTBI) as a key strategy for controlling the epidemic. Prevention of TB with isoniazid preventive therapy (IPT) is effective and reduces morbidity and mortality, and has been the mainstay of TB prevention for decades. But for an intervention with an excellent evidence of efficacy, global uptake has been abysmal. Completion rates for IPT when it is administered are poor (Gillespie 2008; Durovni 2010), with a large proportion of patients unable to complete treatment (McClintock 2017; Sterling 2011). While uptake is influenced by a variety of factors, a critical element has been the duration of IPT, with adherence falling sharply over time in clinical trials and practice. Shorter course regimens have a much higher completion rate and are more acceptable to patients, clinicians, and programs.
Interventions
DRUGRifapentine 600 mg and INH 300 mg
Participants will receive Rifapentine 600 mg and INH 300 mg
DRUGRifapentine 900 mg and INH 900 mg
Participants will receive Rifapentine 900 mg and INH 900mg
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Sanofi
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Arm A (n=250): Experimental arm. Rifapentine 600 mg daily and isoniazid 300 mg daily for 4 weeks. Arm B (n=250): Control arm. Rifapentine 900 mg and isoniazid 900 mg weekly for 12 weeks.
Eligibility
Sex/Gender
ALL
Age
15 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Positive tuberculin skin test or interferon-gamma release assay (IGRA) test and * Household contact of an infectious TB case within previous 90 days, defined as sleeping at least once in a residence with a person diagnosed with pulmonary TB, or * Documented conversion of Tuberculin skin test (TST)/IGRA from negative to positive within 2 years
Exclusion criteria
* Documented HIV infection * Evidence of active tuberculosis on clinical exam or chest x-ray * Known intolerance of any study drug * Treatment for active or latent TB in the past for more than 14 days * Known close contact to someone with INH or rifampin resistant TB * Active liver disease or Aspartate aminotransferase(AST)/Alanine transaminase (ALT) \>3 times upper limit of normal (ULN) * Neutropenia (ANC \<1000) * Peripheral neuropathy \>Grade 1 by DAIDS Grading Table * Pregnant or breastfeeding. Women of childbearing potential must agree to use non-hormonal contraception during study treatment. * Weight \<40 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Complete Treatment With >90% Adherence | 6 months | To compare treatment success (completion of treatment with \>90% adherence) of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB. |
| Frequency of Targeted Adverse Events or Treatment Discontinuation for Side Effects | 6 months | Participants with targeted adverse event grade 2 or more or discontinuing treatment for any side effect. |
Countries
Brazil
Participant flow
Pre-assignment details
531 people signed consent to be screened for eligibility. 31 people did not meet the eligibility criteria. The reasons were: Risk for Bad Outcome n=8, Active TB n=5, Withdrew Consent n=3, Pregnant n=1, Neutropenia n=2, AST/ALT \> 3 times ULN n=8, HIV infection n= 1, Drug-Drug Interaction n=2, Past TB-TPT treatment n=1. 500 people were assigned to a treatment group in the study. 249 were Randomized to Arm A:1HP. 251 were randomized to Arm B: 3HP
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 1HP Participants will receive Rifapentine 600 mg daily and isoniazid (INH) 300 mg daily for 4 weeks.
Rifapentine 600 mg and INH 300 mg: Participants will receive Rifapentine 600 mg and INH 300 mg | 249 |
| Arm B: 3HP Participants will receive Rifapentine 900 mg and isoniazid 900 mg weekly for 12 weeks.
Rifapentine 900 mg and INH 900 mg: Participants will receive Rifapentine 900 mg and INH 900mg | 251 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 7 |
| Overall Study | Index INH Resistant | 0 | 1 |
| Overall Study | Lack of Efficacy | 6 | 18 |
| Overall Study | Lost to Follow-up | 6 | 12 |
| Overall Study | Moved | 0 | 2 |
| Overall Study | Physician Decision | 3 | 0 |
Baseline characteristics
| Characteristic | Arm A: 1HP | Total | Arm B: 3HP |
|---|---|---|---|
| Age, Continuous | 40 years | 39 years | 38 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 61 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 141 Participants | 296 Participants | 155 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 140 Participants | 70 Participants |
| Region of Enrollment Brazil | 249 Participants | 500 Participants | 251 Participants |
| Sex: Female, Male Female | 167 Participants | 307 Participants | 140 Participants |
| Sex: Female, Male Male | 82 Participants | 193 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 249 | 0 / 251 |
| other Total, other adverse events | 13 / 249 | 10 / 251 |
| serious Total, serious adverse events | 1 / 249 | 2 / 251 |
Outcome results
Primary
Frequency of Targeted Adverse Events or Treatment Discontinuation for Side Effects
Participants with targeted adverse event grade 2 or more or discontinuing treatment for any side effect.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: 1HP | Frequency of Targeted Adverse Events or Treatment Discontinuation for Side Effects | 40 Participants |
| Arm B: 3HP | Frequency of Targeted Adverse Events or Treatment Discontinuation for Side Effects | 26 Participants |
Primary
Number of Participants Who Complete Treatment With >90% Adherence
To compare treatment success (completion of treatment with \>90% adherence) of 1HP with 3HP in HIV-uninfected adults and adolescents at increased risk of TB.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: 1HP | Number of Participants Who Complete Treatment With >90% Adherence | 223 Participants |
| Arm B: 3HP | Number of Participants Who Complete Treatment With >90% Adherence | 211 Participants |
p-value: 0.07Chi-squared, Corrected