Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals

NCT03785106 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: HIV-NAT 255
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 16

Brief Summary

The investigators want to know if ultra-short, effective treatment for latent tuberculosis (TB) infection (LTBI) could dramatically reduce the global incidence of active TB or not. The investigators hypothesize that short-course (4-week) daily isoniazid/rifapentine (INH/RPT) (1HP) is not inferior to standard -course (12 weeks) INH/RPT weekly regimen (3HP) for the prevention of TB in human immunodeficiency virus (HIV)-infected individuals.

Conditions

HIV-infected Participants With Latent TB Infection in High TB Burden Country

Keywords

people living with HIV (PLHIV)

Outcome Measures

Primary Outcomes (4)

• efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study)

  proportion of participants that do not have active TB by the end of the study

  3 years

• safety of the regimens (proportion of participants that do not have any side effects throughout the study period)

  proportion of participants that do not have any side effects throughout the study period

  3 years

• tolerability to the regimens (proportion of participants that can complete the treatment course)

  proportion of participants that can complete the treatment course

  3 years

• prevalence of drug resistance of MTB

  proportion of participants with drug resistance to MTB

  3 years

Secondary Outcomes (19)

• severity of the condition

  3 years

• presence of symptoms

  3 years

• level of CBC

  3 years

• level of ALT

  3 years

• level of AST

  3 years

Study Arms (2)

1HP

EXPERIMENTAL

4-week daily regimen of weight-based RPT and INH, plus pyridoxine (vitamin B6)

Drug: Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)

3HP

ACTIVE COMPARATOR

12-weekly INH/RPT regimen, plus pyridoxine (vitamin B6)

Drug: Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)

Interventions

Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) DRUG

Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)

1HP

Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) DRUG

Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)

3HP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV-1 infection by standard HIV test or plasma HIV-1 RNA viral load and received ART within 12 months. Participants received ART more than 12 months would be allowed if CD4 cell counts is less than 350 cells/mm3
• years and older
• Evidence of latent TB infection, either by TST ≥5 mm or positive interferon gamma release assay (IGRA) or history of close contact with active pulmonary TB\* within 3 months prior entry visit or residing in a high TB burden area\*\* NOTE \* close contact is referred to person living/sharing in the same room with active pulmonary TB participants for \> 4 hours/day
• \*\* high TB burden areas are defined as areas with an estimated or reported TB prevalence of 100 to 300/100,000, according to the WHO. Thailand is included in high TB burden areas.
• Laboratory values obtained within 30 days prior to entry
• Absolute neutrophil count (ANC) \>750 cells/mm3
• Hemoglobin \>7.4 g/dL
• Platelet count \>50,000/mm3
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) \<3x upper limit of normal (ULN)
• Total bilirubin \<2.5 X ULN
• Chest radiograph or chest computed tomography (CT) scan without evidence of active tuberculosis, unless one has been performed within 90 days prior to entry.
• Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable non-hormonal form of contraceptive (i.e., condoms, IUD, diaphragm) during RPT treatment and contraception should be remain to 6 weeks post RPT NOTE Female participants who are not of reproductive potential or whose male partner(s) have undergone successful vasectomy with documented azoospermia or have documented azoospermia are eligible without requiring the use of contraceptives. Participant-reported history is acceptable documentation of menopause, hysterectomy, or bilateral oophorectomy or bilateral tubal ligation.
• All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization) while receiving RPT and for 6 weeks after stopping this drug.
• Body weight \> 40 kg
• Ability and willingness of participant to provide informed consent

You may not qualify if:

• Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior to study entry or presence of any confirmed or probable active TB at screening.
• History of Isoniazid (INH) or Rifampicin (RIF)/Rifabutin (RFB) resistant TB at any time prior to study entry or known exposure to INH or RIF/RFB resistant TB (e.g., household member of a person with MDR or XDR TB) at any time prior to study entry.
• Treatment for \>14 consecutive days with a rifamycin or \>30 consecutive days with INH at any time during the 2 years prior to enrollment.
• Current or planned use of protease inhibitor-based ART.
• Currently on a salvage ART regimen, defined as a regimen started due to confirmed HIV virologic failure on a prior ART regimen or due to known HIV drug resistance.
• History of liver cirrhosis at any time prior to study entry.
• Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to entry.
• Diagnosis of porphyria at any time prior to study entry.
• Peripheral neuropathy ≥Grade 2 according to the Division of AIDS (DAIDS) Toxicity Table, within 90 days prior to study entry.
• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
• Pregnancy or breastfeeding

Sponsors & Collaborators

• The HIV Netherlands Australia Thailand Research Collaboration: lead
• King Chulalongkorn Memorial Hospital: collaborator
• Police General Hospital: collaborator
• Pranangklao Hospital: collaborator
• Taksin Hospital: collaborator
• Bhumibol Adulyadej Hospital: collaborator
• Klang Hospital: collaborator
• Chiang Rai Prachanukroh Hospital: collaborator
• Sanpatong Hospital: collaborator
• Queen Sawang Vadhana Memorial Hospital: collaborator
• Buddhachinnaraj Hospital: collaborator
• Maharat Nakhon Ratchasima Hospital: collaborator
• HatYai Hospital: collaborator
• Srinagarind Hospital, Khon Kaen University: collaborator
• Sisaket Hospital: collaborator
• The Public Health Centre 28 Krung thon buri: collaborator

Study Sites (16)

Klang Hospital

Bangkok, 10100, Thailand

Location

Bhumibol Adulyadej Hospital

Bangkok, 10220, Thailand

Location

HIV-NAT, Thai Red Cross AIDS Research Centre

Bangkok, 10330, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Police General Hospital

Bangkok, 10330, Thailand

Location

Taksin Hospital

Bangkok, 10600, Thailand

Location

the Public Health Centre 28 Krung thon buri

Bangkok, 10600, Thailand

Location

Sanpatong Hospital

Chiang Mai, 50120, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiang Rai, 57000, Thailand

Location

Queen Savang Vadhana Memorial Hospital

Chon Buri, 20110, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Maharat Nakhon Ratchasima Hospital

Nakhon Ratchasima, 30000, Thailand

Location

Pranangklao Hospital

Nonthaburi, 11000, Thailand

Location

Buddhachinnaraj Hospital

Phitsanulok, 65000, Thailand

Location

Sisaket Hospital

Si Sa Ket, 33000, Thailand

Location

Hatyai Hospital

Songkhla, 90110, Thailand

Location

MeSH Terms

Interventions

Isoniazid; Pyridoxine; Vitamin B 6

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Picolines

Study Officials

• Anchalee Avihingsanon, MD, PhD

  HIV-NAT, Thai Red Cross - AIDS Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 24, 2018
• Study Start: August 15, 2019
• Primary Completion (Estimated): March 1, 2038
• Study Completion (Estimated): March 1, 2038
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TH (16)