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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03785106

Recruitment Status : Recruiting

First Posted : December 24, 2018

Last Update Posted : September 9, 2020

See Contacts and Locations

Sponsor:

Collaborators:

King Chulalongkorn Memorial Hospital

Police General Hospital

Pranangklao Hospital

Taksin Hospital

Bhumibol Adulyadej Hospital

Klang Hospital

Chiang Rai Prachanukroh Hospital

Sanpatong Hospital

Queen Sawang Vadhana Memorial Hospital

Buddhachinnaraj Hospital

Maharat Nakhon Ratchasima Hospital

Hatyai Hospital

Srinagarind Hospital, Khon Kaen University

Sisaket Hospital

The Public Health Centre 28 Krung thon buri

Information provided by (Responsible Party):

The HIV Netherlands Australia Thailand Research Collaboration

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV-infected Participants With Latent TB Infection in High TB Burden Country	Drug: Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) Drug: Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)	Phase 3

Detailed Description:

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. The primary objective will be efficacy of active TB prevention. The study will also assess safety and tolerability of the regimens, adherence to the treatments, and patterns of antibiotic resistance among Mycobacterium tuberculosis (MTB) isolates in participants who fail on these prophylactic regimens.

Under this study, there is one substudy entitled, "Pharmacokinetic study of rifapentine, dolutegravir, and tenofovir alafenamide in HIV-infected individual with latent tubersulosis infection". There will be a subgroup of patients who will participate in this pharmacokinetic study of rifapentine and dolutegravir (DTG) / tenofovir alafenamide (TAF). Randomization is based on cluster of differentiation 4 (CD4) categories : < 200, 200-350, > 500 cells/mm3 and VL <50 or >50 copies/ml.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	2500 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	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.
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Implementation for Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals Using Novel Regimen of Isoniazid/Rifapentine Daily (4 Weeks) Compared to Isoniazid/Rifapentine Weekly (12 Weeks)
Actual Study Start Date :	August 15, 2019
Estimated Primary Completion Date :	March 2023
Estimated Study Completion Date :	March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Tuberculosis

Drug Information available for: Isoniazid Pyridoxine hydrochloride Pyridoxine Vitamin B Complex Rifapentine

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1HP 4-week daily regimen of weight-based RPT and INH, plus pyridoxine (vitamin B6)	Drug: Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)
Active Comparator: 3HP 12-weekly INH/RPT regimen, plus pyridoxine (vitamin B6)	Drug: Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)

Outcome Measures

Primary Outcome Measures :

efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study) [ Time Frame: 3 years ]
proportion of participants that do not have active TB by the end of the study
safety of the regimens (proportion of participants that do not have any side effects throughout the study period) [ Time Frame: 3 years ]
proportion of participants that do not have any side effects throughout the study period
tolerability to the regimens (proportion of participants that can complete the treatment course) [ Time Frame: 3 years ]
proportion of participants that can complete the treatment course
prevalence of drug resistance of MTB [ Time Frame: 3 years ]
proportion of participants with drug resistance to MTB

Secondary Outcome Measures :

severity of the condition [ Time Frame: 3 years ]
proportion of participants that have side effects of grade more than or equal to 3 signs
presence of symptoms [ Time Frame: 3 years ]
proportion of participants that have symptoms during the study period
level of CBC [ Time Frame: 3 years ]
assess the level of CBC
level of ALT [ Time Frame: 3 years ]
assess the level of ALT
level of AST [ Time Frame: 3 years ]
assess the level of AST
level of total bilirubin [ Time Frame: 3 years ]
assess the level of total bilirubin
level of ALK [ Time Frame: 3 years ]
assess the level of ALK
level of creatinine [ Time Frame: 3 years ]
assess the level of creatinine
death [ Time Frame: 3 years ]
time from randomization to death from any cause (TB and non TB events)
when TB culture becomes positive [ Time Frame: 3 years ]
how much time does it take to have positive TB culture
when TB is confirmed by clinical examination [ Time Frame: 3 years ]
how much time does it take to have TB diagnosed via clinical examination
adherence to LTBI treatment [ Time Frame: 3 years ]
proportion of pills missed during treatment period based on self report
consistency of taking LTBI treatment [ Time Frame: 3 years ]
proportion of pills missed during treatment period based on clinical assessment
treatment discontinuation [ Time Frame: 3 years ]
proportion of participants with permanent LTBI treatment discontinuation due to all causes
discontinuation of study due to adverse drug reactions [ Time Frame: 3 years ]
Proportion of participants that have discontinued the study because of adverse drug reactions
CD4 count [ Time Frame: 3 years ]
CD4 count at baseline
CD4 count to confirmed or probable TB [ Time Frame: 3 years ]
CD4 count at time from randomization to culture-confirmed or probable TB
time it takes for TB to be confirmed by IGRA [ Time Frame: 3 years ]
how much time does it take to confirm TB diagnosis via IGRA
TST result at baseline [ Time Frame: day 0 ]
TST result at day 0

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
18 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

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03785106

Contacts

Layout table for location contacts

Contact: Anchalee Avihingsanon, MD, PhD	026523040	anchaleea2009@gmail.com
Contact: June Ohata, BS	026523040	juneohata4@gmail.com

Locations

Layout table for location information

Thailand
Klang Hospital	Not yet recruiting
Bangkok, Thailand, 10100
Contact: Praniti Danpornprasert, MD 66897702021 praniti_d@hotmail.com
Principal Investigator: Praniti Danpornprasert, MD
Bhumibol Adulyadej Hospital	Not yet recruiting
Bangkok, Thailand, 10220
Contact: Chris Fujitnirun, MD 66834477602 chris_nirun@hotmail.com
Principal Investigator: Chris Fujitnirun, MD
HIV-NAT, Thai Red Cross AIDS Research Centre	Recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon, MD, PhD 662 6523040 anchaleea2009@gmail.com
Contact: June Ohata, BS 026523040 ext 147 juneohata4@gmail.com
King Chulalongkorn Memorial Hospital	Not yet recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon, MD, PhD 66868128889 anchaleea2009@gmail.com
Principal Investigator: Anchalee Avihingsanon, MD, PhD
Police General Hospital	Not yet recruiting
Bangkok, Thailand, 10330
Contact: Jirayu Visuthranukul, MD 6622076000 nutjv@yahoo.com
Principal Investigator: Jirayu Visuthranukul, MD
Taksin Hospital	Not yet recruiting
Bangkok, Thailand, 10600
Contact: Supunnee Jirajariyavej, MD 66813744264 jsupunee@yahoo.com
Principal Investigator: Supunnee Jirajariyavej, MD
the Public Health Centre 28 Krung thon buri	Not yet recruiting
Bangkok, Thailand, 10600
Contact: Thitisant Palakawong, MD 6628608210 thitisant@gmail.com
Principal Investigator: Thitisant Palakawong, MD
Sanpatong Hospital	Not yet recruiting
Chiang Mai, Thailand, 50120
Contact: Virat Klinbuayaem, MD 6653311404 kggvirat@hotmail.com
Principal Investigator: Virat Klinbuayaem, MD
Chiangrai Prachanukroh Hospital	Not yet recruiting
Chiang Rai, Thailand, 57000
Contact: Worarat Imsanguan, MD 66815568918 minkworat@gmail.com
Principal Investigator: Worarat Imsanguan, MD
Queen Savang Vadhana Memorial Hospital	Not yet recruiting
Chon Buri, Thailand, 20110
Contact: Palakorn Panarat, MD 66824401199 panarat_3rd@hotmail.com
Principal Investigator: Palakorn Panarat, MD
Srinagarind Hospital	Not yet recruiting
Khon Kaen, Thailand, 40002
Contact: MD 66815925907 ploencha@kku.ac.th
Principal Investigator: Ploenchan Chetchotisakd, MD
Maharat Nakhon Ratchasima Hospital	Not yet recruiting
Nakhon Ratchasima, Thailand, 30000
Contact: Sirichai Wiwatrojanagul, MD 66825321321 md.sirichai@gmail.com
Principal Investigator: Sirichai Wiwatrojanagul, MD
Pranangklao Hospital	Not yet recruiting
Nonthaburi, Thailand, 11000
Contact: Sripetcharat Mekviwattanawong, MD 66818705700 sripetcharat@gmail.com
Principal Investigator: Sripetcharat Mekviwattanawong, MD
Buddhachinnaraj Hospital	Not yet recruiting
Phitsanulok, Thailand, 65000
Contact: Porntip Treebupachatsakul, MD 66915349221 pornpitt@gmail.com
Principal Investigator: Porntip Treebupachatsakul, MD
Sisaket Hospital	Not yet recruiting
Sisaket, Thailand, 33000
Contact: Natcha Saetiew, MD 66815937739 snatcha39@gmail.com
Principal Investigator: Natcha Saetiew, MD
Hatyai Hospital	Not yet recruiting
Songkhla, Thailand, 90110
Contact: Preudtipong Noopetch, MD 66815925907 jasommhai@hotmail.com
Principal Investigator: Preudtipong Noopetch, MD

Sponsors and Collaborators