Clinical trial NCT06191692: 1HP Versus 3HR in the Treatment of Tuberculosis Infection in Vietnam
Official title: An Open-label, Randomized Controlled Trial of the New One-month Regimen Versus the Current Three-month Regimen for the Treatment of Tuberculosis Infection in Vietnam
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Tuberculosis Infection
Keywords: Tuberculosis
TB preventive therapy
Tuberculosis infection
Latent TB infection
LTBI
TBI
Lead sponsor: Freundeskreis Für Internationale Tuberkulosehilfe e.V
Sponsor class: OTHER
First posted: 2024-01-05
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Households will be randomized in a 1:1 ratio to the two treatment groups (1HP/3HR) using cluster randomization
Primary purpose: TREATMENT

Brief summary: Introduction: Tuberculosis (TB) infection is a key driver of the TB pandemic, with over 10.6 million people fell ill with TB disease in 2022. About one-quarter of the global population is estimated to be infected with TB bacteria. Around 5-10% of people with TB infection will develop active and contagious TB disease, which could be largely avoided if TB infection is identified and given effective preventative treatment, before progression to active disease. The long treatment of TB infection with regimens lasting from three to nine months is a significant barrier to treatment completion in individuals with a confirmed diagnosis of TB infection. Adapting a shorter regimen than the current regimens could lead to a higher treatment completion rate and increased uptake of preventative therapy for TB, as well as reduced side effects.

Methods and analysis: An open-label, randomized clinical trial (1:1) will be performed in two study sites in Ha Noi, Vietnam (Vietnam National Lung Hospital and Ha Noi Lung Hospital). Adult household contacts (n=350) of people with new, bacteriologically-confirmed, pulmonary, drug-susceptible TB who initiate treatment will be invited to participate.

Aim: To compare the TB preventive therapy completion rates and adverse event incidence between a new one-month regimen (1HP) versus the current three-month regimen (3HR)\*.

\*1HP= one month of daily isoniazid (H/INH) and rifapentine (P/RPT) 3HR= three months of daily isoniazid (H/INH) and rifampicin (R/RIF)

Detailed description: Latent TB infection, hereafter referred to as TB infection, is a key driver of the TB pandemic. Over 10.6 million people developed active TB in 2022 and about one-quarter of the global population is estimated to be infected with TB bacteria, meaning approximately two billion people are affected worldwide. On average, 5-10% of people with TB infection will develop active TB, usually within the first five years after their initial TB infection. Therefore, preventative treatment is a fundamental component of a comprehensive strategy to end TB.

The current duration of TB Prevention Treatment (TPT), which lasts from three to nine months, is a significant barrier resulting in the low uptake of the TPT.

A one-month TPT regimen using two drugs (isoniazid and rifapentine, 1HP) was proven effective and had higher completion rates for people living with HIV; however, the initial demonstration trial was not performed in a cohort of people without HIV. The use of a shorter TPT regimen than the current three-month TPT regimen could lead to higher completion rates and increased uptake among a large number of individuals in need of TPT. Moreover, it may potentially reduce adverse events as well as decrease the medical and non-medical costs associated with the TPT.

Therefore, the investigators propose a comprehensive study of shortened TPT for TB infection in Vietnam, a low HIV burden setting.

An open-label, randomized controlled trial (TBIshort) of the new one-month TPT regimen versus the current three-month regimen for the treatment of TB infection in Vietnam will be performed and funded by Stop TB Partnership's TB REACH initiative to compare treatment completion rate and safety between the two regimens. Households will be randomized in a 1:1 ratio to the two arms using cluster randomization. All participants from the same household will be allocated to the same treatment regimen arm. The proposed study will address key knowledge gaps, and provide objective evidence to guide decision-making for the use of the 1HP regimen for the treatment of TB infection in a low HIV burden setting.

Aims

1. Main objective:

   Objective 1: Compare the treatment adherence and safety of the 1HP regimen and the standard 3HR regimen for TB infection treatment
2. Specific objectives:

Objective 2: Compare the treatment completion rates for TB infection between 1HP and 3HR regimens.

Objective 3: Compare adverse events incidence for 1HP and 3HR regimens during three months from treatment start.

Eligibility criteria: Inclusion Criteria:

* Household contacts of people with new, bacteriologically-confirmed, pulmonary, drug-susceptible TB who initiated treatment with residence in the intervention areas;
* Positive QFT-Plus or TST results (TST induration of at least 5mm)
* Agree to remain in contact and provide updated information as necessary, and have no current plans to relocate outside the designed area for the duration of the study;
* Age ≥ 18 years;
* Capable of providing signed informed consent;
* Willing to participate in the study visits and procedures

Exclusion Criteria:

* Indeterminate results on QFT-Plus;
* Clinical or radiographic suspicions or history of previous active TB;
* Known hypersensitivity or contraindication to any components of the regimens;
* Weight \&amp;lt;30kg;
* Acute or chronic liver failure with elevated liver enzymes or evidence of liver dysfunction such as jaundice or a history of liver failure caused by isoniazid or rifampicin; History of liver cirrhosis at any time before study entry;
* Infection with suspected or confirmed tuberculosis strains resistant to isoniazid or rifampicin;
* Porphyria- Porphyrin metabolism disorder;
* Polyneuropathy (self-reported/ confirmed);
* Pregnant or planning to become pregnant within 120 days of enrollment;
* Any other severe underlying condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial;
* Participation in other clinical intervention trials or research protocols (participation in other studies that do not involve an intervention may be allowed, but this must be discussed and approved by the Chief Investigator).

Primary outcomes:
measure: 1. % Adequate adherence in each arm
timeFrame: From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B), to be reported at the end of the trial.
Secondary outcomes:
measure: The incidence rate of severe adverse events among two arms.
timeFrame: From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)
measure: Comparison of adherence measured as the proportion of treatment taken in the regimens (1HP vs 3HR).
timeFrame: From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)
measure: The incidence rate of a targeted event of grade 3,4 or 5*** and one grade increase from the baseline among two arms.
timeFrame: From study entry at Week 0 through up to 16 weeks of 3HR (Arm A), or up to 6 weeks of 1HP (Arm B)
Other outcomes:
Locations:
city: Hà Nội
country: Vietnam
facility: Vietnam National Lung Hospital
state: Ha Noi
city: Hà Nội
country: Vietnam
facility: Ha Noi Lung Hospital
Study officials:
References: