Window Prophylaxis for Pediatric Tuberculosis Prevention Trial

Not Applicable

Not yet recruiting

• Conditions: Tuberculosis Infection; Household Contacts; Children; Adolescent; Tuberculosis Infection, Latent; Tuberculosis
• Interventions: Drug: Standard of care tuberculosis prophylaxis with weekly rifapentine and isoniazid for 12 weeks; Drug: Tuberculosis window prophylaxis with weekly rifapentine and isoniazid for 12 weeks

• Registration Number: NCT07086820
• Lead Sponsor: Pontificia Universidad Catolica de Chile

Brief Summary

The goal of this cluster-randomized controlled trial is to evaluate the effectiveness of tuberculosis preventive treatment (TPT) administered during the "window period" to prevent new Mycobacterium tuberculosis infections in children and adolescents.

The main question it aims to answer is:

Can immediate TPT reduce the incidence of IGRA conversions in children and adolescents who are household contacts of a newly diagnosed pulmonary tuberculosis patient?

Researchers will compare the incidence of new tuberculosis infections-measured by IGRA conversion at 12 weeks-between participants who receive immediate TPT while still uninfected (baseline IGRA-negative) and those who receive standard care, in which TPT is not offered to IGRA-negative contacts.

Participants will be:

1. Tested for M. tuberculosis infection using the Interferon-Gamma Release Assay (IGRA), specifically the QuantiFERON-TB Gold Plus, at enrollment and after 12 weeks of follow-up.

2. Take weekly isoniazid and rifapentine for 12 weeks if:

1. They are assigned to the intervention arm (regardless of baseline IGRA result), or

2. They are in the control arm and test IGRA-positive at baseline.

Additionally, participants from the control arm who experience an IGRA conversion at 12 weeks (following the primary outcome assessment) will also receive TPT, as per standard of care.

Detailed Description

Mycobacterium tuberculosis acquisition following exposure is a common occurrence, but it remains challenging to diagnose, often requiring serial testing, as immunological responses (e.g., tuberculin skin test or interferon-gamma release assays) can take weeks to provide evidence of infection. Although tuberculosis infection is generally asymptomatic, research has shown that active mycobacterial replication and inflammation occur, and its long-term effects are not well understood due to the complexity of host-pathogen interactions and delayed disease progression. While antituberculosis prophylaxis has traditionally aimed at preventing the progression from established tuberculosis infection to active tuberculosis disease, recent studies suggest that prophylaxis administered during the "window period" after exposure may also prevent its acquisition, particularly in very young children.

This trial will help determine the effectiveness of tuberculosis prophylaxis administered during the window period in preventing the acquisition of tuberculosis infection in children and adolescents exposed in household settings. If successful, the findings may inform broader strategies for tuberculosis prevention, particularly in reducing reservoirs of Mycobacterium tuberculosis and contributing to the global tuberculosis elimination efforts.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-17
• Study First Submitted QC: 2025-07-17
• Last Update Submitted: 2025-07-17
• Study First Posted: 2025-07-25
• Last Update Posted: 2025-07-25
• Study Start: 2025-10-01
• Primary Completion: 2028-05
• Study Completion: 2028-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 647

Inclusion Criteria

• Household contacts of patient (index case) with a new diagnosis of microbiologically confirmed pulmonary tuberculosis
• Age ≥5 to <18 years old

Exclusion Criteria

• Suspected active tuberculosis in initial assessment (clinical or radiological)
• Current pregnancy or breastfeeding
• Immunocompromised
• Allergy or contraindication to isoniazid or rifapentine
• Chronic liver disease or alcohol use disorder
• History of previous treatment for active or latent tuberculosis infection
• Previous tuberculin skin test
• Household contacts of a tuberculosis index patient with a known or suspected drug-resistant M. tuberculosis strain
• Household contacts or a tuberculosis index patient currently living away from home for more than four weeks
• Household contacts of a tuberculosis index patient who have already received more than 15 daily doses of antituberculous treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care tuberculosis prophylaxis	Standard of care tuberculosis prophylaxis with weekly rifapentine and isoniazid for 12 weeks	In the Control Arm, only participants with a positive baseline IGRA result will receive tuberculosis preventive treatment (TPT). Therefore, TPT will not be given to participants with a negative baseline IGRA result at enrollment.
Window tuberculosis prophylaxis	Tuberculosis window prophylaxis with weekly rifapentine and isoniazid for 12 weeks	In the Intervention Arm, all participants will be immediately prescribed tuberculosis preventive treatment (TPT), irrespective of their baseline IGRA result. Therefore, TPT will be given to participants having either positive or negative baseline IGRA results at enrollment.

Primary Outcome Measures

Name	Time	Method
Incidence of new tuberculosis infections (all IGRA conversions) from enrollment until the end of follow-up in both study arms	At the end of follow-up at 12 weeks (accepted range: ≥ 11 - ≤15 weeks)

Secondary Outcome Measures

Name	Time	Method
Incidence of new tuberculosis infections (IGRA conversions) with high IGRA thresholds (IFN-γ ≥1.0 IU/mL) at the end of follow-up in both study arms	At the end of follow-up at 12 weeks (accepted range ≥11 - ≤15 weeks)
Incidence of active tuberculosis development until the end of follow-up in both study arms	From 4 weeks after enrollment to the end of follow-up at 12 weeks (accepted range ≥ 4 - ≤15 weeks)
Prevalence of tuberculosis infections (all IGRA positive) at the end of follow-up in both study arms.	At the end of follow-up at 12 weeks (accepted range ≥ 11 - ≤15 weeks)
Incidence of 3HP-related adverse events at 12 weeks in both study arms	From TPT initiation to completion or last dose received, in both study arms (accepted range ≥ 1 day - ≤15 weeks)

Trial Locations

Locations (13)

Hospital Dr. Carlos Cisterna; 🇨🇱 Calama, Antofagasta, Chile

Hospital de Niños Roberto del Río; 🇨🇱 Independencia, Santiago, Chile

Complejo Asistencial Dr. Sótero Del Río; 🇨🇱 Puente Alto, Santiago, Chile

Hospital El Pino; 🇨🇱 San Bernardo, Santiago, Chile

Hospital Alto Hospicio; 🇨🇱 Alto Hospicio, Tarapacá, Chile

Hospital Claudio Vicuña; 🇨🇱 San Antonio, Valparaíso, Chile

Hospital Dr. Gustavo Fricke; 🇨🇱 Viña Del Mar, Valparaíso, Chile

Hospital de Coquimbo; 🇨🇱 Coquimbo, Chile

Hospital Clínico Félix Bulnes; 🇨🇱 Santiago, Chile

Hospital Clínico San Borja Arriarán; 🇨🇱 Santiago, Chile

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