The Effectivity of Anti Tuberculosis Therapy in Idiopathic Uveitis With Positive IGRA

Sponsor

Fakultas Kedokteran Universitas Indonesia (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05005637

Collaborator

(none)

Enrollment

Location

Arms

34.2

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The reported incidence of uveitis is 52 persons per year per 100,000 population, with a greater incidence estimated in developing countries, including Indonesia. Uveitis has challenges in diagnosis and therapy, due to the existence of an immunological privilege mechanism, so it is not easy to obtain diagnostic markers or provide appropriate therapy. In uveitis, a work-up examination looking for signs in the entire body or systemic disease is often conducted.

Up until today, establishing the diagnosis of tuberculosis (TB)-associated uveitis is still a challenge. From histopathological studies, TB germs are difficult to find. Wreblowski et al. found that paucibacillary conditions also made TB bacteria difficult to find by PCR and tuberculin test results were also not completely reliable. The development of IGRA (Interferon-Gamma Release Assay) assays, such as QuantiFERON-Gold TB (QFT) has been investigated. Our previous study found that IGRA-positive uveitis patients with type 1 IFN gene expression score >5.61 were more likely to have active TB uveitis. In addition, serum C1q examination also showed an inverse correlation with this score.

Regarding therapy, until now corticosteroids and cycloplegics are the mainstay treatment for uveitis. However, appropriate administration of anti-infective drugs is necessary in cases of infection. Inflammation in TB-associated uveitis is thought to be the result of the immune response that occurs as a result of paucibacillary TB infection. Examinations can be redundant and problematic. Determination of therapy is also a dilemma because it is difficult to determine the right patient candidate for administration of anti-tuberculosis therapy (ATT). The protocol of ATT administration itself has not been standardized so it often follows the extra pulmonary TB protocol and there has been no reliable clinical trial research on ATT administration in patients with suspected TB uveitis yet no TB microorganisms are found directly in the eyes or other organs.

On this basis, the investigators planned a prospective randomized clinical trial study that involve idiopathic uveitis patients with positive IGRA test, to assess the effectivity of ATT compared to oral steroids. In addition, this study can also be used as a basis for validation of type 1 IFN scores and serum C1q as diagnostic/prognostic biomarkers in cases of TB-associated uveitis.

Condition or Disease	Intervention/Treatment	Phase
Tuberculous Uveitis	Drug: Anti Tuberculosis Drug Drug: Prednisone tablet	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effectivity of Anti Tuberculosis Therapy in Idiopathic Uveitis With Positive Interferon Gamma Release Assay (IGRA): A Randomized Clinical Trial

Actual Study Start Date :

Jul 27, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti Tuberculosis Therapy Dosage form: ATT fixed-dose combination (FDC). FDC intensive phase containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), while FDC continuation phase containing rifampicin-isoniazid. Dosage: according to body weight, 30-37 kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets, more than 70 kg: 5 tablets. Frequency: Intensive phase: once daily. Continuation phase: 3 times/week. Duration: 6 months (2 months of FDC intensive phase + 4 months of FDC continuation phase)	Drug: Anti Tuberculosis Drug ATT will be given in the form of fixed drug combination (FDC). Each patient will get a regimen of 2RHZE (2 months of FDC intensive phase, which contains of Rifampicin, Isoniazide, Pirazinamide, Ethambutol) + 4RH (4 months of FDC continuation phase, which contains of Rifampicin and Isoniazid). The dosage will be according to body weight, 30-37 kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets, more than 70 kg: 5 tablets. FDC drugs have to be consumed daily during intensive phase and three times a week during continuation phase.
Active Comparator: Oral Steroid Dosage form: Oral prednisone Dosage: 1 mg/kgBW/day (max 60 mg/day) Duration: until the uveitis is controlled or up to 4 weeks of administration, after that the dose will be tappered off gradually.	Drug: Prednisone tablet Oral prednisone will be given at the dose of 1 mg/kgBW/day (max 60 mg/day) until the uveitis is controlled or up to 4 weeks of administration, after that the dose will be tappered off gradually.

Arm

Intervention/Treatment

Experimental: Anti Tuberculosis Therapy

Dosage form: ATT fixed-dose combination (FDC). FDC intensive phase containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), while FDC continuation phase containing rifampicin-isoniazid. Dosage: according to body weight, 30-37 kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets, more than 70 kg: 5 tablets. Frequency: Intensive phase: once daily. Continuation phase: 3 times/week. Duration: 6 months (2 months of FDC intensive phase + 4 months of FDC continuation phase)

Drug: Anti Tuberculosis Drug

ATT will be given in the form of fixed drug combination (FDC). Each patient will get a regimen of 2RHZE (2 months of FDC intensive phase, which contains of Rifampicin, Isoniazide, Pirazinamide, Ethambutol) + 4RH (4 months of FDC continuation phase, which contains of Rifampicin and Isoniazid). The dosage will be according to body weight, 30-37 kg: 2 tablets, 38-54 kg: 3 tablets, 55-70 kg: 4 tablets, more than 70 kg: 5 tablets. FDC drugs have to be consumed daily during intensive phase and three times a week during continuation phase.

Active Comparator: Oral Steroid

Dosage form: Oral prednisone Dosage: 1 mg/kgBW/day (max 60 mg/day) Duration: until the uveitis is controlled or up to 4 weeks of administration, after that the dose will be tappered off gradually.

Drug: Prednisone tablet

Oral prednisone will be given at the dose of 1 mg/kgBW/day (max 60 mg/day) until the uveitis is controlled or up to 4 weeks of administration, after that the dose will be tappered off gradually.

Outcome Measures

Primary Outcome Measures

Percentage of Treatment Failure [6 months after the initial therapy]
Treatment will be categorized as a failure if subject did not meet the following criteria at the 6-month follow-up post initial therapy, (1) less than or equal to 0.5+ anterior chamber cells by SUN criteria, less than or equal to 0.5+ vitreous haze clinical grading using the NEI scale, and no active retinal or choroidal lesions; and (2) no more than 7.5 mg of oral prednisone daily and less than or equal to 2 drops of prednisolone acetate 1% (or equivalent) per day; or in other words, the subject has persistent inflammation that keeps getting worse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient that is newly diagnosed with uveitis of unknown origin/idiopathic (as evidenced by a series of uveitis work-up tests) and tested positive for IGRA (>0.35 U/ml).
Age >18 years old
Lives in Jakarta/Bogor/Depok/Tangerang/Bekasi area or willing to participate in research until the end of monitoring program
Willing to participate in the research and sign the informed consent after receiving explanation regarding the research

Exclusion Criteria:

Patients with positive aqueous tap examination results on one of the examination panels for the bacteria causing infectious uveitis according to the standard examination
Anterior uveitis patient with a positive HLA-B27 test result
The patient is proven to have active TB or lives in the same house with an active TB patient
Patients are included in the TB reactivation risk index group according to the 2018 WHO LTBI (Latent Tuberculosis Incident) Guideline
HIV positive patient
Patients with uveitis sanata at the first visit
Patients with visual acuity less than 1/300 or showing signs of preptisis based on ophthalmological examination and ultrasound of the eye
The patient has a history of previous ATT consumption
Patients with impaired liver function or other systemic conditions which according to the Internal Medicine Department are not eligible to receive ATT
The patient has a history of taking antibiotics in the last 1-2 weeks
The patient is not willing to sign the informed consent
The patient was pregnant at the first visit or was planning to become pregnant during the study period