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

Tuberculous Uveitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05005637
• Other study ID #: 06/DIPI/2021
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: July 27, 2021
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: Fakultas Kedokteran Universitas Indonesia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: June 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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).

2. Age >18 years old

3. Lives in Jakarta/Bogor/Depok/Tangerang/Bekasi area or willing to participate in research until the end of monitoring program

4. Willing to participate in the research and sign the informed consent after receiving explanation regarding the research

Exclusion Criteria:

1. Patients with positive aqueous tap examination results on one of the examination panels for the bacteria causing infectious uveitis according to the standard examination

2. Anterior uveitis patient with a positive HLA-B27 test result

3. The patient is proven to have active TB or lives in the same house with an active TB patient

4. Patients are included in the TB reactivation risk index group according to the 2018 WHO LTBI (Latent Tuberculosis Incident) Guideline

5. HIV positive patient

6. Patients with uveitis sanata at the first visit

7. Patients with visual acuity less than 1/300 or showing signs of preptisis based on ophthalmological examination and ultrasound of the eye

8. The patient has a history of previous ATT consumption

9. Patients with impaired liver function or other systemic conditions which according to the Internal Medicine Department are not eligible to receive ATT

10. The patient has a history of taking antibiotics in the last 1-2 weeks

11. The patient is not willing to sign the informed consent

12. The patient was pregnant at the first visit or was planning to become pregnant during the study period

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculous Uveitis
• Uveitis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Indonesia	Cipto Mangunkusumo National Central General Hospital	Jakarta Pusat	DKI Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Fakultas Kedokteran Universitas Indonesia

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Treatment Failure	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.	6 months after the initial therapy