Clinical trial NCT05005637: The Effectivity of Anti Tuberculosis Therapy in Idiopathic Uveitis with Positive IGRA
Official title: Antitubercular Treatment for Uveitis of Undetermined Cause with Positive QuantiFERON-TB Gold Plus: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculous Uveitis
Keywords: Tuberculosis
Uveitis
Tuberculous Uveitis
Idiopathic Uveitis
Interferon Gamma Release Assay
Anti Tuberculosis Therapy
IGRA
ATT
Quantiferon-TB GoldPlus
Lead sponsor: Fakultas Kedokteran Universitas Indonesia
Sponsor class: OTHER
First posted: 2021-08-13
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Treatment Failure
timeFrame: 6 months after the initial therapy
measure: Response to Treatment
timeFrame: 6 months after initial treatment
Secondary outcomes:
measure: Time to Uveitis Resolution
timeFrame: 90 days after the visit of first uveitis resolution was recorded
measure: Uveitis Relapse
timeFrame: 6 months after the initial therapy
measure: Eye-Level outcome (Visual Acuity)
timeFrame: 6 months after baseline visit
measure: Eye-Level outcome (Secondary glaucoma)
timeFrame: 6 months after baseline visit
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Cipto Mangunkusumo National Central General Hospital
state: DKI Jakarta
Study officials:
affiliation: Fakultas Kedokteran Universitas Indonesia
name: Rina La Distia Nora, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Putera I, Ten Berge JCEM, Thiadens AAHJ, Dik WA, Agrawal R, van Hagen PM, La Distia Nora R, Rombach SM. Relapse in ocular tuberculosis: relapse rate, risk factors and clinical management in a non-endemic country. Br J Ophthalmol. 2024 Nov 22;108(12):1642-1651. doi: 10.1136/bjo-2024-325207.
citation: Putera I, Ten Berge JCEM, Thiadens AAHJ, Dik WA, Agrawal R, van Hagen PM, La Distia Nora R, Rombach SM. Clinical Features and Predictors of Treatment Outcome in Patients with Ocular Tuberculosis from the Netherlands and Indonesia: The OculaR TB in Low versus High Endemic Countries (ORTEC) Study. Ocul Immunol Inflamm. 2025 Jan;33(1):86-97. doi: 10.1080/09273948.2024.2359614. Epub 2024 May 31.
citation: Putera I, Schrijver B, Ten Berge JCEM, Gupta V, La Distia Nora R, Agrawal R, van Hagen PM, Rombach SM, Dik WA. The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies. Prog Retin Eye Res. 2023 Jul;95:101189. doi: 10.1016/j.preteyeres.2023.101189. Epub 2023 May 25.
citation: Ludi Z, Sule AA, Samy RP, Putera I, Schrijver B, Hutchinson PE, Gunaratne J, Verma I, Singhal A, Nora RD, van Hagen PM, Dik WA, Gupta V, Agrawal R. Diagnosis and biomarkers for ocular tuberculosis: From the present into the future. Theranostics. 2023 Apr 1;13(7):2088-2113. doi: 10.7150/thno.81488. eCollection 2023.
citation: La Distia Nora R, Sitompul R, Bakker M, Susiyanti M, Edwar L, Sjamsoe S, Singh G, van Hagen MP, Rothova A. Tuberculosis and other causes of uveitis in Indonesia. Eye (Lond). 2018 Mar;32(3):546-554. doi: 10.1038/eye.2017.231. Epub 2017 Nov 3.
citation: Betzler BK, Putera I, Testi I, La Distia Nora R, Kempen J, Kon OM, Pavesio C, Gupta V, Agrawal R. Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis. Surv Ophthalmol. 2023 Mar-Apr;68(2):241-256. doi: 10.1016/j.survophthal.2022.10.001. Epub 2022 Oct 19.