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Status unknownNCT04117698URBAUpdated Oct 7, 2019

Multicenter, Randomized Study Evaluating the Value of Antitubercular Treatment During Recurent Anterior Uveitis (URBA)

A Phase 3 interventional study of Antitubercular treatment (RIFATER ©) and Ethambutol in Uveitis, Anterior, sponsored by Assistance Publique - Hôpitaux de Paris. Status unknown. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-07.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Oct 2019), so the status shown — last known as Not yet recruiting — may be out of date.
Phase
Phase 3
Study type
Interventional
Enrollment
116
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Uveitis accounts for 15% of the causes of legal blindness. The etiological diagnosis of uveitis is difficult because of the poor bacteriological performance of aqueous or vitreous fluid analysis. At the end of a medical and paramedical check-up, oriented by the typology of uveitis, a clinical situation is frequently encountered: idiopathic uveitis with a Quantiferon test (QFN) positive orienting to an old or recent contact with tuberculosis. Ocular tuberculosis is often characterized by a partial and transient response to corticosteroid therapy (local or general), due to predominant hypersensitivity phenomena and low inoculum. Therefore, antitubercular treatment is recommended for idiopathic posterior uveitis with positive QFN. This treatment of 6-9 months has shown, in combination with systemic corticosteroids, its effectiveness on ocular inflammation and significant decrease in recurrence frequency.

For previous uveitis with QFN positive, there is no study or recommendation in the low endemic countries on the indication of anti-tuberculosis drugs and practices are variable.

Tuberculous anterior uveitis is distinguished by high rate of relapses and chronic uveitis upon discontinuation of topic corticosteroid therapy that exposes to broad posterior synechiae leading to an ocular functional impairment. Optimizing the management of recurrent anterior uveitis is therefore crucial.

The aim of this prospective, randomized, controlled, open, two parallel arm trial is to compared antitubercular treatment "add-on "of local corticosteroid therapy to Local Corticosteroid Therapy Only in patients with recurrent or chronic anterior uveitis.

Primary outcome is the treatment succes defined as uveitis recovery at 3 months and the absence of recurrence at 18 months of follow-up.

02

Conditions studied

  • Uveitis, Anterior
03

In context

Uveitis

335 studies on the registry are indexed under Uveitis; 37 are open to participants now.

This study's planned enrollment of 116 is above the median of 30 across 208 interventional studies indexed under Uveitis.

Browse Uveitis studies →

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age≥18 years.
  2. For women of childbearing age (unless confirmed postmenopausal or sterile), βHCG negative.
  3. For subjects of childbearing age, the willingness to use adequate contraceptive measures to prevent the subject or partner of the subject from becoming pregnant during the first 6 months of the study in case of randomization in the experimental group.
  4. Recurrent anterior Uveitis (≥ 2 episodes of ocular inflammation within the past 2 years before inclusion with a free-interval of at least 3 months between ocular inflammations, patients with a second episode of ocular inflammation may be included in the study) or chronic anterior Uveitis (persistence of ocular inflammation = partial response after 3 months of well-conducted local treatment) .
  5. Positive Quantiferon test (QFN) performed after the first episode of ocular inflammation (accepted tests: Quantiferon-TB-Gold, Quantiferon-TB-Gold in tube or Quantiferon plus) with a threshold ≥ 1 IU / ml or associated with a positive ELISPOT test if the QFN level is between 0.7 and 1UI / l.

  6. Absence of other etiology that may explain anterior uveitis during etiological investigations

    1. Serology of herpes group viruses (HSV,, CMV, VZV) negative or old immunity (achieved after the first episode of ocular inflammation).
    2. TPHA, negative VDRL (performed after the 1st episode of ocular inflammation).
    3. Serologies HIV, HBV and HCV, negative (performed within the 3 months before inclusion).
    4. Negative Lyme serology (performed after the first episode of ocular inflammation) or medical history not supporting this etiology
    5. HLA B27 negative (achieved after the first episode of ocular inflammation) if recurrent or non-granulomatous uveitis
    6. Negative PCR from anterior chamber fluid for Herpes group viruses, Toxoplasma gondii and Mycobacterium tuberculosis if severe inflammation (Tyndall Cellular and / or Flare> 2+) and / or posterior synechiae .
    7. Non-contributory pulmonary imaging (performed within the last month before inclusion) (radiography or chest CT scan left to the discretion of the clinician).

    Note: The non-granulomatous character uveitis during clinical examination is not an exclusion criterion.

  7. If 4+ severity score (Tyndall and / or Flare of aqueous humor) an expert opinion is required (internist / ophthalmologist pair): with no indication to initiate an anti-tuberculosis treatment without delay.
  8. Signature of informed consent to participate in the study.
  9. Patients affiliated to the French health care insurance

Exclusion criteria

Exclusion Criteria:

  1. Weight strictly less than 50 kg
  2. Weight strictly greater than 185 kg
  3. History of cancer 5 years before inclusion (except in situ cervical cancer or non-metastatic baso or squamous cell carcinoma) or progressive malignant hemopathy.
  4. Liver failure or ALTgreater than three times the normal value or severe renal impairment (GFR \<30ml / min).
  5. Neutropenia \<1000 / mm3, Thrombocytopenia \<50,000 / mm3, Hemoglobin \<8g / dL
  6. Pulmonary or active visceral tuberculosis.
  7. Associated posterior and intermediate uveitis (indication for almost constant systemic corticosteroid therapy, and de facto contraindication to a control arm without TB treatment).
  8. Monophthalmic patient
  9. Intervention with general anesthesia during the first 6 months
  10. Clinical presentation of acute anterior uveitis type HLA B27.
  11. History of tuberculous disease treated.
  12. Systemic corticosteroid therapy or immunosuppressive therapy received within 3 months before inclusion.
  13. Local corticotherapy received for more than 15 days in the 2 months before inclusion.
  14. Hypersensitivity to the family of rifamycin, isoniazid, pyrazinamide and known ethambutol or to any of the excipients present in the medicinal products of this trial (presence, in particular, of excipients with known effect: sucrose, sodium)
  15. Known hypersensitivity to fluorometholone or any of the excipients, in particular with benzalkonium chloride.
  16. Known hypersensitivity to dexamethasone phosphate or to any of the excipients
  17. Known hypersensitivity to tropicamide, atropine or its derivatives,
  18. Known hypersensitivity to phenylephrine, thiomersal
  19. Antecedent of optic neuritis.
  20. Patients with wheat allergy (other than celiac disease).
  21. Association with praziquantel, voriconazole, which cannot be interrupted for clinical research study.
  22. Porphyries known.
  23. Patient under Valaciclovir
  24. Hyperuricemic subjects with symptomatic joint involvement

  25. Eye infections not controlled by antiinfectives, such as:

    • acute purulent bacterial infections, including Pseudomonas and Mycobacteria infections,
    • fungal infections,
    • epithelial keratitis due to Herpes simplex virus (dendritic keratitis), vaccinia virus, varicella zoster virus and most other viral infections of the cornea and conjunctiva,
    • amoebic keratitis,
  26. Perforation, ulceration and corneal injury associated with incomplete reepithelialization
  27. Known ocular hypertension caused by glucocorticoids, risk of angle closure glaucoma,
  28. Pregnancy or breastfeeding.
  29. Psychiatric disorder and / or patient under guardianship.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
116 participants (estimated)

Study arms

  • Experimental
    Antitubercular treatment and local corticosteroid therapy

    Treatment of ocular inflammation by "antitubercular treatment " add-on "of local corticosteroid therapy" comprising: * RIFATER © (Isoniazid + Rifampicin + Pyrazinamide) + Ethambutol (13.5-20 mg / kg / day) for 2 months then RIFINAH © (Isoniazid + Rifampicin) for 4 months * associated with a treatment similar to the control group.

    Drug: Antitubercular treatment (RIFATER ©) · Drug: Ethambutol · Drug: RIFINAH ©

  • No intervention
    Local Corticosteroid Therapy Only

    Treatment of Ocular Inflammation by "Local Corticosteroid Therapy Only" comprising: * Dexamethasone (DEXAFREE® eye drops) at an attack dose for one week (4 to 6 drops / d maximum and if severe inflammation 1 drop / hour) then decrease and stop over 3 weeks, with relay by fluorometholone (Flucon®) for 2 months maximum. The modalities of the decrease of the local steroids are left to the ophthalmologists own judgment. Maximum total duration of 3 months. * Mydriatic (tropicamide) 1gx3 / d if necessary. * Neosynephrine 5% if posterior synechiae. * Atropine (Alcon 0.3%) if pain.

Interventions

  • DrugAntitubercular treatment (RIFATER ©)

    Treatment of ocular inflammation by "antitubercular treatment " add-on "of local corticosteroid therapy" comprising: * RIFATER © (Isoniazid + Rifampicin + Pyrazinamide) + Ethambutol (13.5-20 mg / kg / day) for 2 months then RIFINAH © (Isoniazid + Rifampicin) for 4 months * associated with a treatment similar to the control group.

  • DrugEthambutol

    Ethambutol

  • DrugRIFINAH ©

    RIFINAH ©

06

What researchers measure

Primary outcomes

  1. Success

    Success is defined by uveitis recovery at 3 months and the absence of recurrence at 18 months of follow-up. The intensity of the ocular inflammation will be evaluated using the Standardization of Uveitis Nomenclature (SUN) classification (score of cellular Tyndall and "Flare" of the aqueous humor) Failure is therefore defined as failure to recovery at 3 months of anterior uveitis or recurrence at 18 months.

    Time frame: at 18 months

Secondary outcomes

  1. Proportion of patients having developped neutropenia

    Neutropenia will be defined as PNN less than 1000 mm3

    Time frame: at 6 months

  2. Proportion of patients having developped hepatitis with clinical signs

    Hepatitis will be defined as hepatitis with clinical signs and ALT greater than 3 times the normal value

    Time frame: at 6 months

  3. Proportion of patients having developped severe hepatitis

    Severe hepatitis will be defined will be defined as ALT greater than 5 times the normal value

    Time frame: at 6 months

  4. Proportion of patients having developped moderate or severe skin allergy

    Time frame: at 6 months

  5. Proportion of patients having developped neuritis or optic atrophy

    Time frame: at 6 months

  6. Proportion of patients having developped acute renal failure

    Time frame: at 6 months

  7. Proportion of patients having developped peripheral neuropathy

    Time frame: at 6 months

  8. Proportion of patients having developped other adverse effects

    Time frame: at 6 months

  9. Proportion of patients with recurrence

    Time frame: between 3 months and 18 months

  10. Prevalence of failure

    Time frame: at 12 months post-treatment

  11. Cumulative incidence of episodes of ocular inflammation

    Time frame: at 18 months

  12. Cumulative number of anterior uveitis episodes

    Time frame: at 18 months

  13. Tyndall score

    Time frame: at 1 month

  14. Flare's score

    Time frame: at 1 month

  15. Tyndall score

    Time frame: at 2 months

  16. Flare's score

    Time frame: at 2 months

  17. Tyndall score

    Time frame: at 3 months

  18. Flare's score

    Time frame: at 3 months

  19. Tyndall score

    Time frame: at 6 months

  20. Flare's score

    Time frame: at 6 months

  21. Tyndall score

    Time frame: at 12 months

  22. Flare's score

    Time frame: at 12 months

  23. Tyndall score

    Time frame: at 15 months

  24. Flare's score

    Time frame: at 15 months

  25. Tyndall score

    Time frame: at 18 months

  26. Flare's score

    Time frame: at 18 months

  27. Proportion of patients who developed or worsened a decrease in visual acuity

    Time frame: at 18 months

  28. Proportion of patients who developed or worsened a decrease in visual acuity

    Time frame: at 3 months

  29. Proportion of patients who developed or worsened a decrease in visual acuity

    Time frame: at 6 months

  30. Proportion of patients who developed or worsened a decrease in visual acuity

    Time frame: at 12 months

  31. Proportion of patients who developed or worsened a decrease in visual acuity

    Time frame: at 15 months

  32. Proportion of patients who developed or worsened broad posterior synechiae

    Time frame: at 3 months

  33. Proportion of patients who developed or worsened broad posterior synechiae

    Time frame: at 6 months

  34. Proportion of patients who developed or worsened broad posterior synechiae

    Time frame: at 12 months

  35. Proportion of patients who developed or worsened broad posterior synechiae

    Time frame: at 15 months

  36. Proportion of patients who developed a glaucoma

    Time frame: at 18 months

  37. Proportion of patients who developed a glaucoma

    Time frame: at 3 months

  38. Proportion of patients who developed a glaucoma

    Time frame: at 6 months

  39. Proportion of patients who developed a glaucoma

    Time frame: at 12 months

  40. Proportion of patients who developed a glaucoma

    Time frame: at 15 months

  41. Proportion of patients who developed a cataract

    Time frame: at 18 months

  42. Proportion of patients who developed a cataract

    Time frame: at 3 months

  43. Proportion of patients who developed a cataract

    Time frame: at 6 months

  44. Proportion of patients who developed a cataract

    Time frame: at 12 months

  45. Proportion of patients who developed a cataract

    Time frame: at 15 months

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 7, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04117698
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Oct 7, 2019
Start date
Nov 1, 2019 (estimated)
Primary completion
May 1, 2023 (estimated)
Completion
May 1, 2023 (estimated)
Last update
Oct 7, 2019

Study contacts

Georges Sélim TRAD
Contact
salim.trad@aphp.fr
+33149095642

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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