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

NCT04117698 | Unknown Phase 3 DMC

• 1 other identifier: P160912J
• Study Type: interventional
• Target: 116
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Uveitis, Anterior

Outcome Measures

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.

  at 18 months

Secondary Outcomes (45)

• Proportion of patients having developped neutropenia

  at 6 months

• Proportion of patients having developped hepatitis with clinical signs

  at 6 months

• Proportion of patients having developped severe hepatitis

  at 6 months

• Proportion of patients having developped moderate or severe skin allergy

  at 6 months

• Proportion of patients having developped neuritis or optic atrophy

  at 6 months

Study Arms (2)

Antitubercular treatment and local corticosteroid therapy

EXPERIMENTAL

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 ©

Local Corticosteroid Therapy Only

NO INTERVENTION

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

Antitubercular treatment (RIFATER ©) DRUG

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.

Antitubercular treatment and local corticosteroid therapy

Ethambutol DRUG

Ethambutol

Antitubercular treatment and local corticosteroid therapy

RIFINAH © DRUG

RIFINAH ©

Antitubercular treatment and local corticosteroid therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥18 years.
• For women of childbearing age (unless confirmed postmenopausal or sterile), βHCG negative.
• 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.
• 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.
• Absence of other etiology that may explain anterior uveitis during etiological investigations
• Serology of herpes group viruses (HSV,, CMV, VZV) negative or old immunity (achieved after the first episode of ocular inflammation).
• TPHA, negative VDRL (performed after the 1st episode of ocular inflammation).
• Negative Lyme serology (performed after the first episode of ocular inflammation) or medical history not supporting this etiology
• HLA B27 negative (achieved after the first episode of ocular inflammation) if recurrent or non-granulomatous uveitis
• 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 .
• 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.
• Signature of informed consent to participate in the study.
• Patients affiliated to the French health care insurance

You may not qualify if:

• Weight strictly less than 50 kg
• Weight strictly greater than 185 kg
• Liver failure or ALTgreater than three times the normal value or severe renal impairment (GFR \<30ml / min).
• Neutropenia \<1000 / mm3, Thrombocytopenia \<50,000 / mm3, Hemoglobin \<8g / dL
• Pulmonary or active visceral tuberculosis.
• Associated posterior and intermediate uveitis (indication for almost constant systemic corticosteroid therapy, and de facto contraindication to a control arm without TB treatment).
• Monophthalmic patient
• Intervention with general anesthesia during the first 6 months
• Clinical presentation of acute anterior uveitis type HLA B27.
• History of tuberculous disease treated.
• 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)
• Known hypersensitivity to fluorometholone or any of the excipients, in particular with benzalkonium chloride.
• Known hypersensitivity to dexamethasone phosphate or to any of the excipients
• Known hypersensitivity to tropicamide, atropine or its derivatives,
• Known hypersensitivity to phenylephrine, thiomersal

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Uveitis, Anterior

Interventions

isoniazid, pyrazinamide, rifampin drug combination; Ethambutol

Condition Hierarchy (Ancestors)

Panuveitis; Uveitis; Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals

Central Study Contacts

Georges Sélim TRAD

CONTACT

+33149095642; salim.trad@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 7, 2019
• Study Start: November 1, 2019
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: October 7, 2019

Record last verified: 2019-10