Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis

Cytomegalovirus Infections Clinical Trial

— STACCATO  

Official title:

Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03576898
• Other study ID #: 18-24396
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: January 2019
• Est. completion date: April 2022

Study information

• Verified date: June 2018
• Source: Francis I. Proctor Foundation
• Contact: John A Gonzales, MD
• Phone: 415-502-2664
• Email: john.gonzales[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recurrent anterior uveitis in immunocompetent individuals can be caused by multiple members of the herpes virus group, including cytomegalovirus (CMV). Repeated bouts of CMV intraocular inflammation can be associated with ocular hypertension, glaucoma, pain, vision reduction or blindness. CMV anterior uveitis is commonly misdiagnosed as a non-infectious anterior uveitis and treated as such, which can beget further complications. Diagnosis requires directed polymerase chain reaction (PCR) testing. While antiviral therapy exists for CMV, identifying the appropriate therapy has been challenging because no randomized trials comparing routes of therapy (particularly oral or topical) have been performed. Currently, CMV anterior uveitis is typically treated with oral valganciclovir in the United States but carries the risk of serious systemic side effects that necessitate laboratory monitoring. There is evidence that suggests topical ganciclovir can be used to treat and prevent recurrences of CMV anterior uveitis, though the appropriate concentration is not well defined. Topical ganciclovir is attractive because it does not require laboratory monitoring, though a unique side effect profile that includes corneal epitheliopathy and conjunctivitis may preclude long-term use. While anterior chamber paracentesis with polymerase chain reaction (PCR) testing demonstrates CMV during an initial flare of inflammation, it is unknown whether repeated recurrences of inflammation are mediated by viral re-infection and replication in the anterior chamber or if a sterile immune response is at play. Consequently, patients may be submitted to many years of oral or topical antiviral therapy. This strategy poses challenges without proper evaluation of the multiple treatment and long-term management approaches. Further studies are needed to elucidate the most appropriate antiviral therapies that balance efficacy and toxicity while treating CMV anterior uveitis.

We hypothesize that the efficacy of oral valganciclovir in the treatment of cytomegalovirus (CMV) anterior uveitis will be greater when compared to topical or placebo treatments.

This study will be a multicenter, double-masked, randomized, placebo-controlled clinical trial.

Description:

Specific Aims of the Project:

1a. To assess reduction in CMV viral load at 7 days after randomization to treatment with oral or topical antiviral. We hypothesize that the greatest reduction in viral load will be with oral valganciclovir 900 mg PO BID compared to topical ganciclovir 2% every 2 hours daily and placebo.

1b. To assess intraocular drug concentration at 7 days after randomization to treatment with oral or topical antiviral. We hypothesize that the greatest concentration of drug within the anterior chamber fluid will be found with oral valganciclovir 900 mg PO BID compared to topical ganciclovir and placebo.

1c. To assess the percentage of patients with clinical quiescence after randomization to 28 days of treatment. We hypothesize that the proportion of patients that have achieved clinical quiescence at 28 days will be higher with oral valganciclovir compared to topical ganciclovir and placebo.

1d. To evaluate the effect of topical corticosteroid started prior to eligibility screening on diagnostic yield of PCR. We hypothesize that the yield of virus will be positively correlated with increased frequency of use of topical corticosteroids.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 99
• Est. completion date: April 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical impression consistent with CMV anterior uveitis

• Directed PCR positive for CMV OR previous PCR-proven CMV anterior uveitis

• Willingness to use an acceptable method of contraception during the study period (i.e. pharmacologics, devices, barrier methods) or abstinence.

Exclusion Criteria:

• Patients <18 years of age (<20 years of age in Taiwan)

• Intermediate or posterior inflammation (involvement of vitreous, choroid, or retina)

• Received antiviral therapy <14 days prior to enrollment

• Received periocular or intraocular corticosteroid injection < 8 weeks prior to enrollment

• Currently taking oral corticosteroids

• Immunocompromised (primary or secondary immunosuppressive disorders)

• Prior immunosuppressive therapy in the past 6 months

• Directed PCR negative for CMV

• Directed PCR positive for herpes simplex virus (HSV) or varicella zoster virus (VZV)

• Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females of child-bearing age is mandatory within 4 weeks prior to enrollment)

• Complete blood count with white blood cell, absolute neutrophil, or platelet count lower than the lower limit of reference laboratory normal

• BUN or Cr above the upper limit of reference laboratory normal

• Recent ocular surgery within the past 30 days, or planned surgery within the next 45 days

• Systemic autoimmune disease or ocular condition (besides anterior uveitis) anticipated to dictate or alter treatment course

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Iridocyclitis
• Uveitis
• Uveitis, Anterior

Intervention

Drug:
• Topical ganciclovir versus oral valganciclovir versus placebo
Viral load reduction prior to randomization will be compared between the arms (topical ganciclovir 2% applied into affected eye every 2 hours versus oral valganciclovir 900 mg orally twice daily versus placebo).

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Francis I. Proctor Foundation	Chulalongkorn University, Khon Kaen University, National Taiwan University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMV viral load reduction at 7 days after randomization to treatment with oral or topical antiviral.	CMV viral load	7 days