Cytomegalovirus Anterior UveitisPhase 2/3STACCATONCT03586284
Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes
A Phase 2/3 study testing Valganciclovir Hydrochloride and Ganciclovir Sodium in people with Cytomegalovirus Anterior Uveitis, run by University of California, San Francisco at 4 sites in 2 countries.
Trial summary
Cytomegalovirus (CMV) is generally a latent and asymptomatic infection in healthy, immunocompetent individuals. In immunocompromised patients CMV is well known to cause a retinitis that can lead to blindness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Anterior Uveitis
- What is being tested?
- Valganciclovir Hydrochloride and Ganciclovir Sodium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 15 Mar 2020to 13 Nov 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- pharmacologic, devices, barrier methods) or abstinence.
Who cannot join
- Patients <18 years of age
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Thailand3 sites
Chulalongkorn University
Bangkok
Chiang Mai University
Chiang Mai
Khon Kaen University
Khon Kaen
United States1 site
Proctor Foundation, UCSF
San Francisco, California, 94158
About this study
Official title: Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment
Cytomegalovirus (CMV) is generally a latent and asymptomatic infection in healthy, immunocompetent individuals. In immunocompromised patients CMV is well known to cause a retinitis that can lead to blindness. In immunocompetent patients, however, CMV can cause recurrent inflammation in the front of the eye (anterior uveitis). CMV anterior uveitis produces complications including pain, glaucoma, corneal failure, and vision loss. 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. Oral antiviral therapy of CMV carries blood and kidney side effects that requires laboratory monitoring. Topical therapy has been reported to be effective, but no consensus as to the appropriate drug concentration exists.
Here we propose a double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
Read the detailed description
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.
There are no studies comparing antivirals for the treatment of CMV anterior uveitis. However, multiple studies have utilized PCR to obtain an initial viral load before treating CMV anterior uveitis. The collective initial CMV viral load from these prior studies (39 patients in total) was approximately 600,000 IU/ml. There was minimal variation within studies in terms of initial viral load, but large variation between studies. To control for variability that can arise from different assays used or assays performed at different centers, we will perform all quantitative PCR at the same United States location. Even fewer studies have documented post-treatment viral loads. Many of the post-treatment PCR values showed undetectable viral loads, making it difficult to estimate viral load reduction trends between treatment groups. Of note, the limited data demonstrated that both intravenous ganciclovir and topical ganciclovir 2% groups showed significant and rapid reductions in viral load, almost always resulting in undetectable levels by 12 weeks, and occasionally as rapidly as 2-3 weeks. We identified three patients from the literature with CMV anterior uveitis that had detectable PCR values during the course of treatment. These patients had a 95% average reduction in viral load 14 days after treatment.
We are proposing a double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. The primary outcome will be percent reduction in viral load. We hypothesize that the oral valganciclovir arm will experience the greatest reduction in viral load. Secondary outcomes will include time to clinical quiescence and the effect of pre-enrollment topical corticosteroid use on initial viral load.
This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
- Conditions
- Cytomegalovirus Anterior Uveitis
- Being tested
- Valganciclovir Hydrochloride, Ganciclovir Sodium, Placebo Oral Tablet, Topical placebo
- Keywords
- Cytomegalovirus uveitis, Cytomegalovirus endotheliitis, Cytomegalovirus keratouveitis, Cytomegalovirus iridocyclitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valganciclovir HydrochlorideDrug
21 to 28 days of oral valganciclovir treatment
Ganciclovir SodiumDrug
21 to 28 days of topical ganciclovir solution treatment
Placebo Oral TabletDrug
21 to 28 days of placebo pill treatment
Topical placeboDrug
21 to 28 days of topical placebo treatment
| Study group | Role | What they receive |
|---|---|---|
| Oral Valganciclovir | Active comparator | Oral Valganciclovir 900mg PO BID Topical placebo solution, 1 drop applied 6 times daily Receives: Drug: Valganciclovir Hydrochloride; Drug: Topical placebo |
| Topical Ganciclovir 2% | Active comparator | Topical Ganciclovir 2% solution, 1 drop applied 6 times daily Placebo pills PO BID Receives: Drug: Ganciclovir Sodium; Drug: Placebo Oral Tablet |
| Placebo | Placebo comparator | Topical placebo solution, 1 drop applied 6 times daily Placebo pills PO BID Receives: Drug: Placebo Oral Tablet; Drug: Topical placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CMV Viral Load
Pre-treatment minus day-7 CMV DNA load in aqueous humor, reported as log10 IU/mL (WHO-standardized qPCR). Positive values indicate reduction.
Measured: 7 days
Secondary outcomes (2)
Number of Participants That Achieved Clinical Quiescence
Comparison between arms of percent that achieved clinical quiescence by final visit (anterior chamber cell ≤ 0.5+).
Measured: Day 0 to Day 21 (final visit)
Effect of Topical Corticosteroid
What effect did topical corticosteroid use prior to enrollment have on pre-treatment viral load (Day 0)
Measured: Day 0 (pre-treatment) viral load (IU/mL)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2018
- Study start15 Mar 2020
- Primary completion13 Nov 2024
- Study completion13 Nov 2024
Why it stopped: Funding discontinued.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus Anterior UveitisStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, double-masked, randomized, placebo-controlled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Huang Pacific Foundation, Khon Kaen University, King Chulalongkorn Memorial Hospital
- Responsible party
- Sponsor
- Investigators
- John A Gonzales, MD, Principal investigator, UCSF Proctor Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03586284
- Sponsor's protocol ID
- 18-24396
- Acronym
- STACCATO
- Status last verified
- Feb 2026
- First submitted
- 2 Jul 2018
- Last updated
- 5 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Takhar JS, Joye AS, Somkijrungroj T, Laovirojjanakul W, Lin CP, Lietman TM, Porco TC, Keenan JD, Gebreegziabher EA, Seitzman GD, Rose-Nussbaumer J, Doan TA, Acharya NR, Gonzales JA. A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol. BMJ Open. 2019 Dec 19;9(12):e033175. doi: 10.1136/bmjopen-2019-033175.
PubMed 31862739
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment
- ClinicalTrials.gov ID
- NCT03586284
- Acronym / sponsor ID
- STACCATO / 18-24396
- Conditions
- Cytomegalovirus Anterior Uveitis
- Keywords
- Cytomegalovirus uveitis, Cytomegalovirus endotheliitis, Cytomegalovirus keratouveitis, Cytomegalovirus iridocyclitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding discontinued.
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Huang Pacific Foundation, Khon Kaen University, King Chulalongkorn Memorial Hospital
- Study start
- 15 Mar 2020 (actual)
- Primary completion
- 13 Nov 2024 (actual)
- Study completion
- 13 Nov 2024 (actual)
- First posted
- 13 Jul 2018 (actual)
- Results
- Posted 10 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cytomegalovirus (CMV) is generally a latent and asymptomatic infection in healthy, immunocompetent individuals. In immunocompromised patients CMV is well known to cause a retinitis that can lead to blindness. In immunocompetent patients, however, CMV can cause recurrent inflammation in the front of the eye (anterior uveitis). CMV anterior uveitis produces complications including pain, glaucoma, corneal failure, and vision loss. 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. Oral antiviral therapy of CMV carries blood and kidney side effects that requires laboratory monitoring. Topical therapy has been reported to be effective, but no consensus as to the appropriate drug concentration exists.
Here we propose a double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
Detailed description
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.
There are no studies comparing antivirals for the treatment of CMV anterior uveitis. However, multiple studies have utilized PCR to obtain an initial viral load before treating CMV anterior uveitis. The collective initial CMV viral load from these prior studies (39 patients in total) was approximately 600,000 IU/ml. There was minimal variation within studies in terms of initial viral load, but large variation between studies. To control for variability that can arise from different assays used or assays performed at different centers, we will perform all quantitative PCR at the same United States location. Even fewer studies have documented post-treatment viral loads. Many of the post-treatment PCR values showed undetectable viral loads, making it difficult to estimate viral load reduction trends between treatment groups. Of note, the limited data demonstrated that both intravenous ganciclovir and topical ganciclovir 2% groups showed significant and rapid reductions in viral load, almost always resulting in undetectable levels by 12 weeks, and occasionally as rapidly as 2-3 weeks. We identified three patients from the literature with CMV anterior uveitis that had detectable PCR values during the course of treatment. These patients had a 95% average reduction in viral load 14 days after treatment.
We are proposing a double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. The primary outcome will be percent reduction in viral load. We hypothesize that the oral valganciclovir arm will experience the greatest reduction in viral load. Secondary outcomes will include time to clinical quiescence and the effect of pre-enrollment topical corticosteroid use on initial viral load.
This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Multicenter, double-masked, randomized, placebo-controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Oral Valganciclovir | Active comparator | Drug: Valganciclovir Hydrochloride, Drug: Topical placeboOral Valganciclovir 900mg PO BID Topical placebo solution, 1 drop applied 6 times daily |
| Topical Ganciclovir 2% | Active comparator | Drug: Ganciclovir Sodium, Drug: Placebo Oral TabletTopical Ganciclovir 2% solution, 1 drop applied 6 times daily Placebo pills PO BID |
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet, Drug: Topical placeboTopical placebo solution, 1 drop applied 6 times daily Placebo pills PO BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- pharmacologic, devices, barrier methods) or abstinence.
Key exclusion criteria (14 listed)
- Patients <18 years of age
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valganciclovir Hydrochloride21 to 28 days of oral valganciclovir treatment | Drug | Oral Valganciclovir |
| Ganciclovir Sodium21 to 28 days of topical ganciclovir solution treatment | Drug | Topical Ganciclovir 2% |
| Placebo Oral Tablet21 to 28 days of placebo pill treatment | Drug | Placebo, Topical Ganciclovir 2% |
| Topical placebo21 to 28 days of topical placebo treatment | Drug | Oral Valganciclovir, Placebo |
Primary outcome
Change in CMV Viral Load
Time frame: 7 days
Pre-treatment minus day-7 CMV DNA load in aqueous humor, reported as log10 IU/mL (WHO-standardized qPCR). Positive values indicate reduction.
2 secondary outcomes
Number of Participants That Achieved Clinical Quiescence
Time frame: Day 0 to Day 21 (final visit)
Effect of Topical Corticosteroid
Time frame: Day 0 (pre-treatment) viral load (IU/mL)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31862739Takhar JS, Joye AS, Somkijrungroj T, Laovirojjanakul W, Lin CP, Lietman TM, Porco TC, Keenan JD, Gebreegziabher EA, Seitzman GD, Rose-Nussbaumer J, Doan TA, Acharya NR, Gonzales JA. A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol. BMJ Open. 2019 Dec 19;9(12):e033175. doi: 10.1136/bmjopen-2019-033175.
- Individual participant dataSharing planned: No
Related trials for Cytomegalovirus Anterior Uveitis
Not yet recruitingPhase 2
Systemic and Topical Antiviral Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes - Trials I and II
Cytomegalovirus (CMV), Anterior Uveitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John A Gonzales, MD principal investigator
UCSF Proctor Foundation
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Valganciclovir Hydrochloride and Ganciclovir Sodium in people with Cytomegalovirus Anterior Uveitis, run by University of California, San Francisco at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Thailand, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in CMV Viral Load (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03586284, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.