UveitisPhase 3FASTNCT01232920
First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial
A Phase 3 study testing Methotrexate and Mycophenolate mofetil in people with Uveitis, run by University of California, San Francisco at 2 sites in India.
Trial summary
The proposed study is a masked trial, with stratified block randomization by site, designed to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line steroid-sparing treatment for patients with non-infectious uveitis requiring corticosteroid-sparing therapy. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Uveitis
- What is being tested?
- Methotrexate and Mycophenolate mofetil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesIndia
- Study dates
- Oct 2010to Jun 2012
- Phase
- Phase 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Non-infectious anterior, intermediate, posterior or panuveitis
- Active uveitis within the last 60 days (defined by the presence of any of the following according to SUN criteria: ≥ 1+ anterior chamber cells, anterior vitreous cells, vitreous haze, active retinal or choroidal lesions)
- Prednisone dose ≥ 15 mg/day
- History of corticosteroid taper failure (inability to taper to prednisone 10 mg or less) or obvious chronic disease necessitating corticosteroid-sparing immunosuppressive treatment
Who cannot join
- Any infectious cause of uveitis
- Tuberculosis: Evidence of active TB (PPD and CXR required - latent TB patients are still eligible)
- Positive for Hepatitis: HBsAg and/or Hep C antibody
- Positive for Syphilis: RPR/VDRL and/or FTA-ABS
- Abnormal CBC (<2500 WBC or <75,000 Plts or <10 Hgb)
- Abnormal liver and/or kidney tests (ALT/AST >2x normal or CR>1.5)
Show all 15Show fewer
- Pregnancy or breast-feeding (blood or urine pregnancy test for all females, excluding those who are post-menopausal)
- Chronic hypotony (IOP < 5 mm Hg for > 3 months)
- Prior use of any immunosuppressive drug for the treatment of uveitis in the past 6 months
- Prior failed treatment with methotrexate or mycophenolate mofetil
- Periocular or intravitreal corticosteroid injection in the past 3 months
- Fluocinolone acetonide implant surgery in either eye in < 3 years
- Intraocular surgery in < 30 days, or any ocular surgery scheduled during the 6-month study period
- VA of hand motions or worse in better eye
- < 16 years of age at enrollment
Trial locations and contacts
2 sites in 1 country.
India2 sites
Aravind Eye Hospital
Coimbatore, Tamil Nadu
Aravind Eye Hospital
Madurai, Tamil Nadu
About this study
The proposed study is a masked trial, with stratified block randomization by site, designed to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line steroid-sparing treatment for patients with non-infectious uveitis requiring corticosteroid-sparing therapy.
One hundred non-infectious uveitis patients in need of corticosteroid-sparing therapy will be randomized to receive either oral methotrexate or oral mycophenolate mofetil at Aravind Eye Hospitals (Madurai and Coimbatore, South India). They will be followed monthly for 6 months after enrollment or until treatment failure. The investigators hypothesize that the proportion achieving corticosteroid-sparing success at 6 months for patients taking mycophenolate mofetil will be improved in comparison with patients taking methotrexate.
Read the detailed description
Uveitis, a set of conditions defined by intraocular inflammation, is a significant cause of vision loss and morbidity in the United States and the world. The incidence was recently estimated to be more than 50 cases per 100,000 person-years, with a prevalence of approximately 115 per 100,000 persons. Additionally, uveitis is believed to be the cause of up to 10% of cases of legal blindness in the United States, or approximately 30,000 new cases of blindness per year. In contrast to common age-related eye disorders, uveitis may have a stronger socio-economic impact because it disproportionately affects younger working-age patients. Although the etiology of uveitis is varied, most cases are presumed to be immune-mediated and lack a known infectious cause. Even in developing countries such as India that have a larger burden of infection, the vast majority of cases are non-infectious.
The current mainstay of treatment for noninfectious uveitis is corticosteroids (topical, systemic, locally injected, or corticosteroid-eluting implants). Due to the well documented local and systemic side effects associated with corticosteroid therapy, other immunosuppressive therapies are frequently used as corticosteroid-sparing agents in patients who need long-term therapy. These include antimetabolites, calcineurin inhibitors, alkylating agents, and biologic drugs. Cost and morbidity associated with uncontrolled inflammation make the selection of an effective initial steroid-sparing agent extremely important.
It is common practice for patients requiring a steroid-sparing agent to be treated first with the less expensive methotrexate and then switched to mycophenolate mofetil in the event of treatment failure. However, results from non-comparative retrospective case series indicate that uveitis patients may be much more likely to achieve controlled inflammation and tolerate treatment with mycophenolate mofetil. Furthermore, approximately half of the patients who fail treatment with methotrexate go on to successful treatment with mycophenolate mofetil. There have been no prospective randomized, controlled trials to systematically determine which antimetabolite is more clinically efficacious as initial corticosteroid-sparing therapy, making it difficult for clinicians to make informed, evidence-based decisions about first-line immunosuppressive treatment.
Our contribution is expected to be a definitive understanding of the comparative efficacy, tolerability, and quality of life of these two antimetabolites as initial steroid-sparing therapy for uveitis patients requiring chronic therapy. This contribution is significant because it will enable clinicians to make evidence-based decisions when prescribing first-line immunosuppressive therapy for their uveitis patients. The use of optimal first-line therapy will improve quality of life by reducing the risk of vision loss and complications associated with uncontrolled ocular inflammation and long-term corticosteroid use.
- Conditions
- Uveitis
- Being tested
- Methotrexate, Mycophenolate mofetil
- Keywords
- uveitis, antimetabolite, immunosuppressive, clinical trial
- Medical subject headings
- Uveitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.
Also called Cellcept
Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate | Active comparator | Not described Receives: Drug: Methotrexate |
| Mycophenolate mofetil | Active comparator | Not described Receives: Drug: Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving Treatment Success
TREATMENT SUCCESS is defined as controlled ocular inflammation in both eyes with less than or equal to 10 mg/day of prednisone and/or 2 topical steroid drops/day sustained for 2 visits separated by at least 28 days (control of inflammation and prednisone dose must be achieved by 5-month visit and sustained until 6-month visit).
Discontinuation of study medication at any time due to efficacy, tolerability, or safety may result in a declaration of TREATMENT FAILURE. Note that all patients will be classified as either a treatment success or failure.
Measured: 6 months
Secondary outcomes (3)
Time to Control of Inflammation
Measured: 6 months
Change in Best Spectacle-corrected Visual Acuity (BSCVA)
Change in best spectacle-corrected visual acuity (BSCVA) from baseline. Analysis on eye level
Measured: 6 months
Number of Eyes With Resolution of Macular Edema
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2012
- Study completionJun 2012
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 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Responsible party
- Sponsor
- Investigators
- S R Rathinam, MD, Principal investigator, Aravind Eye HospitalM B Babu, MD, Principal investigator, Aravind Eye HospitalNisha Acharya, MD MS, Principal investigator, Proctor Foundation, UCSF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01232920
- Sponsor's protocol ID
- 10-00235
- Acronym
- FAST
- Status last verified
- Jun 2016
- First submitted
- 1 Nov 2010
- Last updated
- 15 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Niemeyer KM, Gonzales JA, Rathinam SR, Babu M, Thundikandy R, Kanakath A, Porco TC, Browne EN, Rao MM, Acharya NR. Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing Antimetabolites for Intermediate, Posterior, and Panuveitis. Am J Ophthalmol. 2017 Jul;179:10-17. doi: 10.1016/j.ajo.2017.04.003. Epub 2017 Apr 14.
PubMed 28414043
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial
- ClinicalTrials.gov ID
- NCT01232920
- Acronym / sponsor ID
- FAST / 10-00235
- Conditions
- Uveitis
- Keywords
- uveitis, antimetabolite, immunosuppressive, clinical trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Study start
- Oct 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 2 Nov 2010 (estimated)
- Results
- Posted 5 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is a masked trial, with stratified block randomization by site, designed to determine which treatment, methotrexate or mycophenolate mofetil, is more effective as first-line steroid-sparing treatment for patients with non-infectious uveitis requiring corticosteroid-sparing therapy.
One hundred non-infectious uveitis patients in need of corticosteroid-sparing therapy will be randomized to receive either oral methotrexate or oral mycophenolate mofetil at Aravind Eye Hospitals (Madurai and Coimbatore, South India). They will be followed monthly for 6 months after enrollment or until treatment failure. The investigators hypothesize that the proportion achieving corticosteroid-sparing success at 6 months for patients taking mycophenolate mofetil will be improved in comparison with patients taking methotrexate.
Detailed description
Uveitis, a set of conditions defined by intraocular inflammation, is a significant cause of vision loss and morbidity in the United States and the world. The incidence was recently estimated to be more than 50 cases per 100,000 person-years, with a prevalence of approximately 115 per 100,000 persons. Additionally, uveitis is believed to be the cause of up to 10% of cases of legal blindness in the United States, or approximately 30,000 new cases of blindness per year. In contrast to common age-related eye disorders, uveitis may have a stronger socio-economic impact because it disproportionately affects younger working-age patients. Although the etiology of uveitis is varied, most cases are presumed to be immune-mediated and lack a known infectious cause. Even in developing countries such as India that have a larger burden of infection, the vast majority of cases are non-infectious.
The current mainstay of treatment for noninfectious uveitis is corticosteroids (topical, systemic, locally injected, or corticosteroid-eluting implants). Due to the well documented local and systemic side effects associated with corticosteroid therapy, other immunosuppressive therapies are frequently used as corticosteroid-sparing agents in patients who need long-term therapy. These include antimetabolites, calcineurin inhibitors, alkylating agents, and biologic drugs. Cost and morbidity associated with uncontrolled inflammation make the selection of an effective initial steroid-sparing agent extremely important.
It is common practice for patients requiring a steroid-sparing agent to be treated first with the less expensive methotrexate and then switched to mycophenolate mofetil in the event of treatment failure. However, results from non-comparative retrospective case series indicate that uveitis patients may be much more likely to achieve controlled inflammation and tolerate treatment with mycophenolate mofetil. Furthermore, approximately half of the patients who fail treatment with methotrexate go on to successful treatment with mycophenolate mofetil. There have been no prospective randomized, controlled trials to systematically determine which antimetabolite is more clinically efficacious as initial corticosteroid-sparing therapy, making it difficult for clinicians to make informed, evidence-based decisions about first-line immunosuppressive treatment.
Our contribution is expected to be a definitive understanding of the comparative efficacy, tolerability, and quality of life of these two antimetabolites as initial steroid-sparing therapy for uveitis patients requiring chronic therapy. This contribution is significant because it will enable clinicians to make evidence-based decisions when prescribing first-line immunosuppressive therapy for their uveitis patients. The use of optimal first-line therapy will improve quality of life by reducing the risk of vision loss and complications associated with uncontrolled ocular inflammation and long-term corticosteroid use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate | Active comparator | Drug: Methotrexate |
| Mycophenolate mofetil | Active comparator | Drug: Mycophenolate mofetil |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Non-infectious anterior, intermediate, posterior or panuveitis
- Active uveitis within the last 60 days (defined by the presence of any of the following according to SUN criteria: ≥ 1+ anterior chamber cells, anterior vitreous cells, vitreous haze, active retinal or choroidal lesions)
- Prednisone dose ≥ 15 mg/day
- History of corticosteroid taper failure (inability to taper to prednisone 10 mg or less) or obvious chronic disease necessitating corticosteroid-sparing immunosuppressive treatment
Key exclusion criteria (15 listed)
- Any infectious cause of uveitis
- Tuberculosis: Evidence of active TB (PPD and CXR required - latent TB patients are still eligible)
- Positive for Hepatitis: HBsAg and/or Hep C antibody
- Positive for Syphilis: RPR/VDRL and/or FTA-ABS
- Abnormal CBC (<2500 WBC or <75,000 Plts or <10 Hgb)
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 |
|---|---|---|
| MethotrexateAll methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week. | Drug | Methotrexate |
| Mycophenolate mofetilAlso: CellceptMycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID. | Drug | Mycophenolate mofetil |
Primary outcome
Number of Participants Achieving Treatment Success
Time frame: 6 months
TREATMENT SUCCESS is defined as controlled ocular inflammation in both eyes with less than or equal to 10 mg/day of prednisone and/or 2 topical steroid drops/day sustained for 2 visits separated by at least 28 days (control of inflammation and prednisone dose must be achieved by 5-month visit and sustained until 6-month visit). Discontinuation of study medication at any time due to efficacy, tolerability, or safety may result in a declaration of TREATMENT FAILURE. Note that all patients will be classified as either a treatment success or failure.
3 secondary outcomes
Time to Control of Inflammation
Time frame: 6 months
Change in Best Spectacle-corrected Visual Acuity (BSCVA)
Time frame: 6 months
Number of Eyes With Resolution of Macular Edema
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28414043Niemeyer KM, Gonzales JA, Rathinam SR, Babu M, Thundikandy R, Kanakath A, Porco TC, Browne EN, Rao MM, Acharya NR. Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing Antimetabolites for Intermediate, Posterior, and Panuveitis. Am J Ophthalmol. 2017 Jul;179:10-17. doi: 10.1016/j.ajo.2017.04.003. Epub 2017 Apr 14.
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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.
S R Rathinam, MD principal investigator
Aravind Eye Hospital
M B Babu, MD principal investigator
Aravind Eye Hospital
Nisha Acharya, MD MS principal investigator
Proctor Foundation, UCSF
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate and Mycophenolate mofetil in people with Uveitis, run by University of California, San Francisco at 2 sites in India.
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 15 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: finished, as of the sponsor's last update on 15 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 5 Jan 2016). 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?
Number of Participants Achieving Treatment Success (time frame: 6 months). 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 NCT01232920, 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 15 Jul 2016.