Clinical trial NCT02374060: PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial
Official title: PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Macular Edema
Uveitis
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2015-02-27
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the relative efficacy of three commonly utilized regional corticosteroids for the regional treatment of uveitic macular edema: periocular triamcinolone acetonide; intravitreal triamcinolone acetonide; intravitreal dexamethasone implant. The primary efficacy measure will be percent change in central subfield thickness as measured by OCT at 8 weeks. Participants will continue in the study for 24 weeks in order to evaluate relative effects of the 3 treatment strategies on the duration of treatment effects, requirement for additional injections, and adverse effects.

Note: The planned sample size for the POINT Trial was 267 subjects. On 17 July 2017, with 192 subjects enrolled, the Data and Safety Monitoring Committee (DSMC) reviewed the planned interim analysis and recommended that the goals of the trial could be accomplished by completing follow-up of enrolled subjects without the recruitment of additional subjects. Per the DSMC recommendations, recruitment was suspended and follow-up of enrolled subjects was completed according to the protocol.

Detailed description: Macular edema is the most common structural complication and leading cause of visual loss in patients with uveitis. Regional injections of corticosteroids are the most frequently used treatments specifically for uveitic macular edema but there is a lack of high quality evidence to guide choice of drug (e.g., triamcinolone acetonide, dexamethasone) and route of administration (e.g. periocular, intravitreal). The question of how to approach regional treatment of uveitic macular edema is a key question for ophthalmologists treating these patients. The Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema (POINT) Trial is a randomized trial designed to compare the relative efficacy of three regional corticosteroids commonly utilized for the initial regional treatment of uveitic macular edema, periocular triamcinolone (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX), and the intravitreal dexamethasone implant (Ozurdex®, Allergan, Irvine CA) will be conducted by the MUST Research Group clinical centers throughout the U.S. and one each in Australia and the UK. After signing informed consent and undergoing eligibility evaluation, eligible patients will be randomized to one of the three study treatments to be administered at the first study visit. Randomization is by participant, if both eyes meet eligibility requirements then both eyes receive assigned treatment. The design outcome is the percent change in central subfield macular thickness on OCT from baseline to the 8 week visit. After assessment of the primary outcome at 8 weeks, second injections and best medical judgment will be used if macular edema has not improved as follows:

Eye(s) meeting trial eligibility criteria receive initial injection of assigned treatment at P01 visit.

Second injection of assigned treatment permitted at 8 week visit for periocular triamcinolone and intravitreal triamcinolone and at 12 week visit for intravitreal dexamethasone if

* Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) or
* Eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield or
* ME is worse after initial improvement

And the following repeat injection criterion are met:

• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Eyes demonstrating no improvement or worsening of ME as measured by the central submacular thickness on OCT (at week 12 for periocular and intravitreal triamcinolone arms and at week 20 for intravitreal dexamethasone arm) are considered primary treatment non-responders.

Eligibility criteria: Inclusion Criteria:

Eye level inclusion criteria - at least one eye must meet all of the following conditions:

* Non-infectious anterior, intermediate, posterior or panuveitis; either active or inactive uveitis is acceptable;
* Macular edema (ME) defined as the presence of central subfield macular thickness greater than the normal range for the OCT machine being used, regardless of the presence of cysts, as assessed by study ophthalmologist;
* Best corrected visual acuity (BCVA) 5/200 or better;
* Baseline intraocular pressure \> 5 mm Hg and ≤ 21 mm Hg (current use of 3 or fewer intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable);
* Baseline fluorescein angiogram that is gradable for leakage in the central subfield
* Pupillary dilation sufficient to allow OCT testing.

Exclusion Criteria:

Patient level exclusion criteria:

-History of infectious uveitis, or of scleritis, keratitis, or infectious endophthalmitis in either eye;

History of central serous retinopathy in either eye;

* For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial;
* Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;
* Oral prednisone dose \> 10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤ 10 mg per day that has not been stable for at least 4 weeks(note that if patient is off of oral prednisone at baseline (P01 visit), dose stability requirement for past 4 weeks does not apply);
* Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks;
* Known allergy or hypersensitivity to any component of the study drugs;

Eye level exclusion criteria - at least one eye that meets all inclusion criteria cannot have any of the following conditions:

* History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥ 0.9 or any notching of optic nerve to the rim);
* Media opacity causing inability to assess fundus or perform OCT;
* Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (i.e., causing substantial wrinkling of the retinal surface)81;
* Torn or ruptured posterior lens capsule;
* Presence of silicone oil;
* Periocular or intravitreal corticosteroid injection in past 8 weeks;
* Injection of dexamethasone intravitreal implant in past 12 weeks;
* Placement of fluocinolone acetonide implant (Retisert) in past 3 years;

Primary outcomes:
measure: Proportion of Baseline Central Subfield Thickness Observed at 8 Weeks
timeFrame: At baseline and 8 weeks
Secondary outcomes:
measure: Proportion of Baseline Central Subfield Thickness Observed at 24 Weeks
timeFrame: At baseline and the 24 week visit
measure: Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks
timeFrame: Over 8 weeks of follow-up
measure: Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks
timeFrame: Over 24 weeks of follow-up
measure: Proportion of Eyes With Resolution of Macular Edema at 8 Weeks
timeFrame: Over 8 weeks of follow-up
measure: Proportion of Eyes With Resolution of Macular Edema at 24 Weeks
timeFrame: Over 24 weeks of follow-up
measure: Change in Best-corrected Visual Acuity at 8 Weeks
timeFrame: Over 8 weeks of follow-up
measure: Change in Best-corrected Visual Acuity at 24 Weeks
timeFrame: Over 24 weeks of follow-up
measure: Number of Eyes With Vitreous Hemorrhage
timeFrame: During 24 weeks of follow-up
measure: Number of Eyes With Retinal Tear or Detachment
timeFrame: During 24 weeks of follow-up
measure: Number of Eyes With Endophthalmitis
timeFrame: During 24 weeks of folllow-ip
measure: Cumulative Proportion of Eyes With Severe Vision Loss
timeFrame: During 24 weeks of follow-up
measure: Cumulative Proportion of Eyes With an IOP Elevation of >=10 mm Hg Over Baseline
timeFrame: During 24 weeks of follow-up
measure: Cumulative Proportion of Eyes With an IOP Elevation >=24 mm Hg
timeFrame: During 24 weeks of follow-up
measure: Cumulative Proportion of Eyes With an IOP Elevation >=30 mm Hg
timeFrame: During 24 weeks of follow-up
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute, UCLA
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Eye Institute, NIH
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: Rochester
country: United States
facility: MAYO Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: New York Eye and Ear Infirmary
state: New York
city: Durham
country: United States
facility: Duke Eye Center, Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: Scheie Eye Institute, University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Wills Eye Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Unniversity of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Vitreoretinal Consultants
state: Texas
city: Salt Lake City
country: United States
facility: John A. Moran Eye Center, University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: East Melbourne
country: Australia
facility: Royal Victorian Eye & Ear Hospital
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
Study officials:
affiliation: Icahn School of Medicine, Noutn Sinai, New York, NY
name: Douglas A Jabs, MD, MBA
role: STUDY_CHAIR
References:
citation: Thorne JE, Sugar EA, Holbrook JT, Burke AE, Altaweel MM, Vitale AT, Acharya NR, Kempen JH, Jabs DA; Multicenter Uveitis Steroid Treatment Trial Research Group. Periocular Triamcinolone vs. Intravitreal Triamcinolone vs. Intravitreal Dexamethasone Implant for the Treatment of Uveitic Macular Edema: The PeriOcular vs. INTravitreal corticosteroids for uveitic macular edema (POINT) Trial. Ophthalmology. 2019 Feb;126(2):283-295. doi: 10.1016/j.ophtha.2018.08.021. Epub 2018 Sep 27.