PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial

NCT ID: NCT02374060

Last Updated: 2018-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-16
• Study Completion Date: 2018-01-04

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.

Conditions

Macular Edema; Uveitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Periocular triamcinolone 40mg

Periocular triamcinolone acetonide (Kenalog), 40 mg Initial injection at Week 0

Second injection permitted at Week 8 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;
• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Group Type: ACTIVE_COMPARATOR

Periocular triamcinolone 40 mg

Intervention Type: DRUG

Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed.

Intravitreal triamcinolone 4mg

(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg) Initial injection at Week 0

Second injection permitted at Week 8 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;
• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Group Type: ACTIVE_COMPARATOR

Intravitreal triamcinolone 4 mg

Intervention Type: DRUG

Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.

Dexamethasoneintravitreal implant

Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) Initial injection at Week 0

Second injection permitted at Week 12 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;
• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Group Type: ACTIVE_COMPARATOR

Dexamethasone intravitreal implant

Intervention Type: DRUG

• Standard preparation as described for intravitreal injections.

Interventions

Periocular triamcinolone 40 mg

Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed.

Intervention Type: DRUG

Intravitreal triamcinolone 4 mg

Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.

Intervention Type: DRUG

Dexamethasone intravitreal implant

• Standard preparation as described for intravitreal injections.

Intervention Type: DRUG

Other Intervention Names

Kenalog; Triescence (in U.S); Kenalog allowed at non-U.S. clinics; Ozurdex

Eligibility Criteria

Inclusion Criteria

• 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.

• 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;

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

JHSPH Center for Clinical Trials

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas A Jabs, MD, MBA

Role: STUDY_CHAIR

Icahn School of Medicine, Noutn Sinai, New York, NY

Locations

Jules Stein Eye Institute, UCLA

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Johns Hopkins University

Baltimore, Maryland, United States

National Eye Institute, NIH

Bethesda, Maryland, United States

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, United States

MAYO Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

New York Eye and Ear Infirmary

New York, New York, United States

Duke Eye Center, Duke University

Durham, North Carolina, United States

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, United States

Wills Eye Hospital

Philadelphia, Pennsylvania, United States

Unniversity of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vitreoretinal Consultants

Houston, Texas, United States

John A. Moran Eye Center, University of Utah

Salt Lake City, Utah, United States

University of Washington

Seattle, Washington, United States

Royal Victorian Eye & Ear Hospital

East Melbourne, , Australia

McGill University

Montreal, Quebec, Canada

Moorfields Eye Hospital

London, , United Kingdom

Countries

United States; Australia; Canada; United Kingdom

References

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.

Reference Type: RESULT

PMID: 30269924 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1U10EY024527-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00006139

Identifier Type: -

Identifier Source: org_study_id