PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial

NCT02374060 | Completed Phase 3 Results DMC

• 2 other identifiers: IRB000061391U10EY024527-01
• Study Type: interventional
• Target: 192
• Locations: 4 countries
• Sites: 26

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.

Conditions

Macular Edema; Uveitis

Outcome Measures

Primary Outcomes (1)

• Proportion of Baseline Central Subfield Thickness Observed at 8 Weeks

  The primary outcome is the change in central subfield thickness from baseline to 8 weeks measured on a relative scale as the the proportion of the baseline central subfield thickness. Values less than 1 indicate a decrease in retinal thickness with lower values indicating greater decreases. Smaller values are better. The time point of 8 weeks was chosen for assessment of the primary outcome because it encompasses the window for maximum benefit for all three treatment strategies. Retinal thickness was evaluated using masked assessments of OCT images.

  At baseline and 8 weeks

Secondary Outcomes (14)

• Proportion of Baseline Central Subfield Thickness Observed at 24 Weeks

  At baseline and the 24 week visit

• Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks

  Over 8 weeks of follow-up

• Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks

  Over 24 weeks of follow-up

• Proportion of Eyes With Resolution of Macular Edema at 8 Weeks

  Over 8 weeks of follow-up

• Proportion of Eyes With Resolution of Macular Edema at 24 Weeks

  Over 24 weeks of follow-up

Study Arms (3)

Periocular triamcinolone 40mg

ACTIVE COMPARATOR

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;

Drug: Periocular triamcinolone 40 mg

Intravitreal triamcinolone 4mg

ACTIVE COMPARATOR

(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;

Drug: Intravitreal triamcinolone 4 mg

Dexamethasoneintravitreal implant

ACTIVE COMPARATOR

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;

Drug: Dexamethasone intravitreal implant

Interventions

Periocular triamcinolone 40 mg 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.

Also known as: Kenalog

Periocular triamcinolone 40mg

Intravitreal triamcinolone 4 mg 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.

Also known as: Triescence (in U.S); Kenalog allowed at non-U.S. clinics

Intravitreal triamcinolone 4mg

Dexamethasone intravitreal implant DRUG

• Standard preparation as described for intravitreal injections.

Also known as: Ozurdex

Dexamethasoneintravitreal implant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• JHSPH Center for Clinical Trials: lead
• National Eye Institute (NEI): collaborator

Study Sites (26)

Jules Stein Eye Institute, UCLA

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

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

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

National Eye Institute, NIH

Bethesda, Maryland, 20892, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

MAYO Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Eye and Ear Infirmary

New York, New York, 10016, United States

Location

Duke Eye Center, Duke University

Durham, North Carolina, 27710, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Unniversity of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Vitreoretinal Consultants

Houston, Texas, 77030, United States

Location

John A. Moran Eye Center, University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Royal Victorian Eye & Ear Hospital

East Melbourne, Australia

Location

McGill University

Montreal, Quebec, H4A 3s5, Canada

Location

Moorfields Eye Hospital

London, EC1V 9EL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30269924 RESULT

MeSH Terms

Conditions

Macular Edema; Uveitis

Interventions

Triamcinolone Acetonide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienetriols; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Elizabeth Sugar, PhD
• Organization: Johns Hopkins University

esugar2@jhu.edu

(410) 614-7837

Study Officials

• Douglas A Jabs, MD, MBA

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: February 27, 2015
• Study Start: June 16, 2015
• Primary Completion: August 30, 2017
• Study Completion: January 4, 2018
• Last Updated: December 4, 2018
• Results First Posted: November 5, 2018

Record last verified: 2018-05

Locations

AU (1); GB (1); US (23); CA (1)