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Clinical Trials
March 2007

Effect of Ruboxistaurin in Patients With Diabetic Macular EdemaThirty-Month Results of the Randomized PKC-DMES Clinical Trial

Author Affiliations

ROY W.BECKMD, PhDEverett Ai MD, San Francisco, Calif; Lloyd M.Aiello MD, PhD, Boston, Mass; Rajiv Anand MD, Dallas, Tex; Mark Blumenkranz MD, Menlo Park, Calif; David Boyer MDgrees>, Beverly Hills, Calif; Alexander J. Brucker MD, Philadelphia, Pa; Thomas Chandler MD, Austin, Tex; Lawrence Chong MD, Los Angeles, Calif; Thomas Connor MD, Milwaukee, Wis; Ron Danis MD, Madison, Wis; Doug Dehning MD, Independence, Mo; Paul Dodson MD, Birmingham, England; Alexander Eaton MD, Ft Myers, Fla; David Faber MD, Salt Lake City, Utah; Dan Finkelstein MD, Baltimore, Md; John V. Forrester MD, Aberdeen, Scotland; Robert N. Frank MD, Detroit, Mich; Charles Garcia MD, Houston, Tex; Thomas W. Gardner MD, Hershey, Pa; Karen M. Gehrs MD, Iowa City, Iowa; Roy A. Goodart MD, Salt Lake City; Justin Gottlieb MD, Madison; Craig M. Greven MD, Winston-Salem, NC; David R. Guyer MD, New York, NY; Dean Hainsworth MD, Columbia, Mo; Philip Hooper MD, London, Ontario; William E. Jackson MD, Denver, Colo; James L. Kinyoun MD, Seattle, Wash; Mark Kipnes MD, San Antonio, Tex; Michael L. Klein MD, Portland, Ore; Eva M. Kohner MD, London, England; Baruch Kuppermann MD, Irvine, Calif; Hilel Lewis MD, Cleveland, Ohio; Helen K. Li MD, Galveston, Tex; Henrik Lund-Andersen MD, Herlev, Denmark; Colin Ma MD, Portland; Daniel F. Martin MD, Atlanta, Ga; Juan Orellana MD, Wake Forest, NC; Philip Y. Paden MD, Medford, Ore; Bettine Polak MD, PhD, Amsterdam, the Netherlands; Stuart A. Ross MD, Calgary, Alberta; George Sharuk, Boston, Mass; Lawrence J. Singerman MD, Clevelend, Ohio; William E. Smiddy MD, Miami, Fla; Michael Trese MD, OD, Royal Oak, Mich; James P. Tweeten MD, Boise, Idaho; Andrew Vine MD, Ann Arbor, Mich; Jiten Vora MD, Liverpool, England; Bruce Wolffenbuttel MD, Maastricht, the Netherlands. Authors/Writing Committee: Lloyd Paul Aiello, MD, PhD, Boston, Mass; Matthew D. Davis, MD, Madison, Wis; Aniz Girach, Indianapolis, Ind; Kuolung Hu, MS, Indianapolis; Roy C. Milton, PhD, Rockville, Md; Matthew J. Sheetz, MD, PhD, Indianapolis; Louis Vignati, MD, Indianapolis.

Arch Ophthalmol. 2007;125(3):318-324. doi:10.1001/archopht.125.3.318

Objective  To evaluate the safety and efficacy of orally administered ruboxistaurin (RBX) as a mesylate salt in patients with diabetic macular edema (DME).

Design  Multicenter, double-masked, randomized, placebo-controlled study of 686 patients receiving placebo or RBX orally (4, 16, or 32 mg/d) for 30 months. At baseline, patients had DME farther than 300 μm from the center of the macula, an Early Treatment Diabetic Retinopathy Study retinopathy severity level from 20 to 47A without prior photocoagulation, and an Early Treatment Diabetic Retinopathy Study visual acuity of 75 or more letters in the study eye. The primary study outcome was progression to sight-threatening DME or application of focal/grid photocoagulation for DME.

Main Outcome Measure  Masked grading of stereoscopic fundus photographs.

Results  The delay in progression to the primary outcome was not statistically significant (32 mg of RBX vs placebo, P = .14 [unadjusted]; Cox proportional hazards model adjusted for covariates, hazards ratio = 0.73; 95% confidence interval, 0.53-1.0; P = .06). However, application of focal/grid photocoagulation prior to progression to sight-threatening DME varied by site, and a secondary analysis of progression to sight-threatening DME alone showed that 32 mg of RBX per day reduced progression, compared with placebo (P = .054 [unadjusted]; Cox proportional hazards model, hazards ratio = 0.66; 95% confidence interval, 0.47-0.93; P = .02).

Conclusions  Although progression to the primary outcome was not delayed, daily oral administration of RBX may delay progression of DME to a sight-threatening stage. Ruboxistaurin was well tolerated in this study.