Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema
David S Boyer, Young Hee Yoon, Rubens Belfort Jr, Francesco Bandello, Raj K Maturi, Albert J Augustin, Xiao-Yan Li, Harry Cui, Yehia Hashad, Scott M Whitcup, Ozurdex MEAD Study Group, Suel Abujamra, James Acton, Fareed Ali, Andrew Antoszyk, Albert J Augustin, Carl C Awh, Adiel Barak, Karl Ulrich Bartz-Schmidt, Caroline R Baumal, Rubens Belfort Jr, Muna Bhende, David S Boyer, William Z Bridges Jr, David M Brown, Trevor Carmichael, Ken Carnevale, Antonio M Casella, Tom Chang, Daniel Chechik, San-Ni Chen, Lawrence P Chong, Victor Chong, Joel Corwin, Catherine Creuzot-Garcher, Alan Cruess, Mark Daniell, Marcos P de Avila, Haroldo Vieira de Moraes Jr, Robert G Devenyi, Bernard H Doft, Mark Donaldson, Richard Dreyer, Dean Eliott, Harry M Engel, Jan Ernest, Thomas F Essman, Philip M Falcone, Sharon Fekrat, Joseph R Ferencz, Joao L Ferreira, Joao Figueira, Ivan Fiser, Bradley Foster, Gregory M Fox, William R Freeman, S P Garg, Mark Gillies, David Glaser, Burton G Goldstein, Andre M V Gomes, John R Gonder, Lingam Gopal, Petrus Gous, Amod Gupta, Anurag Gupta, Lawrence Halperin, Dennis Han, Seenu M Hariprasad, Frank G Holz, Peter Kaiser, Bohdana Kalvodova, Barrett Katz, Randy S Katz, Dariusz Kecik, Judianne Kellaway, Itamar Klemperer, Baruch Kuppermann, Paolo Lanzetta, Rosangela Lattanzio, Won-Ki Lee, John Lehr, Monique Leys, Isaac Loose, Andrew Lotery, Da-Wen Lu, Paul McCartney, Ajit B Majji, Jose A Martinez, Pascale Massin, Raj K Maturi, Ugo Menchini, Geeta Menon, Mark Michels, Edoardo Midena, James Miller Jr, Paul Mitchell, Joseph Moisseiev, Lawrence Morse, Rafael Navarro, Janos Nemeth, Henry Newland, Richard Newsom, John Nichols, Juan Orellana, Nicola Orzalesi, Augusto Paranhos Jr, Robert Park, Susanna Park, Maurizio Battaglia Parodi, Peter R Pavan, James Peace, Don J Perez-Ortiz, Ayala Pollack, Kim Ramaswamy, Ramakrishna Ratnakaram, Giuseppe Ravalico, Jiri Rehak, Kourous Rezaei, Stanislao Rizzo, Francisco J Rodriguez-Alvira, Jean-Paul Romanet, Steven Rose, Richard B Rosen, Luca Rossetti, Jose Maria Ruiz-Moreno, SriniVas Sadda, Kenneth Sall, Dirk Sandner, Alvaro Fernandez-Vega Sanz, Gil Sartani, Stefanie Schmickler, Steven D Schwartz, Y R Sharma, Shwu-Jiuan Sheu, Michael Singer, Sobha Sivaprasad, Gisele Soubrane, Petr Soucek, Eric H Souied, Giovanni Staurenghi, Jan Studnicka, Marta Suarez-Figueroa, Walter Y Takahashi, Daniele Tognetto, Patrick L Tsai, Lawrence J Ulanski 2nd, Harvey Uy, Monica Varano, Miroslav Veith, Igor Vicha, Francesco Viola, Linda Visser, Dov Weinberger, Glenn L Wing, Edmund Wong, Tien Wong, Edward Wylegala, Jiong Yan, Young Hee Yoon, Lucy H Young, Hyeong G Yu, Ingrid E Zimmer-Galler, David S Boyer, Young Hee Yoon, Rubens Belfort Jr, Francesco Bandello, Raj K Maturi, Albert J Augustin, Xiao-Yan Li, Harry Cui, Yehia Hashad, Scott M Whitcup, Ozurdex MEAD Study Group, Suel Abujamra, James Acton, Fareed Ali, Andrew Antoszyk, Albert J Augustin, Carl C Awh, Adiel Barak, Karl Ulrich Bartz-Schmidt, Caroline R Baumal, Rubens Belfort Jr, Muna Bhende, David S Boyer, William Z Bridges Jr, David M Brown, Trevor Carmichael, Ken Carnevale, Antonio M Casella, Tom Chang, Daniel Chechik, San-Ni Chen, Lawrence P Chong, Victor Chong, Joel Corwin, Catherine Creuzot-Garcher, Alan Cruess, Mark Daniell, Marcos P de Avila, Haroldo Vieira de Moraes Jr, Robert G Devenyi, Bernard H Doft, Mark Donaldson, Richard Dreyer, Dean Eliott, Harry M Engel, Jan Ernest, Thomas F Essman, Philip M Falcone, Sharon Fekrat, Joseph R Ferencz, Joao L Ferreira, Joao Figueira, Ivan Fiser, Bradley Foster, Gregory M Fox, William R Freeman, S P Garg, Mark Gillies, David Glaser, Burton G Goldstein, Andre M V Gomes, John R Gonder, Lingam Gopal, Petrus Gous, Amod Gupta, Anurag Gupta, Lawrence Halperin, Dennis Han, Seenu M Hariprasad, Frank G Holz, Peter Kaiser, Bohdana Kalvodova, Barrett Katz, Randy S Katz, Dariusz Kecik, Judianne Kellaway, Itamar Klemperer, Baruch Kuppermann, Paolo Lanzetta, Rosangela Lattanzio, Won-Ki Lee, John Lehr, Monique Leys, Isaac Loose, Andrew Lotery, Da-Wen Lu, Paul McCartney, Ajit B Majji, Jose A Martinez, Pascale Massin, Raj K Maturi, Ugo Menchini, Geeta Menon, Mark Michels, Edoardo Midena, James Miller Jr, Paul Mitchell, Joseph Moisseiev, Lawrence Morse, Rafael Navarro, Janos Nemeth, Henry Newland, Richard Newsom, John Nichols, Juan Orellana, Nicola Orzalesi, Augusto Paranhos Jr, Robert Park, Susanna Park, Maurizio Battaglia Parodi, Peter R Pavan, James Peace, Don J Perez-Ortiz, Ayala Pollack, Kim Ramaswamy, Ramakrishna Ratnakaram, Giuseppe Ravalico, Jiri Rehak, Kourous Rezaei, Stanislao Rizzo, Francisco J Rodriguez-Alvira, Jean-Paul Romanet, Steven Rose, Richard B Rosen, Luca Rossetti, Jose Maria Ruiz-Moreno, SriniVas Sadda, Kenneth Sall, Dirk Sandner, Alvaro Fernandez-Vega Sanz, Gil Sartani, Stefanie Schmickler, Steven D Schwartz, Y R Sharma, Shwu-Jiuan Sheu, Michael Singer, Sobha Sivaprasad, Gisele Soubrane, Petr Soucek, Eric H Souied, Giovanni Staurenghi, Jan Studnicka, Marta Suarez-Figueroa, Walter Y Takahashi, Daniele Tognetto, Patrick L Tsai, Lawrence J Ulanski 2nd, Harvey Uy, Monica Varano, Miroslav Veith, Igor Vicha, Francesco Viola, Linda Visser, Dov Weinberger, Glenn L Wing, Edmund Wong, Tien Wong, Edward Wylegala, Jiong Yan, Young Hee Yoon, Lucy H Young, Hyeong G Yu, Ingrid E Zimmer-Galler
Abstract
Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).
Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.
Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.
Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.
Main outcome measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).
Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.
Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.
Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Source: PubMed