Pooled Efficacy Results From Two Multinational Randomized Controlled Clinical Trials of a Single Intravitreous Injection of Highly Purified Ovine Hyaluronidase (Vitrase ®) for the Management of Vitreous Hemorrhage

• Published in: American journal of ophthalmology 2005-10, Vol.140 (4), p.573-584
• Main Authors: Kuppermann, Baruch D., Thomas, Edgar L., de Smet, Marc D., Grillone, Lisa R.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood; Clinical trials; Diabetes; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 2 - complications; Diabetic retinopathy; Double-Blind Method; Female; Humans; Hyaluronoglucosaminidase - administration & dosage; Injections; Male; Medical sciences; Middle Aged; Miscellaneous; Ophthalmology; Pathology; Prospective Studies; Quality of life; Retina; Studies; Treatment Outcome; Visual Acuity - physiology; Vitreous Body - drug effects; Vitreous Hemorrhage - drug therapy; Vitreous Hemorrhage - physiopathology
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2005.04.018

To evaluate the efficacy of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. Two prospective, randomized, placebo-controlled, double-masked studies. Safety data are presented in a companion article in the journal. Eligible patients with vitreous hemorrhage ≥1 month duration; severe at entry with best corrected visual acuity (BCVA) worse than 20/200 were randomized to 55 IU or 75 IU ovine hyaluronidase or saline. Primary efficacy (clearance of hemorrhage sufficient to see the underlying pathology and completion of treatment when indicated) was measured at months 1, 2, and 3. Key secondary endpoints were: ≥3-line improvement in BCVA; hemorrhage density reduction; and therapeutic utility assessment. The intent-to-treat population for common dose groups (55 IU, 75 IU, saline) consisted of 1125 patients. At baseline, 76.3% had diabetes, 90.4% were not able to read any letters on the eye chart, and mean hemorrhage duration was 120 days. Statistical significance was reached in the 55 IU dose group by months 1 and 2 for the primary efficacy endpoint based on an adjusted P-value. By months 1, 2, and 3, 13.2%, 25.5%, and 32.9% of patients (55 IU) reached primary efficacy compared with 5.5%, 16.2%, and 25.6% of saline-treated patients ( P < .001; P = .002; P = .025, respectively). Key secondary endpoints confirmed the treatment effect at both doses and all timepoints ( P ≤ .01). Fifty-five IU ovine hyaluronidase showed statistically significant efficacy as early as months 1 and 2. These results were supported by outcomes for three key secondary endpoints. These results suggest a therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage.