Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial.

PURPOSE: The reported outcomes of central retinal artery occlusion (CRAO) with or without treatment vary considerably. Although local intra-arterial fibrinolysis (LIF) using recombinant tissue plasminogen activator (rtPA) is a promising treatment, outcomes have not been compared in randomized trials. DESIGN: Prospective randomized multicenter clinical trial (the European Assessment Group for Lysis in the Eye Study) to compare treatment outcome after conservative standard treatment (CST) and LIF for acute nonarteritic CRAO. PARTICIPANTS: Between 2002 and 2007, 9 centers in Austria and Germany recruited 84 patients (40 received CST, 44 received LIF), and data for 82 patients were analyzed. METHODS: Patients (age 18-75 years) with CRAO, symptoms for 20 hours or less, and best-corrected visual acuity (BCVA) <0.5 logarithm of the minimum angle of resolution (logMAR) were randomized to the CST or LIF group. MAIN OUTCOME MEASURES: The primary end point was BCVA after 1 month; the secondary end point was safety. RESULTS: The mean interval between first symptoms and therapy was 10.99+/-5.49 hours (CST) and 12.78+/-5.77 hours (LIF). The mean BCVA (logMAR) improved significantly in both groups (CST: -0.44 [standard deviation 0.55]; LIF: -0.45 [standard deviation 0.55]; both P < 0.0001) and did not differ between groups (P=0.69). Clinically significant visual improvement (> or = 0.3 logMAR) was noted in 60.0% (CST) and 57.1% (LIF) of patients. Two patients in the CST group (4.3%) and 13 patients in the LIF group (37.1%) had adverse reactions. Because of apparently similar efficacy and the higher rate of adverse reactions in the LIF group, the study was stopped after the first interim analysis at the recommendation of the data and safety monitoring committee. CONCLUSIONS: In light of these 2 therapies' similar outcomes and the higher rate of adverse reactions associated with LIF, we cannot recommend LIF for the management of acute CRAO. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Good clinical practice: historical background and key aspects.

Clinical research trials (both academic and industry sponsored) are increasingly playing a role in various medical disciplines, including younger fields of clinical trial interest, such as nuclear medicine research. Knowledge for and compliance with good clinical practice (GCP) is essential for anyone involved. In this review article, key aspects of GCP and the responsibilities of investigators, monitors and sponsors are described. In addition, a comprehensive overview of the historical background on the development of GCP from the US Pure Food and Drugs Act of 1906 over the Nuremberg Code, the Kefauver-Harris Amendments and the Declaration of Helsinki until now is given. Knowledge of the historical background may help understand the developments in GCP.