Rutgeerts et al published the fourth study, a very large (854-patient) multicentre randomized trial that included three groups: polidocanol; fibrin glue; and daily fibrin glue injections until high risk stigmata disappeared. Recurrent bleeding occurred in 19% of the 266 patients in the fibrin glue arm and 15% of the 270 patients randomized to repeated fibrin glue injections. There were no significant differences in rates of rebleeding, surgery or death.
Apart from a negative trial published in abstract form by Ell , the latest randomized study was published by Messmann et al in 1998. After initial treatment with epinephrine and fibrin or thrombin, 105 patients were randomized to either programmed endoscopic monitoring (second look) at 16 h to 24 h or conservative therapy, where a second endoscopy was performed only if there were clinical signs of rebleeding. Only 19% of the programmed endoscopy subjects had persistent high risk stigmata that were worth treating. There were no differences in clinical outcomes such as transfusion requirements or rates of rebleeding (21% versus 17%), surgery or mortality. Fourteen patients in the second look group rebled and, similar to the Villanueva et al study , 29% did so before the second endoscopy. One-half of the rebleeding episodes occurred despite a second course of endoscopic therapy and 21% of them were actually in patients considered to be at low risk at their second endoscopy. This finding again illustrates the potential danger of using the Forrest classification outside the context of the initial (pretreatment) endoscopic assessment. Early discharge or early discontinuation of intravenous proton pump inhibitors would have been detrimental to these patients.