Effects on general safety and coagulation after long-term, high-dose volume therapy with 6% hydroxyethyl starch 130/0.4 in patients with acute ischemic stroke. Results of a randomized, placebo-controlled, double-blind study

Introduction

In the past, high-molecular weight, highly substituted hydroxyethyl starch (HES) 450/0.7, which is mostly used in the United States, has been implicated in bleeding complications, some of them lethal. In Europe, medium-molecular weight HES with a low degree of substitution (0.5) has been preferred. The present study investigated, whether a long-term, high-dose volume therapy with a newly developed 6% HES 130/0.4 (Voluven^®) is safe in patients suffering from acute ischemic stroke. In particular, the effects on hemostaseology were examined.

Patients and methods

In a randomized, double-blind, placebo-controlled study carried out in accordance with GCP and ICH guidelines, 40 patients suffering from acute ischemic stroke received either 6% HES 130/0.4 or crystalloid solution, after giving their informed consent. There were no differences between the treatment groups regarding demography and baseline characteristics. Each patient received a loading dose of 500 ml HES or crystalloid solution over 1 hour and subsequently 1500 ml HES or crystalloid solution per day over a period of 4 days for a total dose of 6500 ml. Hemostaseological parameters (platelets, prothrombin time, aPTT, fibronectin, Factor VIII:C, von Willebrand factor antigen, von Willebrand Ristocetin cofactor) were measured daily. Patients were followed-up until 90 days post treatment.

Results

A total of 390 g HES per patient was administered and well tolerated by all patients in the study group. Only one serious adverse event was noted in the crystalloid group, whereby a relation with the study medication was unlikely. The most frequent adverse event was itching, reported by two patients in the crystalloid group and three patients in the HES group.

At baseline all hemostatic parameters were within the normal range and no clinically relevant changes were observed with respect to any parameter between the two treatment groups.

Conclusions

Medium molecular weight HES 130 with a low degree of substitution (0.4) was well tolerated and can be administered in larger doses over longer periods of time without relevant effects on hemostaseology compared to a crystalloid group. In particular, there is no increased risk of bleeding in this clinical setting.