a-t 2016; 47: 109

Hydroxyethyl starch (HES; e.g. VOLUVEN) - requested trials have not even started: Due to an increased risk of kidney damage and an increase in mortality in several studies, hydroxyethyl starch (HES; e.g. VOLUVEN; a-t 2013; 44: 30) has been contraindicated in critically ill people and patients with sepsis or burns since 2013. Since then infusion solutions containing HES have only been authorised for hypovolaemia due to acute blood loss if crystalloid solutions alone are not sufficient (1). For this niche indication, the European Medicines Agency (EMA) requested that HES providers carry out large, randomised studies (a-t 2013; 44: 113) focusing on renal toxicity and mortality. These were ordered by the Federal Institute for Drugs and Medical Devices (BfArM) in early 2014. Trial protocols should have been submitted within six months after the implementing decision and final study reports by the end of 2016 (2). However, the relevant studies have not even begun. Two studies sponsored by the providers B. Braun Melsungen and Fresenius Kabi (3, 4) are only scheduled to start in early 2017 and then be completed within two years (5, 6). Serumwerk Bernburg, the third remaining HES provider in Germany,* is not involved in the studies and is also not planning its own (7, 8). BfArM has tried multiple times in the meantime to order the temporary suspension of the authorisation for HES products by this provider, but has not yet been successful in this endeavour before the court (7-9). We advise against the use of HES even within the remaining indication and continue to support market withdrawal, -Ed.

  1 EMA: press release, 19 Dec. 2013; http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Solutions_for_infusion_ containing_hydroxyethyl_starch/European_Commission_final_decision/WC500162361.pdf
  2 BfArM: notice on graduated plan, 5 Febr. 2014; http://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Pharmakovigilanz/Risikoinformationen/ RisikoBewVerf/g-l/hes-bescheid.pdf?__blob=publicationFile&v=2
  3 European Society of Anaesthesiology: Flyer "PHOENICS - Perioperative HES Trial", 23 Aug. 2016; https://www.esahq.org/~/media/ESA/Files/ClinicalTrialNetwork/CRO/HES%20PHOENICS%20Flyer%20v21%2023AUG16.ashx
  4 European Society of Anaesthesiology: Flyer "TETHYS - Trauma HES Trial", 23 Aug. 2016; https://www.esahq.org/~/media/ESA/Files/ClinicalTrialNetwork/CRO/HES%20TETHYS%20%20Flyer%20v21%2023AUG16.ashx
  5 BfArM: letter dated 21 Oct. 2016
  6 Fresenius Kabi: letter dated 28 Oct. 2016
  7 BfArM: notice on suspending the marketing authorisation dated 30 Sept. 2015; http://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Pharmakovigilanz/ Risikoinformationen/RisikoBewVerf/g-l/hes-ruhensbescheid-20150930.pdf?__blob=publicationFile&v=3
  8 BfArM: notice on suspending the marketing authorisation dated 12 Oct. 2016; http://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Pharmakovigilanz/ Risikoinformationen/RisikoBewVerf/g-l/hes-ruhensbescheid-20161012.pdf?__blob=publicationFile&v=2
  9 Serumwerk Bernburg: letter dated 1 Nov. 2016

  * To the best of our knowledge Baxter has no longer been supplying HES solutions since 2013.

  Caution: less than five years on the market or under additional monitoring according to the European Medicines Agency

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