Poloxamer 188 – helpful during a painful crisis or not?

Research involving Poloxamer 188 (also know as RheothRx or MST 188) continues to appear in the journals. The latest is some interesting work from a team working in Hungary and France published in the British Journal of Haematology (1).

Poloxamer 188 is an intravenous preparation which improves the flow properties of the blood and which was hoped would shorten or terminate a painful vaso-occlusive crisis, see previous blog from 03/06/14 “Update on clinical trials in sickle cell disease”. It’s initial use in sickle cell was reported 19 years ago in 1997, when indeed the results were very encouraging (2). But a follow up study in 2001, by the same group of doctors from the University of Tennessee, with a larger group of patients, did not show such positive results (3). Nevertheless, there was still some reduction in the length of a painful crisis and the time spent in hospital, particularly noticeable in children. A further study in 2004, this time restricted to patients admitted with the acute chest syndrome, failed to show any positive benefit on outcome (4).

Despite these disappointing clinical results, experimental work in the laboratory continues to suggest that poloxamer 188 may be a useful therapeutic option in sickle cell. The latest research (1) looked at blood collected from patients with sickle cell anaemia and assessed its “flow” and “adhesive” properties using a variety of tests, both with and without pre-exposure of the red cells to poloxamer 188. The investigators found that pre-exposure to poloxamer 188 reduced the viscosity or “thickness” of the blood, reduced the tendency of the sickle red cells to aggregate together and reduced the tendency of sickle red cells to stick to endothelial cells, which the lining of the inside of blood vessels. As the authors point out, all three of these properties would be expected to improve blood flow and therefore have a beneficial effect in a painful crisis, where the pain is thought to be caused by sickle cells obstructing blood flow and limiting oxygen supply to the tissues downstream.

Each poloxamer 188 molecule has one "sticky" part (in white) and two "slippery" parts (in blue). The sticky part fastens to damaged areas of the red cell membrane leaving the slippery parts to encourage red cells to flow more easily past each other and along the inside lining of the blood vessels.

Each poloxamer 188 molecule has one “sticky” part (in white) and two “slippery” parts (in blue). The sticky part fastens to damaged areas of the red cell membrane leaving the slippery parts to encourage red cells to flow more easily past each other and along the inside lining of the blood vessels.

The contrast between the marked effects found in the test tube and the limited benefits found in the clinical studies may be because by the time the pain begins to be felt the damage has already been done. The lack of oxygen downstream has already led to the death of tissues and cells and initiated an acute inflammatory reaction, which is the source of the pain. Improving blood flow at this point using poloxamer 188 would not necessarily have a major effect on the course on the crisis.

However, the question will only be resolved by a formal clinical trial with sufficient numbers of patients to give statistically significant results. Such a multi-centre trial, known as the EPIC trial (Evaluation of Purified poloxamer 188 or MST 188 In Crisis), was begun in May 2013 in hospitals across the USA. The trial is looking at children, aged 8-17 years, with sickle cell anaemia in crisis. The key factor will be whether treatment with poloxamer 188 shortens the duration of the crisis (time from admission to the time of the last dose of opiate painkiller) by 16 hours or more. The organisers of the trial thought they would need 388 patients to prove whether this is possible or not, and enrolment of sufficient numbers of patients was completed in February this year. Hopefully we will not have to wait much longer to know whether poloxamer 188 is of any practical use in sickle cell or not.

  1. Effects of poloxamer 188 on red blood cell membrane properties in sickle cell anaemia. Sandor B, Marin M, Lapoumeroulie C et al. British Journal of Haematology (2016), volume 173, pages 137-144.
  2. RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Adams-Graves P, Kedar A, Koshy M et al. Blood (1997), volume 90, pages 2041-2046.
  3. Purified poloxamer 188 for the treatment of the acute vaso-occlusive crisis of sickle cell disease. Orringer E, Casella J, Ataga K et al. Journal of the American Medical Association (2001), volume 286, pages 2099-2106.
  4. Safety of purified poloxamer 188 in sickle cell disease: phase 1 study of non-ionic surfactant in the management of the acute chest syndrome. Ballas S, Files B, Luchtman-Jones L et al. Hemoglobin (2004), volume 28, pages 85-102.
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About rogerjamos

I am a consultant haematologist who has worked in Hackney, London, UK with patients who have sickle cell disease for many years. Knowledge is power; the hope is that this blog will empower patients by putting them in touch with contemporary research into sickle cell disease and facilitating informed discussion on the issues raised. Dr Roger Amos MA, MD, FRCPath
This entry was posted in drug trials, pain, red cell adhesion, sickle cell disease and tagged , , , , . Bookmark the permalink.

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