Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: A phase III randomized, placebo-controlled, double-blind study of the gardos channel blocker senicapoc (ICA-17043)

Kenneth I. Ataga, Marvin Reid, Samir K. Ballas, Zahida Yasin, Carolyn Bigelow, Luther St James, Wally R. Smith, Frederic Galacteros, Abdullah Kutlar, James H. Hull, Jonathan W. Stocker

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Red blood cell (RBC) hydration is regulated in part by the Ca2+-activated K+ efflux (Gardos) channel. Senicapoc selectively blocks potassium efflux through the Gardos channel, reducing RBC dehydration and haemolysis, and increasing haemoglobin levels in sickle cell disease (SCD). This randomized, placebo-controlled trial was designed to determine the safety and clinical efficacy of senicapoc in SCD patients. One hundred and forty-five patients were randomized to receive senicapoc and 144 patients to receive placebo for 52weeks. Consistent with a previous study, patients in the senicapoc group had significantly increased haematocrit, haemoglobin, and decreased numbers of both dense erythrocytes and reticulocytes when compared to the placebo group. The unblinded Data Monitoring Committee terminated this study early due to a lack of efficacy when it determined that, despite improvements in anaemia and haemolysis, no significant improvement in the rate of sickle cell painful crises was observed in patients treated with senicapoc compared to those on placebo (0·38 vs. 0·31, respectively). Comparisons of the times to first, second and third crises between the senicapoc and placebo groups were not statistically significant. Nausea and urinary tract infections occurred more frequently in the senicapoc group than placebo. Serious adverse events were similar in the two groups.

Original languageEnglish (US)
Pages (from-to)92-104
Number of pages13
JournalBritish Journal of Haematology
Volume153
Issue number1
DOIs
StatePublished - Apr 1 2011

Keywords

  • Gardos channel
  • KCa3·1
  • Red blood cell
  • Senicapoc
  • Sickle cell disease

ASJC Scopus subject areas

  • Hematology

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