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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).
Br J Haematol 2011; 153(1):92-104BJ

Abstract

Red blood cell (RBC) hydration is regulated in part by the Ca(2+) -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 52 weeks. 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.

Authors+Show Affiliations

University of North Carolina, Chapel Hill, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21323872

Citation

Ataga, Kenneth I., et al. "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)." British Journal of Haematology, vol. 153, no. 1, 2011, pp. 92-104.
Ataga KI, Reid M, Ballas SK, et al. 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). Br J Haematol. 2011;153(1):92-104.
Ataga, K. I., Reid, M., Ballas, S. K., Yasin, Z., Bigelow, C., James, L. S., ... Stocker, J. W. (2011). 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). British Journal of Haematology, 153(1), pp. 92-104. doi:10.1111/j.1365-2141.2010.08520.x.
Ataga KI, et al. 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). Br J Haematol. 2011;153(1):92-104. PubMed PMID: 21323872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). AU - Ataga,Kenneth I, AU - Reid,Marvin, AU - Ballas,Samir K, AU - Yasin,Zahida, AU - Bigelow,Carolyn, AU - James,Luther St, AU - Smith,Wally R, AU - Galacteros,Frederic, AU - Kutlar,Abdullah, AU - Hull,James H, AU - Stocker,Jonathan W, AU - ,, Y1 - 2011/02/17/ PY - 2011/2/18/entrez PY - 2011/2/18/pubmed PY - 2011/5/7/medline SP - 92 EP - 104 JF - British journal of haematology JO - Br. J. Haematol. VL - 153 IS - 1 N2 - Red blood cell (RBC) hydration is regulated in part by the Ca(2+) -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 52 weeks. 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. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/21323872/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__ L2 - https://doi.org/10.1111/j.1365-2141.2010.08520.x DB - PRIME DP - Unbound Medicine ER -