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Br J Haematol. 2011 Apr;153(1):92-104. doi: 10.1111/j.1365-2141.2010.08520.x. Epub 2011 Feb 17.

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).

Collaborators (364)

Abdul-Rachid N, Bernstein J, Kline R, Bayreder A, Buitrago J, Adams-Graves P, Dugdale M, Ataga K, Orringer EP, Jones SK, Strayhorn DH, Asogbade M, Thein SL, Ballas S, McRay M, Lusardi M, Barbosa J, Grana N, Lukas C, Ayala I, Vrchoticky T, Kerr K, Aung L, Bellevue R, D'Augustine J, Nejamin L, Swinson GI, McMillion B, Bessman J, Whitehead RP, Suleman K, Willis M, Valencia-Stephens L, Crawford P, Hirsch SJ, Bigelow C, Herrin V, Hamilton RD, Blinder M, Field J, Carlos T, Redner R, Charles K, Seemungal TA, Leelah N, Ajayi TA, CHingos J, Pham DC, Walker RA, Rana FN, Mignone J, Villegas AE, Cohen A, Sha M, Rogers-Phillips E, Sabnani I, Cruz J, Leedy D, O'Brien F, MacLean J, Daeschner C, Grossi M, Dampier C, Luck L, Mba N, Meier M, Rockstein M, Cahill M, Moore A, DeCastro L, Jonassaint JC, Zimmerman S, Greenberg C, Friedman D, Laubach J, Whitlatch N, Pawloski JR, Anders C, Lanasa M, Palmer J, Zafar Y, Haith K, Figueiredo MS, Neto FM, Cavalheiro Rde C, Vicari P, Flug F, Appel B, Diamond S, Gregory J, Halpern S, Harlow P, Harris MB, Steele CS, Terrin B, Galacteros F, Anoosha H, Marie-Odette B, Dora B, Godder K, Gullquist S, Dunn NL, Massey GV, Laver J, Khan A, Hall E, Mauck A, Shockey D, Casper R, Temple B, Russell EC, Brunner T, Greist A, Shapiro A, Riley R, Hummel K, Muhammad A, Miller-Rice L, Parameswaran R, Guillaume E, Jaffe E, Wilson C, Hagar W, Stewart K, Hoehner C, Edwards S, Styles LA, Hagston N, Parikh N, Altman A, Gillan E, Steven K, Peluso E, Harrison J, Saidi P, Philipp C, Rose S, Michaels L, Drachtman R, Hassel K, Nuss R, Haynes J, Pack-Mabien A, Hussein A, Bronte L, Cohen J, Restrepo M, Bankston S, Glasser R, Lewis MS, Cano R, Franco S, Grosman D, Abraham A, Domenech G, Perez AT, Jackson S, Cavalier ME, Disco D, Peterson J, Rackoff E, Bergman S, Johnson S, Debenham E, Jeroudi K, Springer MA, Todd L, Bass PF 3rd, Joiner C, Balsa V, Kalinyak K, Gruppo R, Malik P, Palumbo J, Kalfa T, Lagory D, Nordheim T, Johnson V, Terry A, Wilson D, Hodgson M, Boyd P, Hackworth L, Kelly P, Smith F, Norman A, Godfrey D, Chan E, Juneja H, Ellent D, Brown D, Wu KK, Ghelani D, Kassim A, Winslow L, Nilson D, Klintworth S, Knupp C, Liles D, Krishnamurti L, Gunawardena SW, Windsor BA, Sakara AA, Lindsey CL, Kutlar A, Wells L, Daitch L, McKie K, McKie V, Natarajan K, Lanzkron S, David M, Roane Y, Lobo CL, Moura PG, Cerqueira Eda C, Queiroz AM, Queiroz AP, Loew T, DiPaola J, Goldman F, O'Dorisio MS, Radhi M, Tannous R, Vibhakar R, Hohl R, Holida M, McMillan S, McCaffrey R, Churchil WH, Okam MM, Mandell E, Souza M, Connors JM, Miller S, Rey K, Rao SP, Moore R, Langevin AM, Carpenter S, Britton H, Shah S, Mueller B, Mahoney DH, McClain K, Airewele G, Bryant R, Onyekwere O, DeGannes C, Castro O, Pefkarou A, Escalon EA, Warman R, Khatib ZA, Fort JA, Reid M, Cunningham-Myrie CA, Cumming V, Parshad-Asnani M, Knight-Madden J, Madden W, Lewis N, Saccente S, Becton D, Stein KC, Saylors RL, Samaik S, Whitten-Shurney WJ, Chitlur M, Strother K, Henderson OG, Saunthararajah Y, Labotka R, Molokie R, Saraf S, Sidhwani S, Gowhari M, Scher C, Kahn MJ, Hemenway CS, Rozans MK, Schorin MA, Schilelr G, Territo MC, Paquette R, Mariano da Rocha Silla L, Fogliatto LM, Friedrisch JR, Lehugteur DS, Smith W, Aiusiku I, White L, Smith-Whitley K, Kwiatkowski J, Ohene-Frempong K, Solomon W, Gillette P, Egan S, Kamenova B, St James L 3rd, Tanner-St James C, Blair-Britt L, Nesbitt CC, Iskander RS, Mather N, Styles L, Stewart K, Truskier MG, Edwards S, Hagar RW, Subramanian-Srinivsan U, Swerdlow P, Ortega J, Littsey L, Jett AR, Tebbi C, Wynn T, Obzut D, Rossbach HC, Telfer P, Kaya B, Uddon M, Vats T, Gonzales CE, Frankel LS, Villella A, Blumer JL, Berman BW, Gibbons J, Lemon E, Viswanathan K, Boruchov D, Khalil M, Kalavar MR, Naik S, Dumlao TL, Arora A, Warrier R, Gardner R, Yu L, Velez M, Singleton T, Wolff S, Posey L, Woods G, Neville K, Sarcone S, Stegenga K, Routhieaux J, Roath G, Wright L, Bhatia S, Wun T, Yasin Z, Pruemer J, Palascak J, Gupta A, Pancoast J, Naheleh Z, Jazieh AR, Zakarija A, Green D, Herman C, Soff G.

Author information

1
University of North Carolina, Chapel Hill, NC, USA.

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.

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