title: Drugs for preventing red blood cell dehydration in people with sickle cell disease.
abstract: BACKGROUND
  Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review.
  
  
  OBJECTIVE
  To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.
  
  
  METHODS
  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015.
  
  
  METHODS
  Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment.
  
  
  METHODS
  Both authors independently selected studies for inclusion, assessed study quality and extracted data.
  
  
  RESULTS
  Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises.
  
  
  CONCLUSIONS
  While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.
authors.affiliation: Department of Medicine, Division of Hematology, Thomas Jefferson University, Medical Center Boulevard, 1015 Walnut Street, Philadelphia, Pennsylvania, USA, PA 19107-5099.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Nagalla
authors.forename: Samir K
authors.initials: SK
authors.lastname: Ballas
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000755:Anemia, Sickle Cell / Q000097:blood*; D000986:Antisickling Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003681:Dehydration / Q000517:prevention & control*; D057239:Early Termination of Clinical Trials; D004905:Erythrocyte Aging / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D006801:Humans; D010889:Piracetam / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014320:Triphenylmethyl Compounds / Q000627:therapeutic use*; D019287:Zinc Sulfate / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000986:Antisickling Agents; D014320:Triphenylmethyl Compounds; D019287:Zinc Sulfate; C472774:senicapoc; D010889:Piracetam