Drugs for preventing red blood cell dehydration in people with sickle cell disease

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#acetamides #anemia-sickle-cell #antisickling-agents #dehydration #erythrocyte-aging

Drugs for preventing red blood cell dehydration in people with sickle cell disease

Nagalla et al., 2010 | Cochrane Database Syst Rev | Meta Analysis

Citation

Nagalla Srikanth, Ballas Samir K. Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2010-Jan-20(1):CD003426. doi:10.1002/14651858.CD003426.pub3

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. OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 22 May 2009. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS: Of the 47 studies identified, two 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 (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 had to be stopped prematurely due to lack of reduction in the number of painful crisis. AUTHORS' CONCLUSIONS: While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicentre studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.Though the phase II study of senicapoc showed that the drug improved red cell survival, depending on dose, this did not lead to fewer painful crises; a subsequent phase III study was terminated prematurely for this reason.

Key Findings

Of the 47 studies identified, two 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 not

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 145
Age Range See abstract
Condition See abstract

MeSH Terms

  • Acetamides
  • Anemia, Sickle Cell
  • Antisickling Agents
  • Dehydration
  • Erythrocyte Aging
  • Erythrocytes
  • Humans
  • Randomized Controlled Trials as Topic
  • Triphenylmethyl Compounds
  • Zinc Sulfate

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: zinc

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09