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Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Cochrane Database Syst Rev 2010; (1):CD003426CD

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.

Authors+Show Affiliations

Division of Hematology & Oncology, Thomas Jefferson University, 1015 Walnut Street, 705 Curtis Building, Philadelphia, USA, PA 19107.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

20091545

Citation

Nagalla, Srikanth, and Samir K. Ballas. "Drugs for Preventing Red Blood Cell Dehydration in People With Sickle Cell Disease." The Cochrane Database of Systematic Reviews, 2010, p. CD003426.
Nagalla S, Ballas SK. Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2010.
Nagalla, S., & Ballas, S. K. (2010). Drugs for preventing red blood cell dehydration in people with sickle cell disease. The Cochrane Database of Systematic Reviews, (1), p. CD003426. doi:10.1002/14651858.CD003426.pub3.
Nagalla S, Ballas SK. Drugs for Preventing Red Blood Cell Dehydration in People With Sickle Cell Disease. Cochrane Database Syst Rev. 2010 Jan 20;(1)CD003426. PubMed PMID: 20091545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drugs for preventing red blood cell dehydration in people with sickle cell disease. AU - Nagalla,Srikanth, AU - Ballas,Samir K, Y1 - 2010/01/20/ PY - 2010/1/22/entrez PY - 2010/1/22/pubmed PY - 2010/4/17/medline SP - CD003426 EP - CD003426 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 1 N2 - 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/20091545/Drugs_for_preventing_red_blood_cell_dehydration_in_people_with_sickle_cell_disease_ L2 - https://doi.org/10.1002/14651858.CD003426.pub3 DB - PRIME DP - Unbound Medicine ER -