Tags

Type your tag names separated by a space and hit enter

Drugs for preventing red blood cell dehydration in people with sickle cell disease.
Cochrane Database Syst Rev 2012; (7):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 METHODS

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 25 October 2011.

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 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.

AUTHORS' 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.

Authors+Show Affiliations

Department of Medicine, Division of Hematology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

22786485

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, 2012, p. CD003426.
Nagalla S, Ballas SK. Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2012.
Nagalla, S., & Ballas, S. K. (2012). Drugs for preventing red blood cell dehydration in people with sickle cell disease. The Cochrane Database of Systematic Reviews, (7), p. CD003426. doi:10.1002/14651858.CD003426.pub4.
Nagalla S, Ballas SK. Drugs for Preventing Red Blood Cell Dehydration in People With Sickle Cell Disease. Cochrane Database Syst Rev. 2012 Jul 11;(7)CD003426. PubMed PMID: 22786485.
* 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 - 2012/07/11/ PY - 2012/7/13/entrez PY - 2012/7/13/pubmed PY - 2012/9/22/medline SP - CD003426 EP - CD003426 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 7 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 METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 25 October 2011. 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 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. AUTHORS' 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/22786485/Drugs_for_preventing_red_blood_cell_dehydration_in_people_with_sickle_cell_disease_ L2 - https://doi.org/10.1002/14651858.CD003426.pub4 DB - PRIME DP - Unbound Medicine ER -