Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia

BMC Medicine

Kathryn Maitland⁴  A Sarah Walker³  Diana M Gibb³  Alex Macharia²  Sophie Uyoga²  Thomas N Williams⁴  Ayub Mpoya²  Paul Ongodia¹  Denis Amorut⁵  Ronald Wokulira⁵  Vicent Okuuny⁵  Cornelius M Dambisya¹  Tonny Ssenyondo¹  Martin Chebet¹  Julius Nteziyaremye³  Jennifer Thompson³  Charles Engoru⁵  Peter Olupot-Olupot¹ 

[1] Department of Paediatrics, Mbale Regional Referral Hospital, Pallisa Road Zone, PO Box 921, Mbale, Uganda;Kilifi Clinical Trials Facility, KEMRI-Wellcome Trust Research Programme, PO Box 230, Kilifi, Kenya;Medical Research Council (MRC) Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, UK;Wellcome Trust Centre for Clinical Tropical Medicine, Department of Paediatrics, Faculty of Medicine, St Marys Campus, Norfolk Place, Imperial College, London W2 1PG, UK;Department of Paediatrics, Soroti Regional Referral Hospital, PO Box 289, Soroti, Uganda

关键词: Infectious disease;    Clinical trial;    African children;    Severe anemia;    Transfusion;   

Others  :  854908
DOI  :  10.1186/1741-7015-12-67

 received in 2013-12-20, accepted in 2014-03-17,  发布年份 2014

【 摘 要 】

Background

Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes.

Methods

We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range (IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival.

Results

Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload.

Conclusion

A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted.

Please see related commentary article http://www.biomedcentral.com/1741-7015/12/68/abstract webcite.

Trial registration

ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.

【 授权许可】

   
2014 Olupot-Olupot et al.; licensee BioMed Central Ltd.

【 图 表 】

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