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

Peter Olupot-Olupot, Charles Engoru, Jennifer Thompson, Julius Nteziyaremye, Martin Chebet, Tonny Ssenyondo, Cornelius M Dambisya, Vicent Okuuny, Ronald Wokulira, Denis Amorut, Paul Ongodia, Ayub Mpoya, Thomas N Williams, Sophie Uyoga, Alex Macharia, Diana M Gibb, A Sarah Walker, Kathryn Maitland, Peter Olupot-Olupot, Charles Engoru, Jennifer Thompson, Julius Nteziyaremye, Martin Chebet, Tonny Ssenyondo, Cornelius M Dambisya, Vicent Okuuny, Ronald Wokulira, Denis Amorut, Paul Ongodia, Ayub Mpoya, Thomas N Williams, Sophie Uyoga, Alex Macharia, Diana M Gibb, A Sarah Walker, Kathryn Maitland

Abstract

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.

Trial registration: ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.

Figures

Figure 1
Figure 1
Trial flow.
Figure 2
Figure 2
Correction of severe anemia by 24 hours by study arm. Time to first hemoglobin>6mg/dl by study arm by study arm (primary outcome- correction of severe anemia).
Figure 3
Figure 3
Change in mean hemoglobin (3a) and lactate (3b) over follow up by study arm. a. Hemoglobin over 28 days. b. Lactate levels over 24 hours.

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