Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease

Joshua J. Field, Elaine Majerus, Victor R. Gordeuk, Michel Gowhari, Carolyn Hoppe, Matthew M. Heeney, Maureen Achebe, Alex George, Hillary Chu, Brian Sheehan, Maneka Puligandla, Donna Neuberg, Gene Lin, Joel Linden, David G. Nathan

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34 Scopus citations


Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A2AR agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A2AR agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A2AR agonist regadenoson (1.44 mg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of;5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a .30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of .30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P 5 .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.

Original languageEnglish
Pages (from-to)1645-1649
Number of pages5
JournalBlood Advances
Issue number20
StatePublished - Sep 12 2017


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