This clinical trial was terminated early because of slow accrual. Episodes of ACS that met our stringent definition occurred less frequently than we anticipated, especially because we excluded mild and rapidly resolving ACS episodes that frequently occur in young children. Moreover, the unpredictable presentation of acutely ill, potential study participants was a great logistical challenge for study sites.
Even in this small sample, dexamethasone appeared to shorten duration of hospitalization by 20 h, consistent with prior studies and suggesting a large treatment effect size of corticosteroids in SCD (Bernini, et al 1998
, Griffin, et al 1994
). No other benefits were obvious, although the direction of treatment effects favoured dexamethasone in all efficacy outcomes (). Rebound pain occurred in both groups, with numerically more rebound pain episodes with dexamethasone (P=0.24). A larger, significant difference may have emerged in the much larger intended sample size. Simply adding a taper may not have been sufficient to prevent rebound toxicity, but the magnitude of benefit of the taper, if any, cannot be determined from this study. Finally, although we attempted to standardize supportive care for all participants, differences in supportive care between treatment groups might have accounted for some of the observed treatment effect or adverse effects, especially in the small sample.
The leucocyte activation marker, sL-selectin, decreased with dexamethasone. Given that activated leucocytes contribute to vaso-occlusion (Okpala 2004
), this might represent a laboratory correlate of response to corticosteroids for ACS and pain (Bernini, et al 1998
, Griffin, et al 1994
). Patients who had rebound pain (dexamethasone or placebo group) had higher sL-selectin after 24 h of study-drug, further suggesting that suppression of leucocyte activation might prevent rebound pain and ameliorate ACS. Dexamethasone also decreased levels of nitric oxide metabolites, probably explained by suppression of inducible nitric oxide synthase (Walker, et al 1997
). As such, dexamethasone has several different effects that individually may or may not be beneficial for ACS.
Randomized, controlled acute intervention studies are lacking but critically needed for patients with SCD. Most of the care for ACS, and other acute vaso-occlusive complications, is based on anecdotal and uncontrolled clinical evidence. A multi-centre, randomized trial of tapered dexamethasone is feasible but, based on our study, may require as many as 25 clinical sites and 5 years of patient accrual. We conclude that our novel ACS assessment tool was feasible to apply and should be further studied to establish its construct validity, and that sL-selectin is a promising biomarker of ACS therapy. Future acute intervention studies for ACS should incorporate objective assessment tools and biomarkers of therapy.