Evidence Table 1. Description of Randomized Controlled Trials Investigating the Efficacy of Hydroxyurea Treatment for Sickle Cell Disease

Author, yearLocationDesignRecruitment start date - end dateInclusion and exclusion criteriaInterventionStarting dose: titration dosePlanned duration of treatmentJadad 29 score
Charache, 199521North AmericaRCTJan 1992 – Apr 1993Inclusion: Age >18; SCA; Hb Sα+ thal, Pain >3/yr2 years5
Charache, 199639Exclusion: Hb Sβ+ thal; β0 thal; SC; xfuse dependant; Preg; Op; SA; CTA; stroke in last 6 years; HIV; HU; not willing to use contraception; blood counts that could not be distinguished from marrow suppression; >15% HbA if recent transfusion; breastfeeding2 years4
Hackney, 19974118 months3
Steinberg, 1997402 years4
Moore, 2000 222 years4*
Steinberg, 200343Cohort (f/u of MSH)
Ballas, 200642RCTHU 15 mg/kg/day: increased 5 mg/kg every 12 weeks if ANC ≥2000, retic and platelets ≥80,000/ul, and Hb ≥4.5 g/dl 2 years 4
PlaceboEscalation per Data Coordinating Center (random)
Pediatric-Belgian Trial
Ferster, 199844EuropeCross-overJune 1992 – Dec 1993Inclusion: SCA, Hb Sα+ thal; 3/yr pain episodes, stroke; acute chest; splenic sequestrationHU 20mg/kg/day: increased by 5mg/kg/day after 2 months, if no response increased to 25 mg/kg 6 months 3
Exclusion: Hb Sβ+ thal; Hb S β0 thalPlaceboNot described6 months

Quality Deficiency: No description of withdrawals or dropouts.

Observational Study


ANC = absolute neutrophil count; CTA = concurrent treatment with an anti-sickling agent; f/u = follow up; Hb Sβ thal = sickle β thalassemia; Hb S β0 thal = Sickle β0 thalassemia; Hb Sα thal = Sickle α thalassemia; HbA = hemoglobin A; HIV = Human Immunodeficiency Virus; HU = hydroxyurea; MSH = Multicenter Study of Hydroxyurea for Sickle Cell Anemia; Op = opioid use; Pain = pain episode; Preg = pregnancy; RCT = Randomized controlled trial; retic = reticulocytes; SA = substance abuse; SC = SC genotype; SCA = sickle cell anemia; xfuse = transfusion dependant.

From: Appendix C: Evidence Tables

Cover of Hydroxyurea for the Treatment of Sickle Cell Disease
Hydroxyurea for the Treatment of Sickle Cell Disease.
Evidence Reports/Technology Assessments, No. 165.
Segal JB, Strouse JJ, Beach MC, et al.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.