One of the main problems in sickle cell disease is the decreased bioavailability of nitric oxide and arginine. This study was designed to assess if treating sickle cell disease patients with L-arginine would improve pulmonary arterial pressure and other aspects.

This is a phase III, randomized, double-blind, placebo-controlled clinical trial with sickle cell disease patients older than 1 year of age. The patients were randomly assigned to take 0.1 g/kg/day of either L-arginine or placebo orally. Adverse events were monitored by a safety committee. The variables were assessed while patients were in remission, as part of their routine care: weight, blood pressure, full blood cell count, creatinine and dosage of methemoglobin at baseline and at each follow-up visit. Peripheral oxygen saturation (SpO2), fetal hemoglobin, lactate dehydrogenase and tricuspid regurgitant jet velocity were measured through transthoracic Doppler echocardiogram before and after treatment.

Inclusion Criteria:

• Diagnosis of sickle cell disease confirmed through hemoglobin electrophoresis
• Genotypes SS, SC and Sβ thalassemia
• Age > 1 year

Exclusion Criteria:

• Liver dysfunction (alanine aminotransferase ALT > 3 times the normal levels
• Renal dysfunction (creatinine > twice the normal levels)
• Increase in methemoglobin levels (> 5 times the normal levels)
• History of recent stroke (< 1 month) and priapism
• Pregnancy
• Allergy to L-arginine
• Use of sildenafil, calcium channel blockers, nitroglycerin or other nitrates