Table 1.
Characteristics of the studies included in this systematic review and meta‐analysis.
| First author | Country | Study design | Sample size (arms of study) | Patients' characteristics (arms of study) | Male (%) |
Age (years) Mean (±SD) |
HbSS (%) | Intervention type | Duration | Endpoints |
|---|---|---|---|---|---|---|---|---|---|---|
| Saka et al. 32 | Nigeria | Clinical trial | 80 (40/40) | SCA adults in steady state/healthy adults | 50 | 29.4 ± 6.9 | 100 | PO l‐arginine, 1000 mg QD | 6 weeks | Fasting blood glucose and insulin, glycated hemoglobin, glucose transporter 1, oxidative stress marker level, plasma amino acid level, plasma NO metabolites |
| Onalo et al. 10 | Nigeria | RCT | 66 (35/31) | SCA children in nonsteady state | 57.6 | 10.6 ± 3.4 | 100 | PO l‐arginine, 100 mg/kg TID | 5 days or till discharge | Anthropometric indices, pain severity, plasma aminoacid levels, vital signs |
| Temiye et al. 9 | Nigeria | Single arm trial | 22 | SCD children in steady state | NM | 5.6 ± 5.1 | NM | PO l‐arginine, 500 mg QD | 6 weeks | Anthropometric indices, antioxidant enzymes, CBC, LFT, oxidative stress marker level, vital signs |
| Morris et al. 14 | USA | RCT | 12 | SCD children in nonsteady state | 67 | 13.6 ± 3 | 75 | Randomized to 1 of 3 IV l‐arginine doses: | 7 days or till discharge | Mitochondrial activity and DNA, oxidative stress markers level |
| 1–100 mg/kg TID | ||||||||||
| 2–200 mg/kg as loading and then 100 mg/kg TID | ||||||||||
| 3–200 mg/kg as loading and then 300 mg/kg infusion daily | ||||||||||
| Eleutério et al. 13 | Brazil | RCT | 50 (25/25) | SCA adults in steady state | 48 | 28 ± 9 | 100 | PO l‐arginine, 500 mg QD | 4 months | CBC, HbF, hospitalization frequency, plasma NO metabolites, reticulocyte count, pain frequency |
| Abubakar et al. 31 | Nigeria | RCT | 60 (30/30) | SCA children in steady state | NM | 7.5 ± 3.9 | 100 | PO l‐arginine, 700–3500 mg BID (based on body weight) | 8 weeks | Plasma aminoacid levels, plasma NO metabolites |
| Jaja et al. 7 | Nigeria | Clinical trial | 40 (20/20) | SCA adults in steady state/healthy adults | NM | 24.5 ± 5.4 | 100 | PO l‐arginine, 1000 mg QD | 6 weeks | Anthropometric indices, CBC, LFT, oxidative stress marker level, plasma amino acid level, plasma NO metabolites |
| Kehinde et al. 35 | Nigeria | Single arm trial | 28 | SCA adults in steady state | 50 | 24.5 ± 6.3 | 100 | PO l‐arginine, 1000 mg QD | 6 weeks | Antioxidant enzymes, CBC, irreversibly sickled cells percentage, oxidative stress marker level, plasma aminoacid level, osmotic fragility |
| Morris et al. 34 | USA | RCT | 54 (26/28) | SCD children in nonsteady state | 48.1 | 13.9 ± 4 | 74 | PO/IV l‐arginine, 100 mg/kg TID with a maximum dose of 10 g for 15 doses | 5 days or till discharge | CBC, hospital length of stay, LFT, pain severity, total opioid use, reticulocyte count |
| Elias et al. 8 | Brazil | RCT | 21 (12/9) | SCA adults in steady state | 42.8 | NM | 100 | PO l‐arginine, 250 mg QD | 3 months | CBC, HbF, plasma NO metabolites, reticulocyte count |
| Little et al. 33 | USA | Clinical trial | 27 (13/14) | SCA adults in steady state/SCA adults in steady state | 40.7 | 38.4 ± 9.4 | 100 | 1‐ PO l‐arginine, 100–200 mg ⁄kg divided TID in one arm2‐ PO sildenafil, 25–100 mg TID in the other arm | 12 weeks | Arginase activity, CBC, echocardiographic indices, HbF, 6 min walk test, plasma aminoacid levels, reticulocyte count |
| Morris et al. 30 | USA | Clinical trial | 5 | SCA children in steady state | 20 | 16.2 ± 4 | 100 | PO l‐arginine, 100 mg/kg | Single dose | Arginase activity, exhaled NO, plasma aminoacid levels, plasma NO metabolites |
Abbreviations: BID, two times a day; CBC, cell blood count; DNA, deoxyribonucleic acid; HbF, fetal hemoglobin; IV, intravenous; LFT, liver function tests; NM, not mentioned; NO, nitric oxide; PO, oral; QD, once daily; RCT, randomized clinical trial; SCA, sickle cell anemia; SCD, sickle cell disease; SD, standard deviation; TID, three times a day.