Table 2.
Randomized controlled studies comparing different treatment regimens or formulations of intravaginal clotrimazole in women with uncomplicated (acute) vulvovaginal candidosis.
| Reference and Population | Design | Fungal Verification Method | Candida Species | Formulations | Regimen | Outcomes | Adverse Events |
|---|---|---|---|---|---|---|---|
| [43] Adults |
r, db, ac | Culture | C. albicans | CLO vaginal tablet 500 mg or CLO vaginal tablet 200 mg |
CLO 1: 500 mg, single dose, n = 35 CLO 2: 200 mg qd for 3 d, n = 37 |
Mycological cure rate at D 7 after Rx (CLO 1 vs. CLO 2): 94% vs. 89%, ns Clinical cure rate at W 4 after Rx (CLO 1 vs. CLO 2): 86% vs. 92%, ns |
None occurred |
| [44] Adults |
r, db, ac, mc | Culture and microscopy | nr | CLO vaginal tablet 500 mg or CLO vaginal tablet 100 mg |
CLO 1: 500 mg, single dose, n = 53 CLO 2: 2 × 100 mg qd for 3 d, n = 50 |
Mycological + clinical cure rate at D 5–10 after Rx (CLO 1 vs. CLO 2): 90% vs. 89%, ns Mycological + clinical cure rate at ≥D 27 (CLO 1 vs. CLO 2): 75% vs. 72%, ns |
CLO 2: 1 subject had moderate edema of vulva |
| [45] Adults |
r, db, ac | Culture and microscopy | nr | CLO vaginal tablet 500 mg or CLO vaginal tablet 100 mg |
CLO 1: 500 mg, single dose, n = 18 CLO 2: 2 × 100 mg qd for 3 d, n = 18 |
Mycological + clinical cure rate at M 1 after Rx (CLO 1 vs. CLO 2): 89% vs. 83%, ns | CLO 2: 1 subject had moderate edema of vulva |
| [46] Adults |
r, db, ac | Culture and microscopy | C. albicans | CLO vaginal tablet 500 mg or CLO vaginal tablet 100 mg |
CLO 1: 500 mg, single dose, n = 14 CLO 2: 2 × 100 mg qd for 3 d, n = 13 |
Mycological + clinical cure rate at M 1 after Rx (CLO 1 vs. CLO 2): 86% vs. 85%, ns | None occurred |
| [47] Adults |
r, db, ac | Culture and microscopy | nr | CLO vaginal tablet 500 mg or CLO vaginal tablet 100 mg |
CLO 1: 500 mg, single dose, n = 20 CLO 2: 100 mg qd for 6 d, n = 20 |
Mycological cure rate at D 3 after Rx (CLO 1 vs. CLO 2): 85% vs. 95%, nc Mycological cure rate at W 4 after Rx (CLO 1 vs. CLO 2): 95% vs. 80%, nc |
1 subject reported vaginal burning |
| [21] nr |
r, sb, ac, mc | Culture and microscopy | C. albicans (95% of subjects) | CLO vaginal tablet 500 mg + CLO external 1% cream (VT) or CLO 10% vaginal cream + CLO external 2% cream (VC) or oral fluconazole capsule |
CLO VT: 500 mg, single dose, n = 226 CLO VC: 1 tube, single dose, n = 226 Fluconazole: 150 mg, single dose, n = 227 |
Mycological cure rate at D 14 (CLO VT vs. CLO VC vs. fluconazole): 80% vs. 74% vs. 76%, CLO VT and CLO VC non-inferior to fluconazole Clinical cure rate at D 14 (CLO VT vs. CLO VC vs. fluconazole): 66% vs. 61% vs. 59%, CLO VT and CLO VC non-inferior to fluconazole |
CLO VT: 26 subjects with mild AEs CLO VC: 32 subjects with mild AEs Fluconazole: 29 subjects with mild AEs |
| [48] Adolescents ≥16 y and adults |
r, o, ac | Culture | C. albicans | CLO 10% cream or CLO 2% cream |
CLO 10%: 5 g, single dose, n = 55 CLO 2%: 5 g, bid for 3 d, n = 55 |
Mycological cure rate at D 7 after start of Rx (CLO 10% vs. CLO 2%): 91% vs. 96%, nc Mycological cure rate at D 35 (CLO 10% vs. CLO 2%): 84% vs. 81%, nc |
None occurred |
| [49] Adolescents ≥14 y and adults |
r, o, ac | Culture and microscopy | C. albicans (96% of subjects) | CLO 10% cream or CLO vaginal tablet 500 mg (VT) |
CLO 10%: 5 g, single dose, n = 81 * CLO VT: 500 mg, single dose, n = 82 # |
Mycological cure rate at W 1 after Rx (CLO 10% vs. CLO VT): 85% vs. 87%, ns Mycological cure rate at W 4 after Rx (CLO 10% vs. CLO VT): 73% vs. 80%, nc Clinical cure rate at W 1 after Rx (CLO 10% vs. CLO VT): 94% vs. 91%, ns Clinical cure rate at W 4 after Rx (CLO 10% vs. CLO VT): 85% vs. 94%, nc |
CLO 10%: 3% of subjects had mild AEs |
| [22] Adults |
r, db, pc, mc | Culture and microscopy | nr | CLO vaginal suppository 200 mg + CLO external 2% cream (T1) or CLO vaginal suppository 200 mg + placebo external cream (T2) |
CLO 1 (T1): 200 mg, qd for 3 d, n = 79 CLO 2 (T2): 200 mg qd for 3 d, n = 79 Cream was applied to the vulva |
Mycological cure rate (vagina) at D 6 after Rx (CLO 1 vs. CLO 2): 92% vs. 90%, ns Mycological cure rate (vulva) at D 6 after Rx (CLO 1 vs. CLO 2): 73% vs. 52%, p = 0.005 Mycological cure rate (vagina) at W 4 (CLO 1 vs. CLO 2): 23/25 (92%) vs. 21/23 (91%), ns Mycological cure rate (vulva) at W 4 (CLO 1 vs. CLO 2): 16/23 (70%) vs. 13/21 (62%), ns |
CLO 1: 1 subject reported vaginal burning CLO 2: 1 subject reported skin peeling With CLO 1, significantly less local itching and extravaginal redness |
| [50] Adolescents ≥14 y and adults |
r, sb, ac, mc | Culture and microscopy | nr | CLO ovule 500 mg (O) or CLO vaginal tablet 500 mg (VT) |
CLO 1 (O): 500 mg, single dose, n = 237 CLO 2 (VT): 500 mg, single dose, n = 228 |
Mycological cure rate at W 2 after Rx (CLO 1 vs. CLO 2): 81% vs. 78%, ns Mycological cure rate at W 6–8 (CLO 1 vs. CLO 2): 78% vs. 81%, ns Clinical cure rate at W 2 after Rx (CLO 1 vs. CLO 2): 88% vs. 84%, ns Clinical cure rate at W 6–8 (CLO 1 vs. CLO 2): 93% vs. 93%, ns |
CLO 1: 1 subject reported a mild drug-related AE (vulvovaginal discomfort) |
ac: active-controlled; AEs: adverse events; bid: twice-daily; CLO: clotrimazole; d or D: day; db: double-blind; mc: multicenter; n: number of subjects; nc: not compared; nr: not reported; ns: not statistically significant; o: open; pc: placebo-controlled; qd: once-daily; r: randomized; Rx: treatment; sb: single-blind; W: week. * Seven women were pregnant; # One woman was pregnant.