Table 1.
Placebo- and active controlled studies investigating intravaginal clotrimazole in women with uncomplicated (acute) vulvovaginal candidosis.
| Reference and Population | Design | Fungal Verification Method | Candida Species | Drug and Formulation | Regimen | Outcomes | Adverse Events |
|---|---|---|---|---|---|---|---|
| [26] Adolescents ≥16 y and adults |
r, db, pc | Culture and microscopy | C. albicans | CLO vaginal tablet or placebo |
CLO: 500 mg, single dose, n = 10 Placebo: n = 13 |
Mycological cure rate at D 5–31 after Rx (CLO vs. placebo): 90% vs. 0%, p = 0.0001 Clinical cure rate at D 5–31 after Rx (CLO vs. placebo): 90% vs. 0%, p = 0.0001 |
None occurred |
| [27] Adolescents ≥16 y and adults |
r, db, pc, mc | Culture | C. albicans (65% of subjects) | CLO vaginal tablet or placebo |
CLO: 500 mg, single dose, n = 55 Placebo: n = 40 |
Mycological cure rate at W 1 after Rx (CLO vs. placebo): 62% vs. 25%, p < 0.001 |
nr |
| [28] Adults |
r, db *, pc, ac | Culture and microscopy | C. albicans (98% of subjects) | CLO vaginal tablet or oral itraconazole capsule or oral placebo capsule |
CLO: 200 mg/d for 3 d, n = 20 Itraconazole: 200 mg/d for 3 d, n = 48 Placebo for 3 d, n = 22 |
Mycological cure rate at W 1 after Rx (CLO vs. itraconazole vs. placebo): 95% vs. 73% vs. 32%, p < 0.005 for CLO vs. placebo Mycological cure rate at W 4 (CLO vs. itraconazole vs. placebo): 83% vs. 89% vs. 57%, p < 0.05 for CLO vs. placebo Clinical cure rate at W 1 after Rx (CLO vs. itraconazole vs. placebo): 65% vs. 73% vs. 45%, p < 0.05 for CLO vs. placebo Clinical cure rate at W 4 (CLO vs. itraconazole vs. placebo): 61% vs. 77% vs. 57%, ns for CLO vs. placebo, ns for CLO vs. itraconazole |
CLO: 1 subject with AEs Itraconazole: 17 subjects with AEs Placebo: 9 subjects with AEs |
| [29] Adults |
r, o, ac, mc | Culture and microscopy | C. albicans (93% of subjects) | CLO vaginal tablet or oral fluconazole capsule |
CLO: 200 mg qd for 3 d, n = 181 Fluconazole: 150 mg, single dose, n = 188 |
Mycological cure rate at D 5–16 after Rx (CLO vs. fluconazole): 81% vs. 85%, ns Mycological cure rate at D 27–62 (CLO vs. fluconazole): 62% vs. 72%, ns |
CLO: 9 subjects with mild AEs Fluconazole: 8 subjects with mild AEs |
| [30] Adolescents ≥15 y and adults |
r, o, ac | Culture and microscopy | C. albicans | CLO vaginal tablet or oral fluconazole capsule |
CLO: 500 mg, single dose, n = 20 Fluconazole: 150 mg, single dose, n = 23 |
Mycological cure rate at D 8 after Rx (CLO vs. fluconazole): 75% vs. 87%, p = 0.05 Mycological cure rate at D 32 (CLO vs. fluconazole): 60% vs. 87%, p = 0.05 |
CLO: 2 subjects with mild AEs Fluconazole: 1 subject with mild AEs |
| [31] Adults |
r, o, ac, mc | Culture | nr | CLO vaginal tablet or oral fluconazole capsule |
CLO: 200 mg qd for 3 d, n = 95 Fluconazole: 50 mg qd for 3 d, n = 90 |
Mycological cure rate at D 7–10 after Rx (CLO vs. fluconazole): 93% vs. 89%, nc Mycological cure rate at D 30–35 (CLO vs. fluconazole): 86% vs. 77%, nc Clinical cure rate at D 7–10 after Rx (CLO vs. fluconazole): 88% vs. 84%, nc Clinical cure rate at D 30–35 (CLO vs. fluconazole): 83% vs. 79%, nc Mycological cure rate at D 6–8 after Rx (CLO vs. fluconazole): 84% vs. 86%, ns |
CLO: 5 subjects with mild/moderate AEs Fluconazole: 12 subjects with mild/moderate AEs One subject on fluconazole discontinued due to diarrhea |
| [32] Adolescents ≥16 y and adults |
r, o, ac, mc | Culture and microscopy | C. albicans (92% of subjects) | CLO vaginal tablet + CLO external 1% cream or oral fluconazole capsule |
CLO: 500 mg, single dose + cream on vulva bid, n = 92 Fluconazole: 150 mg, single dose, n = 93 |
Mycological cure rate at D 28–32 (CLO vs. fluconazole): 85% vs. 89%, ns Clinical cure rate at D 6–8 after Rx (CLO vs. fluconazole): 80% vs. 87%, ns Clinical cure rate at D 28–32 (CLO vs. fluconazole): 84% vs. 92%, ns |
CLO: 3 subjects with AEs Fluconazole: 2 subjects with AEs |
| [33] Adults |
r, o, ac, mc | Culture | nr | CLO vaginal tablet or oral fluconazole capsule |
CLO: 500 mg, single dose Fluconazole: 150 mg, single dose Total n = 537 |
Mycological cure rate at D 7 after Rx (CLO vs. fluconazole): 76% vs. 82%, ns Mycological cure rate at D 28 (CLO vs. fluconazole): 72% vs. 75%, ns |
CLO: 110 AEs Fluconazole: 112 AEs Both drugs well accepted |
| [34] | r, o, ac | Culture and microscopy | nr | CLO vaginal tablet or oral fluconazole |
CLO: 100 mg qd for 6 d, n = 50 Fluconazole 1: 50 mg qd for 6 d, n = 90 Fluconazole 2: 150 mg, single dose, n = 50 |
Mycological cure rate at D 5–15 after Rx (CLO vs. fluconazole 1 vs. fluconazole 2): 72% vs. 88% vs. 76%, nc Mycological cure rate at D 30–60 (CLO vs. fluconazole 1 vs. fluconazole 2): 60% vs. 80% vs. 70%, nc Clinical cure rate at D 5–15 after Rx (CLO vs. fluconazole 1 vs. fluconazole 2): 72% vs. 92% vs. 80%, ns Clinical cure rate at D 30–60 (CLO vs. fluconazole 1 vs. fluconazole 2): 58% vs. 88% vs. 76%, ns |
None occurred |
| [35] Adults |
r, sb, ac, mc | Culture | C. albicans (85–88% of subjects) | CLO vaginal tablet or oral fluconazole capsule |
CLO: 100 mg qd for 7 d, n = 214 Fluconazole: 150 mg, single dose, n = 218 |
Mycological cure rate at D 14 after start of Rx (CLO vs. fluconazole): 72% vs. 77%, ns Mycological cure rate at D 35 (CLO vs. fluconazole): 57% vs. 63%, ns Clinical cure rate at D 14 after start of Rx (CLO vs. fluconazole): 67% vs. 73%, ns Clinical cure rate at D 35 (CLO vs. fluconazole): 75% vs. 75%, ns |
CLO: 37 subjects with mild/moderate AEs Fluconazole: 59 subjects with mild/moderate AEs |
| [36] Adults |
r, sb, ac | Culture | nr | CLO vaginal tablet or oral fluconazole capsule | CLO: 100 mg bid for 3 d, n = 50 Fluconazole: 150 mg, single dose, n = 53 |
Mycological cure rate at W 1 after Rx (CLO vs. fluconazole): 80% vs. 79%, ns Mycological cure rate at W 4 (CLO vs. fluconazole): 66% vs. 60%, ns |
CLO: 11 subjects had mild vaginal burning sensations Fluconazole: 4 subjects with mild nausea or dizziness |
| [37] Adolescents ≥16 y and adults |
r, sb, ac | Culture and microscopy | nr | CLO vaginal tablet + CLO external 1% cream or oral fluconazole or oral itraconazole | CLO: 500 mg, single dose, n = 82 Fluconazole: 150 mg, single dose, n = 72 Itraconazole: 200 mg bid for 1 d, n = 75 |
Mycological cure rate at D 7–10 (CLO vs. fluconazole vs. itraconazole): 95% vs. 83% vs. 96%, p = 0.033 for CLO vs. fluconazole Clinical cure rate at D 7–10 (CLO vs. fluconazole vs. itraconazole): 80% vs. 62% vs. 80%, p = 0.027 for CLO vs. fluconazole |
nr |
| [38] Adults |
r, o, ac | Culture and microscopy | nr | CLO vaginal tablet or oral fluconazole or oral itraconazole | CLO: 100 mg qd for 6 d, n = 50 Fluconazole: 150 mg, single dose, n = 50 Itraconazole: 200 mg qd for 3 d, n = 50 |
Mycological cure rate at D 5–15 after Rx (CLO vs. fluconazole vs. itraconazole): 72% vs. 76% vs. 80%, nc Mycological cure rate at D 30–60 (CLO vs. fluconazole vs. itraconazole): 60% vs. 70% vs. 74%, nc Clinical cure rate at D 5–15 after Rx (CLO vs. fluconazole vs. itraconazole): 72% vs. 80% vs. 84%, nc Clinical cure rate at D 30–60 (CLO vs. fluconazole vs. itraconazole): 58% vs. 76% vs. 78%, nc |
None occurred |
| [21] nr |
r, sb, ac, mc | Culture and microscopy | C. albicans (95% of subjects) | CLO vaginal tablet + 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 |
| [39] Adolescents >15 y and adults |
r, o, ac | Microscopy | nr | CLO vaginal tablet or oral fluconazole |
CLO: 200 mg qd for 6 d, n = 70 Fluconazole: 150 mg, single dose, n = 72 |
Mycological cure rate at D 7 after Rx (CLO vs. fluconazole): 70% vs. 83%, p = 0.01 Clinical cure rate at D 7 after Rx (CLO vs. fluconazole): 59% vs. 74%, p = 0.001 |
CLO: pelvic pain Fluconazole: headache No difference in AE frequencies |
| [40] Adolescents ≥16 y and adults |
r, sb, ac, mc | Culture | nr | CLO vaginal tablet or oral ketoconazole |
CLO: 100 mg qd for 6 d, n = 29 Ketoconazole: 200 mg bid for 5 d, n = 34 |
Mycological cure rate at W 2 (CLO vs. ketoconazole): 86% vs. 83%, nc |
CLO: 1 subject with AEs Ketoconazole: 5 subjects AEs |
| [41] Adolescents ≥16 y and adults |
r, o, ac | Culture and microscopy | C. albicans (96% of subjects) | CLO vaginal ovule or oral ketoconazole or CLO + lactic acid in vaginal ovule | CLO: 500 mg, single dose, n = 25 Ketoconazole: 200 mg bid for 5 d, n= 25 CLO + lactic acid: 500 mg, single dose, n = 25 |
Mycological cure rate at W 3 after Rx (CLO vs. ketoconazole vs. CLO + lactic acid): 84% vs. 76% vs. 92%, nc |
nr |
| [42] Adults |
r, sb, ac, mc | Culture | nr | CLO vaginal tablet or oral itraconazole capsule |
CLO: 500 mg, single dose, n = 105 Itraconazole: 200 mg bid for 1 d, n = 109 |
Mycological cure rate at W 1 after Rx (CLO vs. itraconazole): 72% vs. 74%, ns Mycological cure rate at W 6 (CLO vs. itraconazole): 50% vs. 51%, ns |
nr |
ac: active-controlled; AEs: adverse events; bid: twice-daily; CLO: clotrimazole; d or D: day; db: double-blind; M: month; 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; y: year. * Comparison with clotrimazole was not blinded.