TABLE 5.
Characteristics of included studies—Podiatry.
| Author; year of publication; trial registration | Study design; country; setting | Participant characteristics | Eligibility criteria | Interventions; comparisons | Outcome measures (methods); timepoints | Main findings | Safety | Funding; conflict of interest |
|---|---|---|---|---|---|---|---|---|
| Onychomycosis | ||||||||
| Buck; 1994; trial not registered Buck et al. (1994) | RCT (parallel); United States; Hospital and community outpatient clinics | N = 117 enrolled (n = 108 analysed) | Inclusion criteria: distal subungual toenail onychomycosis confirmed by culture | Intervention group: TTO (100% TTO, Melaleuca alternifolia), Thursday Plantation Inc., US. | Clinical assessment (clinician assessed toenail with greatest fungal involvement as “full”, “partial” or “no” resolution) | Clinical assessment—no difference between proportions of subjects in TTO group and control group with full or partial resolution of onychomycosis (24/40 vs. 22/36) | Adverse reactions including erythema, irritation and oedema were experienced by: TTO group 5/64 | Funding: Schering-Plough Corp, US and Thursday Plantation Inc. US |
| Age in years, mean | Exclusion criteria: topical agent applied to toenails within 2 weeks prior to study; immunosuppressant drug use within 6 months prior to study; history of psoriasis; known HIV infection | Subjects applied twice daily for 6 months. Note: dose not stated | Timepoints: Baseline and at 1, 3 and 6 months | Fungal culture test—no difference between proportions of subjects with negative culture in TTO group and control group (7/39 vs. 4/36) | Control group 3/53 | Conflicts of interest: no data provided | ||
| TTO group 61 | Control group: 1% clotrimazole solution, Schering-Plough Corp, US. | Fungal culture test (assessed by dermatophyte infection test medium) | Subjective assessment—no difference in proportion of subjects in TTO group and control group reporting resolution or improvement 3 months after discontinuation of therapy (33/59 vs. 27/49) | |||||
| Control group 59 | Subjects applied twice daily for 6 months. Note: dose not stated | Timepoints: Baseline and post-treatment (i.e., at 6 months) | Note: no statistically sig. differences found between the two treatments using chi-square statistic | |||||
| Female TTO group 49/64 | At 1-, 3- and 6-month assessments subjects’ toenails were trimmed and debrided | Subjective assessment (patient-reported appearance and symptoms i.e., pruritis and pain, as resolved, improved, stayed the same or worsened) | ||||||
| Control group 38/53 | Timepoint: 3 months after cessation of treatment (i.e., after 9 months) | |||||||
| Tinea pedis | ||||||||
| Satchell; 2002; trial not registered Satchell et al. (2002b) | RCT (parallel); Australia; Community | N = 137 enrolled (n = 120 analysed) | Inclusion criteria: intertriginous tinea pedis; age ≥14 years; dermatophyte infection evident from microscopy examination | Intervention group 1 | Mycological cure (assessed by culture of skin scrapings) | Mycological cure (i.e., negative culture) was achieved in sig. greater proportion of subjects in 50% TTO group (23/36) and 25% TTO group (18/33), compared with placebo group (14/45), after 4 weeks (p < 0.01) | Moderate to severe dermatitis occurred in one patient applying 25% TTO and 3 patients applying 50% TTO (this improved on stopping the study medication) | Funding: Australian Tea Tree Oil Research Institute, Australia |
| Age in years, range 17–83; mean TTO 50% group 45 | Exclusion criteria: systemic antifungal drug use within 6 months prior to study; topical antifungal drug use within 7 days prior to study; dermatitis; immune-suppressed; known hypersensitivity to TTO. | 50% TTO solution (50% TTO, Melaleuca alternifolia); mixed with ethanol and polyethylene glycol | Timepoints: Baseline and after 4 weeks | Clinical signs and symptoms—marked improvement achieved in sig. greater proportion of subjects in 50% TTO group (26/38) and 25% TTO group (26/36), compared with placebo group (18/46), after 4 weeks (p < 0.005) | Stinging (burning) on application reported by 2 subjects in 25% TTO group and 2 subjects in placebo group | Conflicts of interest: no data provided | ||
| TTO 25% group 38 | Intervention group 2: 25% TTO solution (25% TTO, Melaleuca alternifolia); mixed with ethanol and polyethylene glycol | Clinical signs and symptoms (two investigator-assessed items: scaling and inflammation and two patient-assessed items: burning and itching, were each scored separately as 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. All four items were then summed. Marked improvement was defined as a final clinical score of 0 or reduction of ≥ 3 to a final value < 3) | ||||||
| Control group 39 | Control group: placebo (20% ethanol, 80% polyethylene glycol) | Timepoints: Baseline and after weeks 2 and 4 | ||||||
| Female TTO 50% group 14/51 | Subjects applied allocated solution twice daily for 4 weeks. All subjects washed feet with soap and water, dried and then applied their allocated solution. Subjects were instructed not to use other antifungal treatments during the study | |||||||
| TTO 25% group 20/54 | ||||||||
| Control group 20/53 | ||||||||
| Tong; 1992; trial not registered Tong et al. (1992) | RCT (parallel); Australia; Not described | N = 121 enrolled (n = 104 analysed)Age in years, median (range)TTO group 30 (18–60)Tolnaftate group 30 (20–57)Placebo group 34 (19–65)Female TTO group 13/37Tolnaftate group 11/33Placebo group 1/34 | Inclusion criteria: diagnosed tinea pedis (based on microscopy examination or fungal culture); age 16–65 yearsExclusion criteria: systemic antifungal drug use within 6 months prior to study; topical antifungal drug use within 1 week prior to study; medical condition or medication use increasing risk for fungal infection | Intervention group: TTO cream (10% w/w TTO, Melaleuca alternifolia). Other ingredients: sorbolene creamTTO cream produced by Pharmaco Pty Ltd., AustraliaControl group 1: 1% tolnaftate cream (Tinaderm®, Schering Pty Ltd., Australia)Control group 2: placebo (sorbolene cream—vehicle cream)All subjects applied allocated cream twice daily for 4 weeks | Mycological cure (assessed by culture of skin scrapings)Timepoints: Baseline and at week 4 (i.e., end of treatment)Clinical signs and symptoms (two investigator-assessed items: scaling and inflammation and two patient-assessed items: burning and itching, were each scored separately as 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. All four items were then summed. Clinical improvement defined as an improvement in clinical score > 2 points)Timepoints: Baseline and at weeks 1, 2, 3 and 4 (i.e., end of treatment) | Mycological cure (i.e., negative culture) achieved in sig. greater proportion of subjects in tolnaftate group (28/33) compared with TTO group (11/37) and placebo group (7/34), after 4 weeks (p < 0.001). Difference not sig. between TTO group and placebo, after 4 weeks (p = 0.393)Clinical signs and symptoms sig. improvement in TTO group (24/37), compared with placebo group (14/34), after 4 weeks (p = 0.022) | Mild erythema developed in one subject from tolnaftate groupNo patient dropped out due to adverse side effects | Funding: Australian Rural Industries Research and Development Corporation and the Australian Tea Tree Oil Industry AssociationConflicts of interest: no data provided |
Abbreviations: HIV, human immunodeficiency virus; RCT, randomised controlled trial; TTO, tea tree oil; US, United States.