A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments.     

A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea

In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either 1% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. One per cent metronidazole cream has been shown to be significantly better than a placebo cream in the treatment of rosacea (Gamborg Nielsen, 1983a), It was therefore considered important to compare the cream with conventional therapy, and for this reason a double-blind study of 1% metronidazole cream versus a daily dose of 500 mg oxytetracycline was performed.     

Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea

BACKGROUND: The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance. OBJECTIVE: We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen. METHODS: A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12. RESULTS: There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents. CONCLUSION: This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea.     

Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study

BACKGROUND: Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea. METHODS: This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected. RESULTS: The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules. CONCLUSION: It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.     

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea

Background: Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea. Objective: The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea. Methods: One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period. Results: Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo. Conclusions: The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.     

Topical 5-aminosalicylic acid: a treatment for aphthous ulcers

A double-blind placebo controlled trial of 5% 5-aminosalicylic acid (5-ASA) cream for the treatment of oral aphthous ulcers was carried out on 22 subjects. The cream or a placebo (11 patients each) was applied to the ulcers three times daily for up to 14 days. Daily discomfort was reduced by half (P less than 0.01) and less pain (P less than 0.05) was experienced by the treated group. Treatment with 5-ASA shortened healing time (7 vs. 11 days, P less than 0.01) and reduced the difficulty in eating (P less than 0.05). No significant side-effects were reported. We believe 5-ASA cream to be an effective treatment for aphthous ulcers.     

Topical treatment of recurrent genital herpes simplex virus infections with trisodium phosphonoformate (foscarnet): double blind, placebo controlled, multicentre study.

A double blind, placebo controlled trial was performed in nine sexually transmitted diseases (STD) clinics in the United Kingdom and the Netherlands to investigate the efficacy of trisodium phosphonoformate (foscarnet) cream in treating recurrent genital herpes simplex virus (HSV) infection. The study group comprised 145 male and 85 female patients. Men received 0.3% foscarnet cream and women 1% foscarnet cream for five days. The difference in time to healing between patients receiving foscarnet or placebo was not significant. Fewer patients treated with foscarnet had positive viral cultures after treatment, but the difference was not significant. The development of new lesions, however, was significantly less common in patients given foscarnet. Though topical foscarnet is a safe drug, no appreciable efficacy in treating recurrent genital HSV infection could be shown.     

Topical Metronidazole Gel

Two percent metronidazole and 5% benzoyl peroxide cream was evaluated in four clinical trials. It could be shown that this test cream was significantly better than 5% benzoyl peroxide jelly alone, and significantly better than a placebo cream. It was also shown that 2% metronidazole and 5% benzoyl peroxide cream was equal to systemic oxytetracycline therapy. The advisability of the combination of metronidazole and benzoyl peroxide was simultaneously discussed.     

A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.     

A comparison of acyclovir cream versus placebo cream versus liquid nitrogen in the treatment of viral plantar warts

52 patients with a clinical diagnosis of verruca plantaris were entered into a randomised study of acyclovir cream versus placebo cream versus liquid nitrogen. 47 completed the initial 8-week assessment period. At first, liquid nitrogen was used as a positive control but after the entry of 33 patients it was discontinued as an initial therapy in order to obtain maximal numbers of patients on the cream treatments. At the end of the 8-week assessment period 5 of 18 (placebo cream), 7 of 18 (acyclovir cream) and 1 of 11 (liquid nitrogen) patients were completely cleared of their plantar warts. Patients who failed to clear on cream or liquid nitrogen treatments after the initial assessment period but who wished to continue therapy were subsequently treated with liquid nitrogen. Of a total of 27 patients treated vigorously with liquid nitrogen, for periods of time ranging from 2 to 34 weeks, only 11 were completely cleared of their warts at the end of the study. It is concluded that liquid nitrogen should not be considered as a routine treatment for plantar warts and that acyclovir cream is no better than placebo in the treatment of this condition.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.     

Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial.

OBJECTIVE--To compare the effect of lactic acid locally, metronidazole orally and placebo in women with bacterial vaginosis. DESIGN--Randomised clinical trial. SETTING--30 general practices in the Netherlands. PATIENTS--125 women consulting the general practitioner for symptomatic bacterial vaginosis. MAIN OUTCOME MEASURES--Duration of subjective symptoms, recurrence of symptoms, clinically diagnosed cure, adverse events. RESULTS--Survival analysis showed a significantly faster disappearance of symptoms in the metronidazole category compared with both lactic acid and placebo (p = 0.0005 metronidazole v placebo, p = 0.0002 metronidazole v lactic acid p = 0.6521 lactic acid v placebo [The stratified Mantel Cox test]). The median duration until absence of symptoms was 21 days for metronidazole and 80 days for placebo. Disappearance of symptoms did not occur in 50% of the lactic acid group in 90 days. Recurrence rates of symptoms were similar over the treatment categories (p = 0.13 metronidazole v placebo and p = 0.12 lactic acid v placebo). After 2 weeks cure rates (cure defined as less than three of four clinical criteria present) were 83%, 49% and 47% for metronidazole, lactic acid and placebo category respectively. At that time cure rates (cure defined as none of three clinical criteria present) were 10%, 0% and 3%. After four weeks and three months these figures were: 55%, 20%, 20% and 64%, 28%, 28%. No differences in adverse events were found between the three interventions. CONCLUSIONS--Lactic acid suppositories are ineffective, metronidazole capsules are effective on signs and symptoms in bacterial vaginosis. A considerable proportion of the patients recover without active medication.     

The use of a corticosteroid cream for immediate reduction in the clinical signs of acne vulgaris

A controlled trial of the anti-inflammatory effect of a steroid cream (clobetasol propionate) in 11 patients with moderate acne was assessed over a 3 week period. The placebo cream was the base of the steroid cream. Therapeutic effect was assessed by the number of active and less actively inflamed papules and pustules present at the beginning and end of the 3 week trial period. No significant change in lesion counts was observed. This result indicates that a potent topical steroid cream produces no short-term improvement in patients with moderate acne.     

Researching accessible and affordable treatment for common dermatological problems in developing countries. An Ethiopian experience

Background Skin diseases are very common in rural and urban areas of Ethiopia, and traditional preparations of plant origin might represent the only alternative to synthetic drugs. Improving knowledge of traditional medicines and assessing their safety and effectiveness is necessary. Methods We conducted a two‐arm, randomized, double‐blind, placebo‐controlled trial assessing the efficacy of some cosmetic herbal preparations for common dermatologic problems: a 3% thyme essential oil antifungal cream and a 10% chamomile extract cream for eczema‐like lesions. Results Ten subjects (66.5%) treated with the 3% thyme active cream were completely healed vs. four subjects (28.5%) from the placebo group (P = 0.040). A large number of subjects treated with the chamomile cream were healed or improved, but no significant differences were found between active cream and placebo. A high rate of treatment acceptance was registered in both groups, no adverse effects were reported. Conclusions A 3% thyme essential oil cream could represent a cheap and easily available opportunity to treat and heal mild to moderate cases of fungal infections; a common emollient cream could be a very effective intervention when treating mild to moderate cases of pityriasis alba and eczema‐like lesions. Further research is needed.     

The retinoic acid derivative Ro 11-1430 (Tasmaderm) in patients with acne vulgaris not tolerating retinoic acid. A controlled multicenter trial against placebo.

In a double-blind randomized comparative multicenter trial, consisting of 29 patients with acne vulgaris who were unable to tolerate daily applications of retinoic acid, the retinoic acid derivative Ro 11--1430 (0.1% vanishing cream) was compared in a 6--8 weeks topical treatment with vanishing cream alone (placebo). Regarding efficacy, for most criteria measured the response was always better with Ro 11--1430 than with placebo, although the differences were not always statistically significant for several reasons, one probably being the small number of patients in the trial. Regarding tolerance, both treatments were satisfactory. Ro 11---1430 and placebo did not differ significantly regarding frequency and severity of erythema, desquamation and burning. These results suggest that treatment with Ro 11--1430 should be considered in acne patients who are unable to use retinoic acid due to severe local reactions.     

Topical metronidazole in seborrheic dermatitis--a double-blind study

OBJECTIVE: To evaluate the role of topical metronidazole gel in the treatment of seborrheic dermatitis. METHODS: Forty-four patients with seborrheic dermatitis were enrolled in the study. All topical treatments were stopped for at least 2 weeks before the patients were allocated at random to receive either metronidazole 1% gel or placebo for 8 weeks. The severity score was measured at the initial evaluation, and the patients were followed up at 2-week intervals for 8 weeks. A global evaluation of improvement was done at 8 weeks. RESULTS: Thirty-eight patients completed the study; 21 patients in the metronidazole group and 17 patients in the placebo group could be evaluated. There was a statistically significant decrease of the mean score even at week 2; the difference became highly significant at 8 weeks (p < 0.001). On the final evaluation at 8 weeks, 14 patients in the metronidazole group showed marked improvement to complete clearance as compared to only 2 patients having moderate improvement in the placebo group (p < 0.001). CONCLUSION: The present trial has demonstrated the effectiveness of topical 1% metronidazole gel in seborrheic dermatitis.     

A randomized, double-blinded, placebo-controlled trial of pseudocatalase cream and narrowband ultraviolet B in the treatment of vitiligo

Background  Pseudocatalase cream in conjunction with narrowband ultraviolet B (NB-UVB) has previously been reported to result in repigmentation of vitiliginous skin.
Objectives  The purpose of this 24-week, double-blind, placebo-controlled, randomized, single-centre trial was to assess the efficacy of pseudocatalase cream and NB-UVB vs. placebo and NB-UVB for the treatment of vitiligo.
Methods  Patients with active vitiligo on their face and/or hands applied either pseudocatalase cream or placebo to their whole body, twice daily for 24 weeks. NB-UVB therapy was administered three times a week for the duration of the trial. Efficacy was assessed primarily by digital image analysis of photographs.
Results  Thirty-two patients were randomized to either the pseudocatalase arm ( n  =   14) or placebo ( n  =   18). Between-group analysis did not show a statistically significant improvement in percentage area affected in the pseudocatalase cream group when compared with placebo. However, a statistically significant improvement was found within each group by week 12, which was maintained throughout the study.
Conclusions  NB-UVB treatment is a moderately effective treatment for vitiligo. Pseudocatalase cream does not appear to add any incremental benefit to NB-UVB alone.     

Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study

The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with seborrhoeic dermatitis were enrolled. Cases were randomly treated with metronidazole 0.75% gel or placebo for four weeks and were additionally followed up for another four weeks. Patients were evaluated by scoring before the treatment, once a week during the treatment and twice after the cessation of the treatment within a 15-day interval. Furthermore, patient satisfaction and doctor global evaluation were done at the end of the treatment and of the study as well. In the metronidazole group 33 patients (median age: 26, total severity score: 15.0 +/- 11.0 (median +/- interquartile range) and in the placebo group 34 patients (median age: 26, total severity score: 13.0 +/- 7.5) were enrolled in the study. Three patients from the metronidazole group and four patients from the placebo group did not attend to follow-up visits. Erythema, scales, papule, pruritus and the total severity scores in both group decreased significantly during the treatment when compared with the basal levels (p < 0.05). There was no difference between the two groups in terms of efficacy (p > 0.05). Total severity scores were found as 7.33 +/- 1.08 and 6.43 +/- 0.93 in the metronidazole and placebo groups at the end of the treatment, respectively. After the cessation of the treatment, all scores had increased rapidly. Total severity scores were 10.40 +/- 1.54 and 11.20 +/- 1.53 in the metronidazole and placebo groups one month after the cessation of the treatment, respectively. Both metronidazole 0.75% gel and the placebo were well tolerated by the patients. In conclusion, in the treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is well tolerated but it is only as effective as placebo and the disease severity quickly returns to the basal levels after the cessation of treatment.     

Comparative study of some treatment modalities of rosacea

Background   Rosacea is a disease of complex pathogenesis and variable response to various therapeutic methods.
Aim of the work   To evaluate and compare the efficacy, safety and side effects of some topical lines of treatment of rosacea.
Patients and methods   The study included 24 patients (23 females and 1 male) with rosacea on the face. They were classified into three groups – each including eight patients (16 face sides) – and treated with one of three topical agents (azelaic acid 20% cream, metronidazole 0.75% cream or permethrin 5% cream) on one side of the face and another one on the other side twice daily for 15 weeks.
Results   There was a significant improvement of lesions after 15 weeks of topical treatment with the three agents. Azelaic acid cream was significantly more effective on inflammatory lesions but not erythema than the other two creams. Side effects – mostly transient – were observed with topical creams with no significant difference. They included itching, burning sensation, oedema and scales. Patients who used azelaic acid 20% cream were more satisfied than with other modalities.
Conclusion   Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream or permethrin 5% cream with the added benefit of increased patient satisfaction.     

Management of Female Genital Warts with an Analog of Imiquimod 2% in Cream: A Randomized,Double-Blind,Placebo-Controlled Study

The purpose of this randomized, double-blind, placebo-controlled study was to determine the clinical efficacy and tolerability of an analog of imiquimod (2%) in cream to cure genital warts in women. Sixty preselected women, ranging between 18 and 45 years of age (mean 24.3) and having 411 lesions (mean 6.8) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient received a precoded 40-g tube and instructions on how to apply the trial medication to their lesions at home two times daily for five consecutive days per week. The active treatment period was six weeks. Patients were evaluated on a weekly basis. A clinically and PCR established total clearance of target warts was recorded as a cure. By the end of the treatment, 43.3% of patients and 42.8% of warts were cured. Code disclosure revealed that imiquimod cream had cured 83.3% of the treated patients and 84.3% of the treated warts, while the placebo healed one subject and four warts (p<0.0001). Eight patients (13.3%) in the imiquimod group experienced mild to moderate, non-objective, drug-induced symptoms with no dropouts. Among the 26 cured patients, five had a relapse after 11 months. In conclusion, the data presented demonstrate that 2% imiquimod in cream with mild to moderate subjective side effects is significantly more effective than placebo in eliminating genital warts in women.