A randomized, double-blind, controlled trial of amorolfine 0.25% cream versus sertaconazole 2% cream in limited variety of tinea cruris/ corporis.

Dermatophytoses, thecommonest fungal infections, occur worldwide.Although not lifethreatening, they may produce significant symptoms which interfere with thequality of life. They are par­ticularly widespread in tropical countriesbecause of warm and humid climate, crowded living conditions, and othersocio-economic factors.

Despite the advent of new antifungal agents, the treatment remainschallenging. Many clinical trials have been conducted for the purpose ofsearching better drugs, both in terms of effectiveness and safety.Combinationof terbinafine 1% cream and butenafine1% cream; terbinafine hydrochloride 1% cream vs. sertaconazole nitrate2% cream,  terbinafine hydrochloride 1%cream vs. sertaconazole nitrate 2% cream vs. luliconazole 1%,Whitfield’sointment + oral fluconazole versus topical 1% butenafine are evaluated in thepast. Since amorolfine and sertaconazole have emerged as the newest topicalantifungals in the wide plethora of drugs available for combating thisnotorious dermatosis, the aim of this study is to compare the effectiveness andsafety of amorolfine 0.25% cream versus sertaconazole 2% cream in the treatmentof limited variety of tinea cruris/corporis. To the best of our knowledge, tilldate no study comparing the efficacy and safety of amorolfine 0.25% cream andsertaconazole 2% cream has been done in localized tinea corporis and tineacruris. Our study would alsoevaluate the cost-benefit ratio and cost-utilization ratio with the twotreatment groups.

Our objectives are to evaluate and compare the effectiveness,safety and improvement in quality of life of two arms of the study, viz.amorolfine 0.25% cream versus sertaconazole 2% cream.

All untreated male and non-­pregnant femalepatients above 18 years of age complaining of acute, symptomatic tinea cruris/corporis withlimited involvement i.e. limited to single body region with KOH mount showingpositive results (hyphae) will be included. Pregnantor nurs­ing females, patients with diabetes mellitus, malignancy, renal orhepatic dysfunction, those who have receivedtopical antifungal agents within the past week or received systemic antifungalagents within past four weeks and have a history of hypersensitivity toany of the study drugs will be excluded.

This institution-based, randomized, double blind, parallel group,comparative trial will be carried out in a tertiary care hospital of easternIndia. Every patient will be given treatment for 4 weeks and followed up till 6thweek. Follow-up will be scheduled at two weekely intervals.

The sample size is 30 tinea corporis/cruris patients in eachtreatment group. This was calculated considering mycological cure of 78.9% withamorolfine cream and 100% with sertaconazole cream, with 80% power and 0.05probability of Type 1 error, for this parameter. Considering a 10% possibledropout rate, this translated to a recruitment target of approximately 33subjects per group or 66 subjects overall.

Eligible patients will be randomized into either group A(amorolfine0.25% cream) or group B (sertaconazole 2% cream) with allocationratio 1:1 as per the randomization sequence. Allocation concealment will bedone by sequentially numbered opaque sealed envelope (SNOSE) technique.

After thorough evaluation and collection of skin scraping; theinvestigator will refer patient to Independent Co-ordinator (IC) who willassign treatment to patients.. The tubes will be painted in opaque white color,kept in an opaque envelope and coded “medication A†and “medication B†by theIC. IC will be responsible for the dispensing the medications as perrandomization. Thus both patient and assessor will be blind to the treatmentreceived. . The statistical analysis will be performed by an individual whowill be blinded to the treatment arms and would identify the treatment receivedby the patients in terms of code (group A or group B).

Studyprocedure:

After obtaining written informed consent form each patient,screening will be done. At screening, patients’ demographic details (age, sex,weight, and height) and detailed medical history (including history ofhypersensitivity, other systemic diseases, concomitant medication and previoustreatment) will be recorded. Physical examination will include localization,clinical classification and recording of the affected area. Specimens will betaken from the lesion for KOH (potassium hydroxide) 10% wet mount and cultureon Sabouraud’s dextrose agar (SDA). Blood will be collected for hematology,biochemical analysis (urea, creatinine, LFT).

Patients in group A will receive amorolfine 0.25% cream twicedaily application to the lesions along with oral cetirizine 10 mg once daily atbedtime for 4 weeks. Patients in group B will receive sertaconazole 2% creamtwice daily application to the lesions along with oral cetirizine 10 mg oncedaily at bedtime for 4 weeks. After screening and baseline visit patients inboth groups will be followed up at 2nd, 4th and 6thweek for efficacy and safety parameters.

Study end points:

Efficacy end points

Primaryefficacy end point:

• Clinical cure at 2nd week, 4th week and 6th week.
• Mycological cure at 4th week and 6th week and will be defined as negative KOH microscopy and negative culture.
• Global cure (combined mycological and clinical cure). Patients will be classified as cured for this combined variable only if they are mycologically and clinically clear. All other cases will be classified as failures for this particular variable.

Secondaryefficacy end point: Assessed ateach follow up visit

·        Investigatorwill clinically assess the lesion and will grade the Clinical improvement  asfollows:

o   Grade 0 (Clinical Failure):No improvement.

o   Grade I: Persistence of few papular lesions or erythema with mildto moderate itching.

o   Grade II: Scaly lesions with or without itching.

o   Grade III (Clinical cure):Disappearance of original lesions with or without residual pigmentation

.Safety end points

·        Spontaneouslyreported adverse events and those elicited by the clinician  at each follow up

·        Routinelaboratory investigations: Routine hemogram, random blood sugar, urea,creatinine, liver function tests (LFT). (at baseline and week 4 visit)

Global assessment of safety and efficacy

At the end of treatment and test of cure (week 4), patients aswell as the investigator will assess treatment for safety as well as efficacyon the Likert’s five point scale as- poor, fair, good, very good, excellent.

Compliance

The compliance will be assessed by daily diary provided to thepatients.

Quality of life

Health outcome will be assessed by using vernacular version ofDermatology Life Quality Index (DLQI) after taking permission from thedeveloper.

Cost per patient cured

To calculate this, cost for acquisition of drugs will beconsidered.

Other variable

Photograph of target lesion at baseline and each follow up visit.