Efficacy of Combining Topical Antibiotic/Steroid/Moisturizer Therapy Compared to Active Comparator in Atopic Dermatitis.

Study Overview
=================
Brief Summary
-----------------
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that occurs most commonly during early infancy and childhood. It is frequently associated with abnormalities in skin barrier function, allergen sensitization and recurrent skin infections. AD is a major public health problem worldwide, with prevalence in children of 10-20% and 2-5% of the general population. The skin of AD patients is susceptible to colonization and infection with Staphylococcus aureus (SA )which contribute significantly to the severity of the clinical manifestations of eczema, triggering a vicious cycle. Fusidic Acid (FA) cream is a topical antibiotic widely used in the treatment of skin and soft tissue infections and infected atopic dermatitis. However in recent years, the emergence of drug-resistant organisms, e.g. Methicillin- resistant Staphylococcus aureus (MRSA) has led to scrutiny of antibiotic use. Prolonged use of topical FA has been linked with emergence of FA-resistant Staphylococcus aureus (FRSA) . Fusidic acid is a natural antibiotic, extracted from cultures of Fusidium coccineum, which has a powerful antibacterial action. Topical use of Fusidic acid is fully in line with therapeutic strategies that recommend the use of an antibiotic with the narrowest activity spectrum to minimize the risk of resistance. In AD with infected lesions, combined treatment with antibiotic and steroid demonstrates greater efficacy over the use of steroid. Trial Design: A three-center, double blind, randomized ,phase II , parallel group, efficacy trial. Type of Intervention: A triple compounded cream containing a topical antibiotic , topical steroid and moisturizer. Type of control: Active control containing a double compounded cream comprising a topical steroid and moisturizer . Study population and Setting: A sample of 78 subjects will be recruited from Red Cross Children's Hospital , Nelson Mandela Academic Hospital and King Edward Hospital Estimated duration of trial: 12 months. Duration of participation: Each subject will participate in the trial for a maximum of 140 days. Primary endpoint: reduction in SCORAD scores; frequency of clinical flares for AD and improvement in the quality of life at 140 days. The benefit of this trial is that it provides a simple and effective approach to the management of atopic eczema.

Official Title
-----------------
A Multicentre Study Evaluating the Efficacy of Combining Topical Antibiotic/Steroid/Moisturizer Therapy Compared to Standard of Care in the Treatment of Severe Atopic Dermatitis, a Phase II Randomized, Clinical Trial

Conditions
-----------------
Severe Atopic Dermatitis

Intervention / Treatment
-----------------
* Other: Polyethylene glycol hexadecyl ether & Betamethasone valerate cream 0.1%
* Other: Fusidic acid, polyethylene glycol hexadecyl ether & Betamethasone valerate cream 0.1%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must have a parent/legally authorized representative, who is able to give informed consent and willing and able to comply with all the required study procedures. Assent is required from children who in the investigator's judgement, are capable of understanding the nature of the study. Participants must have have AD as defined by the UK Working Party Criteria Participants can be female or male, older than 2 years but younger than 10 years (up to their 10th birthday) Participants must not be on systemic antibiotics treatment at recruitment Participants must have a baseline SCORAD score of 50 or above (severe AD) Participants must be eligible for second line treatment agents for AD (systemic or photo therapy) Exclusion Criteria: Participants must not be systemic agents (e.g. immunosuppressive) for AD Participants must not be younger than 2 years or over 10 years in age. Participants must not be using g bleach baths as a staphylococcus eradication measure at the time of enrollment, Participants must not have mild-moderate AD (SCORAD< 50) Participants must not be immune-compromised with AD Participants must not be on photo therapy for AD Participants must not be using wet wrap therapy for AD

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fusidic acid, polyethylene glycol hexadecyl ether & Betamethasone valerate cream 0.1%
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group R<br>Polyethylene glycol hexadecyl ether & betamethasone valerate cream 0.1% . ( 4 applications per day for 14 days treatment to taper fortnightly) | Other: Polyethylene glycol hexadecyl ether & Betamethasone valerate cream 0.1%<br>* Polyethylene glycol hexadecyl ether -Moisturizer. Betamethasone valerate cream 0.1% -Topical steroid<br>* Other names: Lenovate cream, 15g, Reg No. 27/13.4.1/0493;|
| Experimental: Group A<br>Fusidic acid & Polyethylene glycol hexadecyl ether,& betamethasone valerate cream 0.1%). ( 4 applications per day for 14 days treatment to taper fortnightly) | Other: Fusidic acid, polyethylene glycol hexadecyl ether & Betamethasone valerate cream 0.1%<br>* Polyethylene glycol hexadecyl ether -Moisturizer. Betamethasone valerate cream 0.1% -Topical steroid Fusidic Acid - Topical Antibiotic<br>* Other names: Fusidic Acid (Fucidin cream), 15 g, Reg No. Q/20.1.6/128;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCORAD scores | Reduction of SCORAD scores in the treatment group (A) of patients comparing with scores in the control group (R), at the end of the study with reference to baseline | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infants Dermatitis' Quality of Life (IDQOL) index | Improvement in the Infants Dermatitis' Quality of Life (IDQOL) index in group (A) patients compared to that of the control group (R) at the end of the study compared to baseline | 20 weeks | 
| Frequency of AD relapse episodes | Comparison of the frequency of AD relapse episodes in group (A) patients compared to the frequency of relapse episodes in control group (R) patients. | 20 Weeks | 
| Time to AD Relapse | Comparison of the time to AD relapse episodes in group (A) patients compared to the time to relapse episodes in control group (R) patients. | 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eczema, Topical Antibiotics, Fusidic Acid, Atopic Dermatitis