英文论文致谢 Double Blind Randomized Controlled Trial

Research Question

Is Lantana camara 17% leaf extract ointment compared to mupirocin 2% ointment in the treatment of impetigo in 7 to 14 days?

Significance of the Study

This study aims to demonstrate the efficacy of topically applied L. camara 17% extract ointment in the treatment of Impetigo as compared to Mupirocin 2% ointment. The topical extract if found effective may be used as an alternative treatment. This plant is common in our local setting and is cost effective.

Objectives

General Objectives

To determine the efficacy of topically applied L. camara 10 % extract ointment as compared to Mupirocin 2% ointment in the treatment of Impetigo.

Specific Objectives

The specific objectives of this study are:

To compare the clinical efficacy of L. camara 17% extract ointment vs the efficacy of Mupirocin 2% ointment in the treatment of Impetigo

To determine the potential adverse reactions from the L. Camara 10% extract ointment

METHODOLOGY

Design and Setting

This is an open label and double blind, randomized controlled trial.

This study will be done at the Outpatient Clinic of the Department of Dermatology at

Davao Medical Center from March 20 to May 30, 2010.

Participants

Patients who will be able to meet the inclusion criteria will be included in the study and randomly allocated to receive either L. camara 17% extract ointment or Mupirocin 2% ointment.

Inclusion Criteria:

Patients with mild to moderate impetigo.

Clinincally diagnosed with mild to moderate impetigo.

Exclusion Criteria:

Those treated with topical or systemic antibiotics within the preceding 48 hrs.

Those with severe impetigo or with evidence of cellulites.

Patients < 1 year old.

Immunocompromised patients

Patients with acute or chronic dermatoses.

Known hypersensitivity to mupirocin or polyethelene glycol ointment.

Preparation of Test Drug

L. camara leaf 15%, 17% leaf extract will be prepared by a local Herbal Research and Processing plant. The leaf extract will be collected and washed with water and dried in an incubator at 50ËšC for 5-7 days. The dried materials will be grinded to powder using a grinder. The dried powder will be extracted using ethanol (100g/1500ml) in a conical flask for 5 days at 37ËšC. Afterwards the solvent will be filtered using a filter funnel and the solvents will be distilled under the reduced pressure in EYELA rotary evaporator until excess solvent is evaporated. The alcoholic extract of L. camara will be mixed with homogeneously with blank Vaseline in the concentration of 10% and kept in fridge at 4ËšC until it is used.

Phase I

A pretesting phase will be done on twenty healthy volunteer subjects to assess if any adverse reactions from the L. camara extract will occur on the twenty healthy subjects, a finn chamber patch test will be utilized. The subjects will apply the L. camara 15%, 17% and 20% extract ointment in each chamber on the upper back. Reading of the test area will be done after 48 hours and 72 hours. Any skin reactions will be evaluated for the presence of erythema, infiltration, papules, papules, discrete vesicles and bullous reactions. The following criteria will be used to score reactions according to standard patch testing guidelines established by the International Contact Dermatitis Research Group. All skin reactions will be scored as: (-) negative; IR irritant reaction; (?) doubtful reaction; (+) weak positive; (++) strong positive reaction; or (+++) extreme positive reaction (Appendix E). The highest percentage of the L. camara ointment with a negative reaction will be used in the study.

Phase II

This phase consists of an open label study of 20 patients clinically diagnosed with impetigo. Clinical diagnosis of impetigo is defined as lesions with honey-colored drainage with crusting on erythematous base. Mild impetigo is described <25 cm2 total surface area of lesions, moderate impetigo has 25-50 cm2 total surface area of lesions and severe is > 50 cm2 total surface of lesions.

All subject’s parents or guardians will receive written and oral information about the objectives of the study and its possible outcomes and adverse reactions written informed consent approved by the Davao Medical Center Ethics Committee will then be obtained from the parents or guardian (Appendix A or B). For children ages 7 to 16 years old an additional”Child patient information and informed consent form” (appendix C or D) will be given.

Baseline demographics, general physical examination and photographed documentation will be done by the investigator. The following data will be recorded in each of the patient’s age, sex, date of enrollment, address and contact number, baseline site(s) of lesions, total measurement and characteristic of lesions. The investigator will evaluate the lesions by grading for exudates/ pus, crusting and erythema are graded on a scale of 0 (absent) to 3 (severe) (Appendix E).

Ten volunteer subjects will be chosen for open trial study for the use of L. camara 17% extract ointment. Subjects will be instructed to wash with non-antibacterial soap and to apply ointment two times daily for 7 days and to continue treatment for another 7 days if lesions is not clinically cured. Adverse reactions such as stinging, dryness and pruritus on a scale ranging from 0 (none) to 3 (severe). Photograph documentation will be done per visit (Appendix E).

Phase III

Phase III will commence found on the efficacy outcome of the Phase II open label study. A statistically significant result in phase II warrants continuation to phase III. In this phase, 130 volunteer subjects will be randomly allocated to either the L. camara 17% extract or Mupirocin 2% ointment group by an assistant reasearcher. The allocation of the medication will not be known to both the subject and the investigator.

Patients will be given the precoded containers containing the L. camara 17% extract ointment or the Mupirocin 2% ointment. They will be instructed to first wash the infected lesion with a non-antibacterial soap provided by the investigator and pat dry with a clean towel and apply the ointment on their lesions twice a day. Patients will be instructed to come back after 7 days of treatment. Participants will be evaluated on the characteristics of the lesions and assessed if clinical cure has been achieved. Clinical cure will be achieved with “0” score of the total score. If patient has not achieved clinical cure patient will be given another container of the same ointment to be applied for 7 days, after which time reassessment will be done. The study will be restricted to 14 days of active treatment. Adverse reactions such as stinging, dryness and pruritus on a scale ranging from 0 (none) to 3 (severe) will be recorded. Photograph documentation will be done per visit (Appendix E).

Randomization and Blinding

The subjects will be randomized to receive either L. camara ointment or mupirocin ointment based on randomization downloaded from www.radonmization.com. They will be given precoded containers with the test or control drug by the research assistant.. Both the investigator and the subjects will not be aware of the assignment of groupings and the ointments and will be used for two times daily for 14 days. Patients are instructed to refrain from showing the container or talk to other subjects or the investigator about treatment applied. The assigned precoded container will be good for one week’s use, at which time patient will be given another container for another week until the end of treatment.

Outcome Measures

Main outcome measures will be evaluated as clinical cure and failure response. The definition for clinical cure is 100% or complete absence of erythema, crusting or exudation of lesions. Failure response is defined as presence of any of the following: erythema, crusting or exudation of lesions.

Sample size computation

The sample size was computed based on the following formula ( Lemeshow,et al textbook).9

n = Z1-α2 2P(1-P) + Z1-β P1 (1- P1) + P2 (1- P2) 2

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64 subjects per group

Data Handling and Analysis

T-test will be used to compare the efficacy of L. camara l7% leaf extract ointment vs Mupirocin 2% ointment in treating patients with moderate impetigo after 14 days.

Ethical Considerations

The research paper will be reviewed and approved by the Research and Ethics Committee of the hospital. Prior to the research all subject’s parents or guardians will receive written and oral information about the objectives of the study and its possible outcomes and adverse reactions. Written informed consent approved by the Davao Medical Center Ethics Committee will then be obtained from the parents or guardian. Two witnesses will be required to reaffirm the informed consent and will be held at the OPD Davao Medical Center, Dermatology Department (Appendix A or B). For children ages 7 to 16 years old an additional “Child patient information and informed consent form” will be given (appendix C or D).

Travel allowance will be provided upon each visit for both the subject and parent/guardian. They will be asked to note the adverse reactions such stinging, dryness and pruritus and immediately visit the investigator to evaluate. If severe adverse reactions are noticed ongoing medications will be stopped and treated accordingly. The deferred subjects will still be considered part of the study. Free medications will be provided at the end of the clinical trial to patients considered to be treatment failures.

All participants will be notified for follow up visit at the end of the study and will be informed with the study results. All gathered data written will be secured in Davao Medical Center OPD, Dermatology Department for five years. DMC dermatology staff will be given access to the study.

Funds of the study will be provided by the Philippine Dermatology Society