Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05881980 |
| Other study ID # |
ERC-DMC/ECC/2023/81 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
May 2023 |
| Est. completion date |
November 2023 |
Study information
| Verified date |
May 2023 |
| Source |
Dhaka Medical College |
| Contact |
Dr. Afsana Nahid |
| Phone |
01716908871 |
| Email |
afsanaderma[@]dmc.gov.bd |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is a rise in the prevalence in recent years especially in tropical countries along with
an increase in the number of treatment failures with chronic and recurrent dermatophytosis.
There is a huge gap between the treatment required in the present scenario and the treatment
guidelines given in the standard books. The aim of the study is to determine the
effectiveness of terbinafine and itraconazole in different doses and in combination in the
treatment of dermatophytosis. The study design will be a randomized parallel-group trial.
Patients will be randomly divided into five parallel arms in which two of the standard drugs
in recommended doses will be compared with their double doses and with a combination of both
drugs. The patients will be reevaluated at 2, 4, 6, and 8 weeks of treatment (the end of
therapy), using the physician Global Assessment (PGA) Scale. The cure will be considered a
complete clinical resolution of the lesions. The patient's response to the treatment will be
recorded. Safety and patient compliance will be recorded at each follow-up visit. Findings of
observation will be recorded on a pre-prescribed and pre-tested data collection form. After
collection, all data will be checked and compiled. Data will be processed and analyzed using
computer software with statistical packages for social science SPSS-26. An analysis plan will
be developed keeping in view the objectives of the study. The results of the continuous
measurement will be presented on mean ± SD (mean-max) and results on categorical measurements
will be presented in numbers (%). A p<0.05 will be considered statistically significant.
Results will be disseminated to all Dermatology departments in Bangladesh.
Description:
Dermatophyte infections are common fungal infections aggravated by hot and humid climates.
Unprecedented changes in the epidemiology, clinical features, and treatment responsiveness of
dermatophyte infections have been noted in the recent past in Bangladesh, with many patients
presenting with treatment failure and chronic relapsing tinea. Terbinafine and itraconazole
are commonly used oral antifungal agents for the same. There is a paucity of original studies
especially in Bangladesh depicting dermatophytosis becoming a huge menace both to the patient
and to the treating physician. Terbinafine is a fungicidal drug and acts by inhibiting the
enzyme squalene epoxidase which converts squalene to lanosterol. Itraconazole is basically a
fungistatic drug that acts through the inhibition of the enzyme 14α-demethylase. Many
dermatologists have started using higher doses and combination regimens of antifungals to
counter this problem. However, such regimens have not been validated. Therefore, this study
is designed to evaluate the efficacy of terbinafine and itraconazole in conventional and
increased dosages and in combination in the treatment of tinea corporis, tinea cruris, and
tinea faciei.
Objectives:
1. General: To evaluate the efficacy and safety of terbinafine and itraconazole in
conventional and increased doses and in combination with dermatophytosis patients
attending the outpatient department of Dermatology and Venereology in Dhaka Medical
College Hospital.
2. Specific:
- To evaluate the efficacy and safety of terbinafine in conventional and increased
doses in dermatophytosis patients attending at the outpatient department of
Dermatology and Venereology in Dhaka Medical College Hospital.
- To evaluate the efficacy and safety of itraconazole in conventional and increased
doses in dermatophytosis patients attending at the outpatient department of
Dermatology and Venereology in Dhaka Medical College Hospital.
- To evaluate the efficacy and safety of terbinafine and itraconazole in combination
with dermatophytosis patients attending at the outpatient department of Dermatology
and Venereology in Dhaka Medical College Hospital.
- To observe the side effects of terbinafine and itraconazole in conventional and
increased doses and in combination with dermatophytosis patients attending at the
outpatient department of Dermatology and Venereology in Dhaka Medical College
Hospital.
Methodology:
Study design: Randomized parallel-group trial. Place of study: Department of Dermatology and
Venereology, Dhaka Medical College Hospital (DMCH), Dhaka Period of study: The study will be
conducted over a period of six months from the approval of the protocol.
Study population: The dermatophytosis patients attending the outdoor Dermatology &Venereology
department, Dhaka Medical College Hospital within the study period.
Sampling method: Simple Random sampling
Ethical Consideration:
Approval for the study will be obtained from the Ethical review committee of Dhaka medical
college, Dhaka prior to the commencement of the study. The purpose of the study and its
procedure, potential risks, and benefits will be explained to the patients in an easily
understandable local language. All participating subjects will be assured that they would
have the full right to withdraw themselves from the study at any time for any reason
whatsoever and their refusal to participate or withdrawal from the study would not hamper
their treatment anyway. They will also be assured that all records provided by them would be
kept confidential and would not be disclosed anyway except for the purpose of the study. Then
informed consent will be sought from them and the patients who will voluntarily consent to
participate in the study will only be included.
Sample size:
The sample size is calculated using the following formula P1 = 90 (proportion of the outcome
variable of the present study) P2 = 50 (known proportion of a historical control) α = 0.05 in
5% level of significance β= 0.1 in 90% power where f (α,β) is a function of α and β, the
values of which is 10.5 so, n=22.3 So, a desired sample size of 25 patients in each group was
calculated considering cure rates of 50% (based on current data on the effectiveness of
itraconazole in India) and 90% (proportion of the outcome variable of the present study for
combination therapy of terbinafine with itraconazole), with a type I error rate of 0.05, a
type II error rate of 0.1. By taking 1:1 allocation and considering the dropout rates to be
20%, the final sample size calculated is 150.
Variables to be studied:
1. Socio-Demographic variables:
- Age
- Sex
- Marital status
- Occupation
- Residence
- Religion
- Family history
2. Clinical variables:
- Sites involved
- Global improvement grade- grade I (1-25%), grade II (26-50%), grade III (51-75%),
and grade IV (76-100%)11
- Types - tinea corporis, tinea cruris and tinea faciei
3. Laboratory variables:
- CBC,
- LFT,
- RFT,
- KOH microscopy and
- ECG
Operational definitions:
Dermatophytosis: Dermatophytosis is a superficial infection caused by a group of fungi,
dermatophytes. The infection is common worldwide with higher prevalence in tropical
countries.
Tinea corporis: Tinea corporis refers to any dermatophytosis of glabrous skin except palms,
soles, and the groin.
Tinea cruris: Tinea cruris is a dermatophytosis of the groin, genitalia, pubic area, and
perineal and perianal skin.
Tinea faciei: Tinea faciei is a dermatophytosis of the face. BSA: Body surface area (BSA)
involvement will be calculated using the ' Rule of palm '. The total palmar surface of the
palm and the five digits of the patient were together taken equivalent to 1%28.
PGA: The physician's global improvement(PGA) scale: The global improvement will be graded as
grade I (1-25%), grade II (26-50%), grade III (51-75%), and grade IV (76-100%) improvement in
overall clinical symptoms at the end of therapy.10 Efficacy: In medicine efficacy can be
defined as, the ability of an intervention (a drug or surgery) to produce the desired
beneficial effect.
Safety: Drug safety refers to the frequency of treatment-emergent adverse drug effects (i.e.
physical or laboratory toxicity) that could possibly be related to the drug. They emerge
during treatment and were not present before treatment, or they become worse during treatment
compared with the pretreatment state.
Study procedure:
Participants selection: One hundred and fifty patients fulfilling the selection criteria will
be randomly allocated to five parallel treatment groups on the basis of lottery and each
group will contain 30 patients (allocation ratio 1: 1: 1: 1:1). Allocation will be concealed
using sequentially numbered, sealed, opaque envelopes, which will contain the allocation code
written on folded paper; the envelopes will be opened after enrolment of the patients. Both
random sequence generation and allocation concealment will be done by a person unrelated to
the trial. Skin scrapings will be taken at enrolment.
Consent and recruitment: Witnessed, written and informed consent will be taken by the
patients. All female patients of childbearing age will be advised to avoid pregnancy during
treatment. The patient will be evaluated on the basis of history and clinical findings and
the diagnosis will subsequently be confirmed by KOH examination.
Baseline information: Socio-demographic characteristics will be assessed in terms of gender,
age, religion, occupation, marital status, and place of residence. Participants will also be
asked about the history of dermatophytosis among family members. Details of involved sites at
the presentation and clinical course of the lesions will be registered. Clinical examination
will be performed based on visual inspection and palpation. Data on location, size, clinical
presentation of the lesions, and the clinical course will be recorded. Skin lesions will be
encountered during the survey and will be photographed using a digital camera on every visit.
The following data will be recorded for each patient: body surface area affected, treatment
given, microscopy results, and investigations at baseline.
Patients will be evaluated for the severity of clinical parameters namely itching, erythema,
and scaling using the four-point scale: 0 = none, l = mild, 2 = moderate, and 3 = severe. The
most severe lesion will be identified as the index lesion, from which scraping and KOH
microscopy will be performed at baseline and then at follow-up visits. The investigations
will be performed at baseline are LFT and ECG for itraconazole groups and LFT and CBC in the
terbinafine group. RFT will be done for all the groups. In combination, CBC, LFT, RFT, and
ECG will be done.
Global assessment: Patients will be evaluated for the severity of clinical parameters namely
itching, erythema, and scaling using the four-point scale: 0 = none, l = mild, 2 = moderate,
and 3 = severe. All the patients will be followed at baseline, 2 weeks, 4, 6, and 8 weeks
with repeat KOH examination from the same site, wherever necessary. The global improvement
will be graded as grade I (1-25%), grade II (26-50%), grade III (51-75%), and grade IV
(76-100%) improvement in overall clinical symptoms at the end of therapy.
Confidentiality: In this study, privacy, anonymity, and confidentiality of data information
identifying any patient will be maintained strictly. Data taken from the participants will be
coded and regarded as confidential and will be kept locked under the investigator for
purposeful use only.
Participant timeline: six months.
Intervention: Five parallel study groups will be as follows:
1. Terbinafine 250 mg/day: T 1
2. Itraconazole 200 mg/day: I 1
3. Terbinafine 250 mg + Itraconazole 200 mg/day: T + I
4. Terbinafine 500 mg/day in two divided doses: T 2
5. Itraconazole 400 mg/day in two divided doses: I 2
Systemic drugs:
Patients will be prescribed the allocated antifungal drug. The same brand of drugs will be
given to all the patients to rule out inter-brand variability in the efficacy of treatment.
Patients will receive antihistamines (fexofenadine 180 mg). Patients will be asked to bring
used strips of medicines and those in use at each visit. They will be reminded to take the
medicines as prescribed at each visit and receive the treatment for 2 weeks. Patients will be
advised against using any other treatment.
Topical therapy: Topical antifungals will not be prescribed. Emollient will be given to all
participants.
Adherence: Adherence will be recorded in a treatment diary, which will act as an aide memoir
to inform hospital appointments. Additional training will be provided at the hospital visit
if it is noticed the participant will misunderstand the treatment schedule.
Follow-up: The enrolled patients will be called for follow-up every two weeks for a total of
eight weeks. The following data will be recorded for each patient: body surface area
affected, PGA, treatment given, microscopy results, investigations at baseline and subsequent
follow-ups, and follow-up data. Investigations will be done at every second visit, LFT and
ECG will be repeated in the itraconazole groups, and LFT and CBC in the terbinafine group.
RFT will be done at every second visit for all the groups. In the combination group, LFT,
CBC, and ECG will be repeated at every second visit. The most severe lesion will be
identified as the index lesion, from which scraping and KOH microscopy will be performed at
baseline and then at follow-up visits. Patients who will fail to follow up for two
consecutive visits will be considered as being lost to follow-up and will be treated as
dropouts.
Treatment modification following clinical response or adverse effects:
At the end of 4 weeks, those who will show no or less than 25% clinical improvement (global
improvement grade I) will be labeled as 'complete failures' and will be given alternative
treatment (any treatment from the rest four options); while those with partial clinical
response (global improvement grades II and III) will be asked to continue same treatment for
subsequent 4 weeks. if any side effects occur at any point of the treatment period then
treatment will be continued with the alternate drug.
Data collection and management: Permission will be taken from each volunteer participant by
using a written consent form. After getting consent from the participants, a standard
questionnaire data sheet will be used to collect demographic information. The patients will
be interviewed face to face by the researcher for the purpose of collection of data. All the
individual's study will be subjected to a complete assessment of history and clinical
examination including clinical parameters namely itching, erythema, scaling, and body surface
area involvement.
Safety evaluation: All adverse events (AEs) will be assessed for severity and relationship to
terbinafine and itraconazole at each visit. Multiple occurrences of the same AE will be only
counted once for each patient. Laboratory measurements will also be included for safety
evaluation.
Withdrawal of study participants: Each patient will enjoy every right to participate or
refuse or even withdraw from the study at any point in time.
Storage: Drugs will be stored at room temperature. Prohibited medications: Any intervention
for dermatophytosis, besides those provided in the trial, will be specifically prohibited.
Statistical analysis: A parametric one-way analysis of variance (F test) will be applied to
find out the mean differences among the five treatment groups. The chi-square test will be
used to find out significant differences in the proportions among treatment groups and it
will be also used to test the significance of the change from baseline to various follow-ups
within the groups. The level of significance will be set at 5% and p< 0.05 will be considered
significant. Patients who will be excluded from the study due to adverse events or loss to
follow-up will not be included in the data for statistical analysis.
Quality assurance strategy: In order to ensure the proper quality of the data collection
procedure, firstly a work manual was made. Then a sample size was selected. A standard
questionnaire was made. Then the questionnaire was 16 pretested. The pretest ensures that the
respondents are able to understand the questionnaire and answer accordingly.
Utilization of results: The data generated from this study may be helpful for dermatologists
to evaluate dermatophytosis treatment. Additionally, the findings of the proposed study may
serve as a baseline. Data to undertake further research on a large scale.
Facilities: Resources, equipment, subjects (human), etc. required for the study]: All
facilities are available in Dhaka Medical College Hospital, Dhaka. No additional facilities
will be needed.
Observation and results: The result of the study and statistical analysis will be presented
by tables, figures, graphs, diagrams, charts, photographs, etc. All these should have their
own legends (i.e., title) and be serially numbered.
Discussion: Discussion will be done on the basis of the results obtained from the study.
Conclusion: A conclusion will be drawn depending on the results and discussion.
