<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03814343</url>
  </required_header>
  <id_info>
    <org_study_id>799/2018</org_study_id>
    <nct_id>NCT03814343</nct_id>
  </id_info>
  <brief_title>Topical Amphotericin B in 30% Dimethylsulphoxide in Treating of Non-dermatophytes Onychomycosis</brief_title>
  <acronym>amphotericin</acronym>
  <official_title>Comparison of Effectiveness of Topical Amphotericin B in 30% Dimethylsulphoxide and 30% Dimethylsulphoxide in Treating of Non-dermatophytes Onychomycosis: Randomized Double Blind Controlled Trial Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mahidol University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mahidol University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The randomized control trial study aimed to evaluate effectiveness and safety of amphotericin&#xD;
      B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Onychomycosis caused by non-dermatophyte molds (NDMs) have become more common in&#xD;
      clinical practice, particularly in tropical and subtropical area. With worldwide prevalence&#xD;
      as high as 10-24% for nail infection, more recent studies have focused on the treatment&#xD;
      regimens for NDMs onychomycosis, especially of Neoscytalidium spp and Fusarium spp. etiology.&#xD;
      However, there has been no consensus to-date regarding standard treatment of choice for NDMs&#xD;
      onychomycosis.&#xD;
&#xD;
      NDMs onychomycosis was considered to be recalcitrant infection. Previous in vitro study in&#xD;
      Malaysia reported high susceptibility of Neoscytalidium dimidiatum in amphotericin B,&#xD;
      voriconazole, and miconazole treatment.Different therapeutic approaches such as oral&#xD;
      antifungal agents, keratolytic agents, combined oral antifungal agents with keratolytic&#xD;
      agents, or surgical nail avulsion, have been implemented but none has been considered a gold&#xD;
      standard protocol in NDMs onychomycosis.&#xD;
&#xD;
      Amphotericin B is the polyene class of antimicrobial compounds. Its properties are fungicidal&#xD;
      and have a broad spectrum with a low rate of resistance. In in vitro study, amphotericin B&#xD;
      was reported to have better efficacy of treating N. dimidiatum infection followed by&#xD;
      terbinafine and voricanazole. The mechanism of action is the interaction with ergosterol of&#xD;
      fungi membrane resulting in forming permeable channels in cellular membrane of targeted&#xD;
      fungi. This causes impairing membrane barrier function. In addition, it also causes growth&#xD;
      inhibition. Amphotericin B is often used in treating disseminated fungal infection and&#xD;
      visceral leishmaniasis. However, Amphotericin B can cause several side effects including&#xD;
      nephrotocixicity, fever, chills, nausea, vomiting, headache, anemia, electrolytes imbalance&#xD;
      (hypokalemia and hypomagnesaemia). Oral amphotercin B has poor bioavailability. Topical forms&#xD;
      are not commonly used due to its highly lipophilic property. As a consequence, topical&#xD;
      amphotericin B is not well absorbed through mucosa or skin resulting in low efficacy. High&#xD;
      dose of topical amphotericin B had been developed but the results didn't work well because it&#xD;
      caused severe adverse events such as blistering, itching, redness, peeling or severe&#xD;
      irritation of the skin and did not even achieve the goal of treatment.&#xD;
&#xD;
      Dimethylsulphoxide (DMSO) is a promising vehicle to enhance the penetration of the drugs to&#xD;
      animal or human skin. In addition, DMSO also has fungicidal activity. In vitro release study&#xD;
      of amphotericin B from amphotericin B in 30% DMSO solution conducted in Siriraj Hospital&#xD;
      revealed adequate amphotericin B concentration in the nails.&#xD;
&#xD;
      Since skin and nail infections caused by NDMs especially N. dimidiatum has been diagnosed in&#xD;
      many countries with the majority cases being reported from Thailand, it could be implied that&#xD;
      N. dimidiatum was endemic pathogens in this area. Published data on treatment regimens of&#xD;
      NDMs nail infection using amphotericin B are still limited. According to the high antifungal&#xD;
      property and low rate of drug resistance of amphotericin B, this randomized control trial&#xD;
      study aimed to evaluate effectiveness and safety of amphotericin B in 30% DMSO solution&#xD;
      comparing with 30% DMSO solution.&#xD;
&#xD;
      Objectives&#xD;
&#xD;
        1. To evaluate effectiveness including mycological cure of amphotericin B in 30% DMSO&#xD;
           solution comparing with 30% DMSO solution in NDMs onychomycosis treatment&#xD;
&#xD;
        2. To evaluate safety of amphotericin B in 30% DMSO solution comparing with 30% DMSO&#xD;
           solution in NDMs onychomycosis treatment&#xD;
&#xD;
      Material and Methods Patients Since there was no previous study that compared amphotericin B&#xD;
      in 30% DMSO with pure 30% DMSO in treating of NDMs onychomycosis, this study designated a&#xD;
      total of 20 patients into two groups as 10 patients with NDMs onychomycosis treated with 30%&#xD;
      DMSO (control group) and another 10 Patients with NDMs onychomycosis treated with&#xD;
      amphotericin B in 30% DMSO. NDMs onychomycosis was diagnosed with diagnostic criteria for NDM&#xD;
      onychomycosis proposed by Gupta et al. Patients with any systemic or topical antifungal&#xD;
      agents at least 3 months prior to the study were excluded from this study.&#xD;
&#xD;
      Design of medication Drugs were prepared in two solutions. First, amphotericin B (Alpharma,&#xD;
      Denmark) was mixed with 30% DMSO (Sigma- Aldrich, Buchs, Switzerland) in 50:50 ratio. A final&#xD;
      concentration of amphotericin B was 2 mg/ml. Later solution was pure 30% DMSO without&#xD;
      amphotericin B. Those two final solutions had the same appearance, odor and texture. The&#xD;
      solution will be kept in amber glass bottles with aluminum foil together with dropper. The&#xD;
      drug regimen is to apply 1-3 drops of the solution once a day to each affected nail and&#xD;
      briefly let the solution evaporate before continuing their usual activities.&#xD;
&#xD;
      Treatment, Follow-up and measurement A randomized control trial study conducted in outpatient&#xD;
      nail clinic, Siriraj Hospital. Patients will be divided into two groups by mixed block of&#xD;
      randomization. First groups will be treated with amphotericin B in 30% DMSO solution. Another&#xD;
      group will be given only 30% DMSO solution. Each patient is subjected to continuously apply&#xD;
      his/ her own drugs followed instruction given for 12 weeks. They will be followed up at 12&#xD;
      weeks, 24 weeks and 36 weeks for re-evaluation of clinical, mycological laboratories,&#xD;
      adherence to the drug and adverse events. Effectiveness was evaluated by clinical improvement&#xD;
      and mycological cure as well as median time to mycological cure. Clinical evaluation would be&#xD;
      assessed by two treatment-blind dermatologists. Regarding mycological cure, it was defined as&#xD;
      negative KOH and fungal culture. Data were analyzed using PASW Statistics version 18 (SPSS,&#xD;
      Inc., Chicago, IL, USA).&#xD;
&#xD;
      Duration of study: 1 year&#xD;
&#xD;
      Study design: Randomized double blind control trial&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Actual">November 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 15, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized double blind controlled trial pilot study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind controlled trial between participants, drug preparing team, doctors, investigators, and outcome assessors.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Effectiveness of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment</measure>
    <time_frame>36 weeks</time_frame>
    <description>Effectiveness was evaluated by patients who had negative on mycological laboratory (mycological cure) as percentage.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Median time to mycological cure of patients with amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment</measure>
    <time_frame>36 weeks</time_frame>
    <description>Median time to mycological cure were defined as time (days, months or years) that had negative on mycological laboratory</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical cure of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment</measure>
    <time_frame>36 weeks</time_frame>
    <description>Clinical cure was defined as the patients had complete clinical improvement or having &lt;10% nail involvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median time to clinical cure of patients with amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment</measure>
    <time_frame>36 weeks</time_frame>
    <description>Median time to clinical cure were defined as time (days, months or years) that had clinical improvement of the affected nails.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate side effects of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment</measure>
    <time_frame>12 weeks</time_frame>
    <description>Side effects was assessed by the percentage of patients developed any side effect such as erythema, burning sensation, pain.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Fungal Infection</condition>
  <condition>Onychomycosis</condition>
  <condition>Fungus, Nail</condition>
  <arm_group>
    <arm_group_label>Active comparator</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10 patients with NDMs onychomycosis treated with amphotericin B in 30% DMSO.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>10 patients with NDMs onychomycosis treated with 30% DMSO.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>amphotericin B in 30% DMSO</intervention_name>
    <description>amphotericin B in 30% DMSO was given to patients in active comparators group for continuous 12 weeks.</description>
    <arm_group_label>Active comparator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>30% DMSO</intervention_name>
    <description>30% DMSO was given to patients in placebo comparators group for continuous 12 weeks.</description>
    <arm_group_label>control comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with non-dermatophyte onychomycosis.&#xD;
&#xD;
          2. Patients aged more than 18 years.&#xD;
&#xD;
          3. Patients has not been treated with any oral/ IV/ topical antifungal therapy within 36&#xD;
             weeks before enrolled.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients had concomitant nail diseases.&#xD;
&#xD;
          2. Immunocompromised host.&#xD;
&#xD;
          3. Patients with dermatophyte onychomycosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sumanas Bunyaratavej, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mahidol University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Charussri Leeyaphan, MD</last_name>
    <role>Study Director</role>
    <affiliation>Mahidol University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Dermatology Siriraj Hospital</name>
      <address>
        <city>Bangkoknoi</city>
        <state>Bangkok</state>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Butani D, Yewale C, Misra A. Amphotericin B topical microemulsion: formulation, characterization and evaluation. Colloids Surf B Biointerfaces. 2014 Apr 1;116:351-8. doi: 10.1016/j.colsurfb.2014.01.014. Epub 2014 Jan 19.</citation>
    <PMID>24521698</PMID>
  </reference>
  <results_reference>
    <citation>Downs AM, Lear JT, Archer CB. Scytalidium hyalinum onychomycosis successfully treated with 5% amorolfine nail lacquer. Br J Dermatol. 1999 Mar;140(3):555. doi: 10.1046/j.1365-2133.1999.02739.x. No abstract available.</citation>
    <PMID>10233295</PMID>
  </results_reference>
  <results_reference>
    <citation>Cursi IB, Silva RT, Succi IB, Bernardes-Engemann AR, Orofino-Costa R. Onychomycosis due to Neoscytalidium treated with oral terbinafine, ciclopirox nail lacquer and nail abrasion: a pilot study of 25 patients. Mycopathologia. 2013 Feb;175(1-2):75-82. doi: 10.1007/s11046-012-9580-5. Epub 2012 Sep 14.</citation>
    <PMID>22976905</PMID>
  </results_reference>
  <results_reference>
    <citation>Tosti A, Piraccini BM, Lorenzi S. Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases. J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):217-24. doi: 10.1016/S0190-9622(00)90129-4.</citation>
    <PMID>10642676</PMID>
  </results_reference>
  <results_reference>
    <citation>Welsh O, Vera-Cabrera L, Welsh E. Onychomycosis. Clin Dermatol. 2010 Mar 4;28(2):151-9. doi: 10.1016/j.clindermatol.2009.12.006.</citation>
    <PMID>20347657</PMID>
  </results_reference>
  <results_reference>
    <citation>Gupta AK, Drummond-Main C, Cooper EA, Brintnell W, Piraccini BM, Tosti A. Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol. 2012 Mar;66(3):494-502. doi: 10.1016/j.jaad.2011.02.038. Epub 2011 Aug 4.</citation>
    <PMID>21820203</PMID>
  </results_reference>
  <results_reference>
    <citation>Bunyaratavej S, Prasertworonun N, Leeyaphan C, Chaiwanon O, Muanprasat C, Matthapan L. Distinct characteristics of Scytalidium dimidiatum and non-dermatophyte onychomycosis as compared with dermatophyte onychomycosis. J Dermatol. 2015 Mar;42(3):258-62. doi: 10.1111/1346-8138.12768. Epub 2015 Jan 13.</citation>
    <PMID>25639524</PMID>
  </results_reference>
  <results_reference>
    <citation>Bunyaratavej S, Leeyaphan C, Rujitharanawong C, Surawan TM, Muanprasat C, Matthapan L. Efficacy of 5% amorolfine nail lacquer in Neoscytalidium dimidiatum onychomycosis. J Dermatolog Treat. 2016 Aug;27(4):359-63. doi: 10.3109/09546634.2015.1109029. Epub 2015 Nov 11.</citation>
    <PMID>26471716</PMID>
  </results_reference>
  <results_reference>
    <citation>Gupta AK, Paquet M, Simpson FC. Therapies for the treatment of onychomycosis. Clin Dermatol. 2013 Sep-Oct;31(5):544-54. doi: 10.1016/j.clindermatol.2013.06.011.</citation>
    <PMID>24079583</PMID>
  </results_reference>
  <results_reference>
    <citation>Machouart M, Menir P, Helenon R, Quist D, Desbois N. Scytalidium and scytalidiosis: what's new in 2012? J Mycol Med. 2013 Mar;23(1):40-6. doi: 10.1016/j.mycmed.2013.01.002. Epub 2013 Feb 15.</citation>
    <PMID>23416171</PMID>
  </results_reference>
  <results_reference>
    <citation>James JE, Santhanam J, Lee MC, Wong CX, Sabaratnam P, Yusoff H, Tzar MN, Razak MF. In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia. Mycopathologia. 2017 Apr;182(3-4):305-313. doi: 10.1007/s11046-016-0085-5. Epub 2016 Nov 4.</citation>
    <PMID>27815659</PMID>
  </results_reference>
  <results_reference>
    <citation>Lurati M, Baudraz-Rosselet F, Vernez M, Spring P, Bontems O, Fratti M, Monod M. Efficacious treatment of non-dermatophyte mould onychomycosis with topical amphotericin B. Dermatology. 2011;223(4):289-92. doi: 10.1159/000335093. Epub 2012 Jan 10.</citation>
    <PMID>22236569</PMID>
  </results_reference>
  <results_reference>
    <citation>Hussain A, Samad A, Singh SK, Ahsan MN, Haque MW, Faruk A, Ahmed FJ. Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation. Drug Deliv. 2016;23(2):642-47. doi: 10.3109/10717544.2014.933284. Epub 2014 Jul 11.</citation>
    <PMID>25013957</PMID>
  </results_reference>
  <results_reference>
    <citation>Zaioncz S, Khalil NM, Mainardes RM. Exploring the Role of Nanoparticles in Amphotericin B Delivery. Curr Pharm Des. 2017;23(3):509-521. doi: 10.2174/1381612822666161027103640.</citation>
    <PMID>27799043</PMID>
  </results_reference>
  <results_reference>
    <citation>Ungpakorn R, Lohaprathan S, Reangchainam S. Prevalence of foot diseases in outpatients attending the Institute of Dermatology, Bangkok, Thailand. Clin Exp Dermatol. 2004 Jan;29(1):87-90. doi: 10.1111/j.1365-2230.2004.01446.x.</citation>
    <PMID>14723731</PMID>
  </results_reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>September 24, 2021</last_update_submitted>
  <last_update_submitted_qc>September 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fungal infection</keyword>
  <keyword>onychomycosis</keyword>
  <keyword>amphotericin B</keyword>
  <keyword>Dimethylsulphoxide</keyword>
  <keyword>non-dermatophyte</keyword>
  <keyword>randomized double blind controlled trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Onychomycosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amphotericin B</mesh_term>
    <mesh_term>Liposomal amphotericin B</mesh_term>
    <mesh_term>Dimethyl Sulfoxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03814343
org study id: 799/2018
nct id: NCT03814343
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The randomized control trial study aimed to evaluate effectiveness and safety of amphotericin
      B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment.
Introduction Onychomycosis caused by non-dermatophyte molds (NDMs) have become more common in
      clinical practice, particularly in tropical and subtropical area. With worldwide prevalence
      as high as 10-24% for nail infection, more recent studies have focused on the treatment
      regimens for NDMs onychomycosis, especially of Neoscytalidium spp and Fusarium spp. etiology.
      However, there has been no consensus to-date regarding standard treatment of choice for NDMs
      onychomycosis.

      NDMs onychomycosis was considered to be recalcitrant infection. Previous in vitro study in
      Malaysia reported high susceptibility of Neoscytalidium dimidiatum in amphotericin B,
      voriconazole, and miconazole treatment.Different therapeutic approaches such as oral
      antifungal agents, keratolytic agents, combined oral antifungal agents with keratolytic
      agents, or surgical nail avulsion, have been implemented but none has been considered a gold
      standard protocol in NDMs onychomycosis.

      Amphotericin B is the polyene class of antimicrobial compounds. Its properties are fungicidal
      and have a broad spectrum with a low rate of resistance. In in vitro study, amphotericin B
      was reported to have better efficacy of treating N. dimidiatum infection followed by
      terbinafine and voricanazole. The mechanism of action is the interaction with ergosterol of
      fungi membrane resulting in forming permeable channels in cellular membrane of targeted
      fungi. This causes impairing membrane barrier function. In addition, it also causes growth
      inhibition. Amphotericin B is often used in treating disseminated fungal infection and
      visceral leishmaniasis. However, Amphotericin B can cause several side effects including
      nephrotocixicity, fever, chills, nausea, vomiting, headache, anemia, electrolytes imbalance
      (hypokalemia and hypomagnesaemia). Oral amphotercin B has poor bioavailability. Topical forms
      are not commonly used due to its highly lipophilic property. As a consequence, topical
      amphotericin B is not well absorbed through mucosa or skin resulting in low efficacy. High
      dose of topical amphotericin B had been developed but the results didn't work well because it
      caused severe adverse events such as blistering, itching, redness, peeling or severe
      irritation of the skin and did not even achieve the goal of treatment.

      Dimethylsulphoxide (DMSO) is a promising vehicle to enhance the penetration of the drugs to
      animal or human skin. In addition, DMSO also has fungicidal activity. In vitro release study
      of amphotericin B from amphotericin B in 30% DMSO solution conducted in Siriraj Hospital
      revealed adequate amphotericin B concentration in the nails.

      Since skin and nail infections caused by NDMs especially N. dimidiatum has been diagnosed in
      many countries with the majority cases being reported from Thailand, it could be implied that
      N. dimidiatum was endemic pathogens in this area. Published data on treatment regimens of
      NDMs nail infection using amphotericin B are still limited. According to the high antifungal
      property and low rate of drug resistance of amphotericin B, this randomized control trial
      study aimed to evaluate effectiveness and safety of amphotericin B in 30% DMSO solution
      comparing with 30% DMSO solution.

      Objectives

        1. To evaluate effectiveness including mycological cure of amphotericin B in 30% DMSO
           solution comparing with 30% DMSO solution in NDMs onychomycosis treatment

        2. To evaluate safety of amphotericin B in 30% DMSO solution comparing with 30% DMSO
           solution in NDMs onychomycosis treatment

      Material and Methods Patients Since there was no previous study that compared amphotericin B
      in 30% DMSO with pure 30% DMSO in treating of NDMs onychomycosis, this study designated a
      total of 20 patients into two groups as 10 patients with NDMs onychomycosis treated with 30%
      DMSO (control group) and another 10 Patients with NDMs onychomycosis treated with
      amphotericin B in 30% DMSO. NDMs onychomycosis was diagnosed with diagnostic criteria for NDM
      onychomycosis proposed by Gupta et al. Patients with any systemic or topical antifungal
      agents at least 3 months prior to the study were excluded from this study.

      Design of medication Drugs were prepared in two solutions. First, amphotericin B (Alpharma,
      Denmark) was mixed with 30% DMSO (Sigma- Aldrich, Buchs, Switzerland) in 50:50 ratio. A final
      concentration of amphotericin B was 2 mg/ml. Later solution was pure 30% DMSO without
      amphotericin B. Those two final solutions had the same appearance, odor and texture. The
      solution will be kept in amber glass bottles with aluminum foil together with dropper. The
      drug regimen is to apply 1-3 drops of the solution once a day to each affected nail and
      briefly let the solution evaporate before continuing their usual activities.

      Treatment, Follow-up and measurement A randomized control trial study conducted in outpatient
      nail clinic, Siriraj Hospital. Patients will be divided into two groups by mixed block of
      randomization. First groups will be treated with amphotericin B in 30% DMSO solution. Another
      group will be given only 30% DMSO solution. Each patient is subjected to continuously apply
      his/ her own drugs followed instruction given for 12 weeks. They will be followed up at 12
      weeks, 24 weeks and 36 weeks for re-evaluation of clinical, mycological laboratories,
      adherence to the drug and adverse events. Effectiveness was evaluated by clinical improvement
      and mycological cure as well as median time to mycological cure. Clinical evaluation would be
      assessed by two treatment-blind dermatologists. Regarding mycological cure, it was defined as
      negative KOH and fungal culture. Data were analyzed using PASW Statistics version 18 (SPSS,
      Inc., Chicago, IL, USA).

      Duration of study: 1 year

      Study design: Randomized double blind control trial
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized double blind controlled trial pilot study
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double blind controlled trial between participants, drug preparing team, doctors, investigators, and outcome assessors.
measure: Effectiveness of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment
time frame: 36 weeks
description: Effectiveness was evaluated by patients who had negative on mycological laboratory (mycological cure) as percentage.
measure: Median time to mycological cure of patients with amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment
time frame: 36 weeks
description: Median time to mycological cure were defined as time (days, months or years) that had negative on mycological laboratory
measure: Clinical cure of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment
time frame: 36 weeks
description: Clinical cure was defined as the patients had complete clinical improvement or having <10% nail involvement.
measure: Median time to clinical cure of patients with amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment
time frame: 36 weeks
description: Median time to clinical cure were defined as time (days, months or years) that had clinical improvement of the affected nails.
measure: Evaluate side effects of amphotericin B in 30% DMSO solution comparing with 30% DMSO solution in NDMs onychomycosis treatment
time frame: 12 weeks
description: Side effects was assessed by the percentage of patients developed any side effect such as erythema, burning sensation, pain.
arm group label: Active comparator
arm group type: Active Comparator
description: 10 patients with NDMs onychomycosis treated with amphotericin B in 30% DMSO.
arm group label: control comparator
arm group type: Placebo Comparator
description: 10 patients with NDMs onychomycosis treated with 30% DMSO.
intervention type: Drug
intervention name: amphotericin B in 30% DMSO
description: amphotericin B in 30% DMSO was given to patients in active comparators group for continuous 12 weeks.
arm group label: Active comparator
intervention type: Drug
intervention name: 30% DMSO
description: 30% DMSO was given to patients in placebo comparators group for continuous 12 weeks.
arm group label: control comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sumanas Bunyaratavej, MD
role: Principal Investigator
affiliation: Mahidol University
last name: Charussri Leeyaphan, MD
role: Study Director
affiliation: Mahidol University
facility: 
country: Thailand
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PMID: 24521698
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PMID: 21820203
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PMID: 25639524
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PMID: 26471716
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PMID: 24079583
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PMID: 14723731
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Onychomycosis
mesh term: Amphotericin B
mesh term: Liposomal amphotericin B
mesh term: Dimethyl Sulfoxide
sharing ipd: Undecided