Clinical trial NCT01427738: Gentian Violet Vs. Nystatin Oral Suspension for Treatment of Oropharyngeal Candidiasis
Official title: A Phase III, Open-Label, Randomized, Assessment-Blinded Clinical Trial to Compare the Safety and Efficacy of Gentian Violet Oral Solution to That of Nystatin Oral Suspension for the Treatment of Oropharyngeal Candidiasis in HIV-1 Infected Participants in Non-U.S. Settings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2011-09-02
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to see which one of two medicines (topical gentian violet \[GV\] or nystatin oral suspension) was better than the other in treating Oral Candidiasis (OC). This was measured by whether the study participant still had OC or sores in his/her mouth after 14 days of treatment. Also, safety and tolerability of GV and nystatin in the treatment of OC were assessed.

Detailed description: A5265 was a phase III, open-label (both the researchers and participants know which treatment was being administered) clinical trial to compare the safety and efficacy of topical GV to that of oral nystatin suspension. Male and female HIV-1 positive participants ≥ 18 years of age were randomized (as if by the toss of a coin) with equal probability and stratified by CD4+ T-cell counts and the use of antiretroviral therapy at the time of study entry to receive either topical GV solution (5 mL swish and gargle for 1 minute and spit two times daily) or nystatin oral suspension (5 mL swish for 1 minute and swallow four times daily) for 14 days. Therapy was considered as failed if participants have no clinical improvement (assessed by severity of pseudomembranous candidiasis) during either treatment regimen. Evaluation of signs and symptoms of oral candidiasis was done by an evaluator who was blinded to the treatment assignment. A total of 494 participants was expected to enroll in the study but due to early study closure only 221 enrolled; and participants are expected to be on the study for about 13 weeks.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
* Pseudomembranous candidiasis documented by a complete oral exam (i.e., white or yellow spots or plaques with an underlying erythematous base, located in any part of the oral cavity) at the screening visit. Participants with documented angular chelitis and/or erythematous candidiasis without pseudomembranous candidiasis were not eligible to enroll in the study.
* If on an antiretroviral therapy (ART), initiation of regimen at least 12 weeks prior to study entry, and willingness of participant to remain on current ART regimen until the study-defined 14-day treatment period was complete. NOTE: Participants who were not ART-naïve and not on ART were eligible to participate in the study if they did not intend to initiate ART during the study- defined 14-day treatment period.
* CD4+ cell count obtained within 30 days prior to study entry at a DAIDS-approved laboratory.

Exclusion Criteria:

* Documented or presumptive signs or symptoms of esophageal candidiasis (e.g., dysphagia) during the screening period unless endoscopic examination of the esophagus was performed, and fungal esophagitis were excluded.
* Use of any investigational drug currently or within 30 days prior to study entry. NOTE: For purposes of this study, drugs available under an FDA-authorized expanded access program was NOT considered investigational.
* Concurrent vaginal candidiasis within 21 days prior to study entry.
* Use of inhaled or systemic corticosteroids within 14 days prior to study entry.
* Use of any antifungal agents within 30 days prior to study entry.
* Anticipated need for systemic or oral/topical antifungal agents for other diagnoses within the study-defined 14-day treatment period.
* Intend to initiate ART during the screening period, at study entry, or within the study-defined 14-day treatment period.
* Intend to use any additional oral topical treatments within the study- defined 14-day treatment period.
* Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
* Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Serious illness, in the opinion of the site investigator, requiring systemic treatment.
* Hospitalization within 30 days prior to study entry for HIV or HIV-related conditions.
* Previous or current history of porphyria.
* Presence of oral warts during the screening period or at the study entry visit before randomization.
* Current wearing of full dentures or a maxillary partial denture at study entry

Primary outcomes:
measure: Number of Participants With Clinical Efficacy
timeFrame: After 14 days of treatment
Secondary outcomes:
measure: Number of Participant With Symptom
timeFrame: after 14 days of treatment
measure: Quantitative Yeast Colony Counts
timeFrame: At weeks 0, 2, 6
measure: Tolerance
timeFrame: After 14 days of treatment
measure: Number of Participants Who Were Adherent.
timeFrame: After 14 days of treatment
measure: Self-Assessment of General Health
timeFrame: Weeks 0, 6
measure: Number of Participants Who Found GV and Nystatin Acceptable.
timeFrame: After 14 days of treatment
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Gaborone Prevention/Treatment Trials CRS (12701)
city: Molepolole
country: Botswana
facility: Molepolole Prevention/Treatment Trials CRS (12702)
city: Pune
country: India
facility: BJ Medical College CRS (31441)
state: Maharashtra
city: Pune
country: India
facility: National AIDS Research Institute Pune CRS (11601)
state: Maharashtra
city: Eldoret
country: Kenya
facility: AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
city: Kericho
country: Kenya
facility: Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
city: Blantyre
country: Malawi
facility: College of Med. JHU CRS (30301)
city: Durban
country: South Africa
facility: Durban Adult HIV CRS (11201)
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre (JCRC) (12401)
city: Harare
country: Zimbabwe
facility: UZ-Parirenyatwa CRS (30313)
Study officials:
affiliation: Case CRS
name: Robert A Salata, MD
role: STUDY_CHAIR
affiliation: UZ- Parirenyatwa CRS
name: James G Hakim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eastman Dental Hospital
name: Tim Hodgson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case CRS
name: Richard J Jurevic, DDS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case CRS
name: Pranab K Mukherjee, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: JCRC CRS
name: Cissy M Kityo, MBChB, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Case CRS
name: Rana Traboulsi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NARI Pune CRS
name: Srikanth P Tripathy, MD, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Mahmoud A Ghannoum, Phd, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mukherjee PK, Chen H, Patton LL, Evans S, Lee A, Kumwenda J, Hakim J, Masheto G, Sawe F, Pho MT, Freedberg KA, Shiboski CH, Ghannoum MA, Salata RA; Oral HIVAIDS Research Alliance (OHARA)AIDS Clinical Trials Group (ACTG) 5265 Team. Topical gentian violet compared with nystatin oral suspension for the treatment of oropharyngeal candidiasis in HIV-1-infected participants. AIDS. 2017 Jan 2;31(1):81-88. doi: 10.1097/QAD.0000000000001286.