Back to results

Gentian Violet Vs. Nystatin Oral Suspension for Treatment of Oropharyngeal Candidiasis

Primary Purpose

HIV-1 Infection

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Gentian Violet

Nystatin oral suspension

About this trial

This is an interventional treatment trial for HIV-1 Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Gaborone Prevention/Treatment Trials CRS (12701)
Molepolole Prevention/Treatment Trials CRS (12702)
BJ Medical College CRS (31441)
National AIDS Research Institute Pune CRS (11601)
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
College of Med. JHU CRS (30301)
Durban Adult HIV CRS (11201)
Joint Clinical Research Centre (JCRC) (12401)
UZ-Parirenyatwa CRS (30313)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A: Topical GV solution

Arm B: Nystatin oral suspension

Arm Description

Topical GV 0.00165% solution (5 mL swish and gargle for 1 minute and expectorate [spit] 2 times per day [BID]) for 14 days

Nystatin oral suspension (5 mL of 100,000 units/mL swish for 1 minute and swallow 4 times per day [QID]) for 14 days

Outcomes

Primary Outcome Measures

Number of Participants With Clinical Efficacy

The primary endpoint is clinical efficacy defined as cure (absence of lesions) or improvement (a decrease in severity of lesions) after 14 days of treatment. The oral cavity will be split arbitrarily into 6 sites: left lower and upper labial mucosa and buccal mucosa, right lower and upper labial mucosa and buccal mucosa, hard palate, soft palate, tongue (dorsum, lateral, and ventral), and floor of mouth. Severity is scored using a scoring system from 0 to 3 (0 corresponds to absence of lesions, and 3 corresponds to presence of extensive confluent lesions) which leads to a composite severity score ranging from 0 to 18 after adding up the scores from all 6 sites. Complete success is assigned if the composite score after treatment equals to 0. Improved/partial response is assigned if the composite score after treatment is less than the baseline score. The blinded evaluator scores the severity of lesions by examining different lesion characteristics.

Secondary Outcome Measures

Number of Participant With Symptom

Symptoms were assessed using a visual analog scale where the level of discomfort and pain were recorded and quantified using a scoring system from 0 to 3. 0=no discomfort/pain; 1=mild discomfort/pain; 2=Moderate discomfort/pain; 3=Severe discomfort/pain.

Quantitative Yeast Colony Counts

If quantitative yeast culture yielding < 20 CFU/mL of Candida spp., then we call this mycological success

Tolerance

The investigators will measure tolerance using a scale from 0 to 3 (0=No side effects experienced, no changes in treatment; 1=Some side effects experienced, but not enough to modify treatment; 2=Some side effects experienced, resulted in treatment interruption; 3=Side effects experienced, resulted in treatment discontinuation.)

Number of Participants Who Were Adherent.

Adherence was reported as a dichotomous variable (adherence vs. non-adherence). Participants who have missing doses less than 15% will be considered as adherent, i.e., if a participant is in the GV arm, then the cutoff point is 28*0.15=4 doses; and for the nystatin arm is 56*0.15=8 doses.

Self-Assessment of General Health

Participants rated their general health on two scales. One is a five point scale ranging from 1 to 5 (1=Excellent; 2=Very Good; 3=Good; 4=Fair; 5=Poor)

Number of Participants Who Found GV and Nystatin Acceptable.

Acceptability was defined as the willingness to use the drug if it is proven effective to treat oral candidiasis. Participants were asked whether or not they would be willing to use the assigned treatment via questionnaires.

Full Information

NCT ID

NCT01427738

First Posted

November 3, 2010

Last Updated

February 12, 2015

Sponsor

AIDS Clinical Trials Group

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT01427738

Brief Title

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

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

June 2011 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AIDS Clinical Trials Group

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1 Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

221 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Topical GV solution

Arm Type

Experimental

Arm Description

Topical GV 0.00165% solution (5 mL swish and gargle for 1 minute and expectorate [spit] 2 times per day [BID]) for 14 days

Arm Title

Arm B: Nystatin oral suspension

Arm Type

Active Comparator

Arm Description

Nystatin oral suspension (5 mL of 100,000 units/mL swish for 1 minute and swallow 4 times per day [QID]) for 14 days

Intervention Type

Drug

Intervention Name(s)

Gentian Violet

Intervention Description

Participants were administered topical Gentian violet solution, orally, twice daily for 14 days.

Intervention Type

Drug

Intervention Name(s)

Nystatin oral suspension

Intervention Description

Participants were administered Nystatin oral suspension 4 times a day for 14 days.

Primary Outcome Measure Information:

Title

Number of Participants With Clinical Efficacy

Description

Time Frame

After 14 days of treatment

Secondary Outcome Measure Information:

Title

Number of Participant With Symptom

Description

Time Frame

after 14 days of treatment

Title

Quantitative Yeast Colony Counts

Description

If quantitative yeast culture yielding < 20 CFU/mL of Candida spp., then we call this mycological success

Time Frame

At weeks 0, 2, 6

Title

Tolerance

Description

Time Frame

After 14 days of treatment

Title

Number of Participants Who Were Adherent.

Description

Time Frame

After 14 days of treatment

Title

Self-Assessment of General Health

Description

Participants rated their general health on two scales. One is a five point scale ranging from 1 to 5 (1=Excellent; 2=Very Good; 3=Good; 4=Fair; 5=Poor)

Time Frame

Weeks 0, 6

Title

Number of Participants Who Found GV and Nystatin Acceptable.

Description

Time Frame

After 14 days of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials: