HIV-1 InfectionPhase 3NCT01427738
Gentian Violet Vs. Nystatin Oral Suspension for Treatment of Oropharyngeal Candidiasis
A Phase 3 study testing Gentian Violet and Nystatin oral suspension in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 10 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Gentian Violet and Nystatin oral suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 10 sitesin 7 countries
- Study dates
- Jun 2011to Jan 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
Botswana2 sites
Gaborone Prevention/Treatment Trials CRS (12701)
Gaborone
Molepolole Prevention/Treatment Trials CRS (12702)
Molepolole
India2 sites
BJ Medical College CRS (31441)
Pune, Maharashtra, 411001
National AIDS Research Institute Pune CRS (11601)
Pune, Maharashtra, 411026
Kenya2 sites
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
Eldoret, 30100
Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
Kericho, 20200
About this study
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
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.
Read the 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.
- Conditions
- HIV-1 Infection
- Being tested
- Gentian Violet, Nystatin oral suspension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gentian VioletDrug
Participants were administered topical Gentian violet solution, orally, twice daily for 14 days.
Nystatin oral suspensionDrug
Participants were administered Nystatin oral suspension 4 times a day for 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Topical GV solution | Experimental | Topical GV 0.00165% solution (5 mL swish and gargle for 1 minute and expectorate [spit] 2 times per day [BID]) for 14 days Receives: Drug: Gentian Violet |
| Arm B: Nystatin oral suspension | Active comparator | Nystatin oral suspension (5 mL of 100,000 units/mL swish for 1 minute and swallow 4 times per day [QID]) for 14 days Receives: Drug: Nystatin oral suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 14 days of treatment
Secondary outcomes (6)
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.
Measured: after 14 days of treatment
Quantitative Yeast Colony Counts
If quantitative yeast culture yielding < 20 CFU/mL of Candida spp., then we call this mycological success
Measured: At weeks 0, 2, 6
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.)
Measured: After 14 days of treatment
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.
Measured: After 14 days of treatment
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)
Measured: Weeks 0, 6
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.
Measured: After 14 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2011 (estimated)
- Study startJun 2011
- Primary completionSep 2012
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Robert A Salata, MD, Study chair, Case CRSJames G Hakim, MD, Principal investigator, UZ- Parirenyatwa CRSTim Hodgson, MD, Principal investigator, Eastman Dental HospitalRichard J Jurevic, DDS, PhD, Principal investigator, Case CRSPranab K Mukherjee, PhD, MSc, Principal investigator, Case CRSCissy M Kityo, MBChB, MSc, Principal investigator, JCRC CRSRana Traboulsi, MD, Principal investigator, Case CRSSrikanth P Tripathy, MD, MBBS, Principal investigator, NARI Pune CRS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01427738
- Sponsor's protocol ID
- ACTG A5265
- Other IDs
- 1U01AI068636
- Status last verified
- Feb 2015
- First submitted
- 3 Nov 2010
- Last updated
- 16 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27677161
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01427738
- Acronym / sponsor ID
- ACTG A5265
- Conditions
- HIV-1 Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Jun 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 2 Sep 2011 (estimated)
- Results
- Posted 16 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Topical GV solution | Experimental | Drug: Gentian VioletTopical GV 0.00165% solution (5 mL swish and gargle for 1 minute and expectorate [spit] 2 times per day [BID]) for 14 days |
| Arm B: Nystatin oral suspension | Active comparator | Drug: Nystatin oral suspensionNystatin oral suspension (5 mL of 100,000 units/mL swish for 1 minute and swallow 4 times per day [QID]) for 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gentian VioletParticipants were administered topical Gentian violet solution, orally, twice daily for 14 days. | Drug | Arm A: Topical GV solution |
| Nystatin oral suspensionParticipants were administered Nystatin oral suspension 4 times a day for 14 days. | Drug | Arm B: Nystatin oral suspension |
Primary outcome
Number of Participants With Clinical Efficacy
Time frame: After 14 days of treatment
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.
6 secondary outcomes
Number of Participant With Symptom
Time frame: after 14 days of treatment
Quantitative Yeast Colony Counts
Time frame: At weeks 0, 2, 6
Tolerance
Time frame: After 14 days of treatment
Number of Participants Who Were Adherent.
Time frame: After 14 days of treatment
Self-Assessment of General Health
Time frame: Weeks 0, 6
Number of Participants Who Found GV and Nystatin Acceptable.
Time frame: After 14 days of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27677161Mukherjee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert A Salata, MD study chair
Case CRS
James G Hakim, MD principal investigator
UZ- Parirenyatwa CRS
Tim Hodgson, MD principal investigator
Eastman Dental Hospital
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gentian Violet and Nystatin oral suspension in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Botswana, India, Kenya, Malawi, South Africa and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinical Efficacy (time frame: After 14 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01427738, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2015.