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

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ClinicalTrials.gov Identifier: NCT01427738
Recruitment Status : Completed
First Posted : September 2, 2011
Results First Posted : February 16, 2015
Last Update Posted : February 16, 2015
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Interventions Drug: Gentian Violet
Drug: Nystatin oral suspension
Enrollment 221

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Period Title: Overall Study
Started 110 111
Completed 91 90
Not Completed 19 21
Reason Not Completed
Death             12             9
Severe debilitation, unable to continue             0             1
Subject unable to get to clinic             5             2
Withdrawal by Subject             0             2
Subject not willing to adhere to reqs             1             2
Lost to Follow-up             1             5
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension Total
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Total of all reporting groups
Overall Number of Baseline Participants 110 111 221
Hide Baseline Analysis Population Description
All participants who enrolled.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 110 participants 111 participants 221 participants
10-19 years 0 1 1
20-29 years 17 30 47
30-39 years 54 52 106
40-49 years 21 17 38
50-59 years 16 9 25
Over 60 years 2 2 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 110 participants 111 participants 221 participants
Female
62
  56.4%
66
  59.5%
128
  57.9%
Male
48
  43.6%
45
  40.5%
93
  42.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 110 participants 111 participants 221 participants
Black Non-Hispanic 97 106 203
Asian, Pacific Islander 13 5 18
Antiretroviral Therapy Usage  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 110 participants 111 participants 221 participants
On ART 27 28 55
Not on ART 83 83 166
CD4 Count  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 110 participants 111 participants 221 participants
0-200 cells/microliter 87 88 175
> 200 cells/microliter 23 23 46
HIV RNA Viral Load  
Mean (Standard Deviation)
Unit of measure:  Log10(copies/ml)
Number Analyzed 110 participants 111 participants 221 participants
4.89  (1.31) 5.03  (1.21) 4.96  (1.26)
1.Primary Outcome
Title Number of Participants With Clinical Efficacy
Hide Description 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.
Time Frame After 14 days of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Out of 221 subjects,17 had oral exams at entry but not week 2: 11 premature discontinuation, 2 missed visits, and 4 without specific reasons. 204 subjects received oral exams at both entry and week 2. 2 more participants were excluded from the final analysis because they had no pseudomem candi at entry, which led to a total of 202 subjects.
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 100 102
Measure Type: Number
Unit of Measure: participants
76 73
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Topical GV Solution, Arm B: Nystatin Oral Suspension
Comments Repeated confidence intervals (RCIs) were used to control type I error.A interim analysis was conducted by a 99.7% CI. The final analyses use a 95.1% CI, based on the Lan-DeMets error-spending function corresponding to the O’Brien-Fleming boundary.76% of 100 participant in arm GV had cure or improvement of OC after 14 days of treatment, and 71.6% of 102 in arm nystatin had cure or improvement of OC. Difference in clinical efficacy rates between GV and nystatin 95.1% CI is 0.044 (-0.077, 0.166).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportion with clinical e
Estimated Value 0.044
Confidence Interval (2-Sided) 95.1%
-0.077 to 0.166
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participant With Symptom
Hide Description 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.
Time Frame after 14 days of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
At entry, a total of 217 observations (106 in GV arm; 111 in nystatin arm) were available to evaluate the symptoms (pain and discomfort) associated with OC. At the end of treatment, a total of 204 observations were available to evaluate the symptoms associated with OC using extended Mantel-Haenszel test between GV and nystatin arms.
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 106 111
Measure Type: Number
Unit of Measure: participants
Pain at entry 106 111
Pain at end of treatment 102 102
Discomfort at entry 106 111
Discomfort at end of treatment 102 102
3.Secondary Outcome
Title Quantitative Yeast Colony Counts
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

At entry, 210 observations were available (182 had positive culture result for Candida specimen, and 175 of those had colony count performed) to evaluate quantitative yeast colony counts.

N= 78 (GV), 70 (Nystatin) at end of treatment; N= 51 (GV), 35 (Nystatin) at week 6;

Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 88 87
Mean (Standard Deviation)
Unit of Measure: CFU/mL
At entry, week 0 7.2497  (2.2382) 7.0037  (2.0584)
At end of treatment (week 2) 6.9374  (2.1438) 5.8888  (2.3970)
At week 6 6.7388  (2.3469) 6.5929  (2.3668)
4.Secondary Outcome
Title Tolerance
Hide Description 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.)
Time Frame After 14 days of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis for tolerance was based on 208 observations.
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 103 105
Measure Type: Number
Unit of Measure: participants
No side effects, no changes in treatment 100 98
Some side effects, no changes in treatment 3 6
Some side effects, treatment interruption 0 1
5.Secondary Outcome
Title Number of Participants Who Were Adherent.
Hide Description 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.
Time Frame After 14 days of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis for adherence was based on 209 observations.
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 104 105
Measure Type: Number
Unit of Measure: participants
Adherent 95 95
Non-adherent 9 10
6.Secondary Outcome
Title Self-Assessment of General Health
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
N=110 (GV), 110 (Nystatin) wk 0 N= 96 (GV), 95 (Nystatin) wk 6
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 110 110
Measure Type: Number
Unit of Measure: participants
Week 0: Excellent 1 4
Week 0: Very Good 13 11
Week 0: Good 52 56
Week 0: Fair 39 30
Week 0: Poor 5 9
Week 6: Excellent 5 7
Week 6: Very Good 29 25
Week 6: Good 42 42
Week 6: Fair 18 18
Week 6: Poor 2 3
7.Secondary Outcome
Title Number of Participants Who Found GV and Nystatin Acceptable.
Hide Description 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.
Time Frame After 14 days of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis for acceptability of treatment was based on 209 subjects.
Arm/Group Title Arm A: Topical GV Solution Arm B: Nystatin Oral Suspension
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

Overall Number of Participants Analyzed 104 105
Measure Type: Number
Unit of Measure: participants
100 98
Time Frame From entry (week 0) to end of study.
Adverse Event Reporting Description The protocol requested reporting of grade 3 or higher of adverse events and any adverse event that led to a change in study treatment, regardless of grade. Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009), was used for grading
 
Arm/Group Title Gentian Violet Nystatin
Hide Arm/Group 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

Gentian Violet: Participants will be administered topical Gentian violet solution, orally, twice daily 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

Nystatin oral suspension: Participants will be administered Nystatin oral suspension 4 times a day for 14 days.

All-Cause Mortality
Gentian Violet Nystatin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Gentian Violet Nystatin
Affected / at Risk (%) Affected / at Risk (%)
Total   18/110 (16.36%)   17/111 (15.32%) 
Blood and lymphatic system disorders     
Anaemia  1  2/110 (1.82%)  2/111 (1.80%) 
Neutropenia  1  0/110 (0.00%)  1/111 (0.90%) 
Cardiac disorders     
Cardiac failure congestive  1  0/110 (0.00%)  1/111 (0.90%) 
General disorders     
Death  1  2/110 (1.82%)  1/111 (0.90%) 
Hepatobiliary disorders     
Hepatotoxicity  1  0/110 (0.00%)  1/111 (0.90%) 
Infections and infestations     
Encephalitis viral  1  1/110 (0.91%)  0/111 (0.00%) 
Gastroenteritis  1  2/110 (1.82%)  1/111 (0.90%) 
HIV infection WHO clinical stage IV  1  1/110 (0.91%)  0/111 (0.00%) 
Malaria  1  0/110 (0.00%)  1/111 (0.90%) 
Meningitis  1  0/110 (0.00%)  1/111 (0.90%) 
Meningitis bacterial  1  0/110 (0.00%)  2/111 (1.80%) 
Meningitis cryptococcal  1  1/110 (0.91%)  0/111 (0.00%) 
Oesophageal candidiasis  1  1/110 (0.91%)  0/111 (0.00%) 
Pneumocystis jirovecii pneumonia  1  0/110 (0.00%)  1/111 (0.90%) 
Pneumonia  1  2/110 (1.82%)  0/111 (0.00%) 
Pulmonary tuberculosis  1  3/110 (2.73%)  2/111 (1.80%) 
Sepsis  1  0/110 (0.00%)  1/111 (0.90%) 
Septic shock  1  0/110 (0.00%)  1/111 (0.90%) 
Investigations     
Hepatic enzyme increased  1  0/110 (0.00%)  1/111 (0.90%) 
Liver function test abnormal  1  0/110 (0.00%)  1/111 (0.90%) 
Neutrophil count decreased  1  0/110 (0.00%)  1/111 (0.90%) 
Nervous system disorders     
Cerebrovascular accident  1  1/110 (0.91%)  0/111 (0.00%) 
Renal and urinary disorders     
Nephropathy  1  0/110 (0.00%)  1/111 (0.90%) 
Renal failure acute  1  1/110 (0.91%)  0/111 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  1  1/110 (0.91%)  0/111 (0.00%) 
Pulmonary embolism  1  0/110 (0.00%)  1/111 (0.90%) 
Vascular disorders     
Hypotension  1  0/110 (0.00%)  1/111 (0.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gentian Violet Nystatin
Affected / at Risk (%) Affected / at Risk (%)
Total   103/110 (93.64%)   101/111 (90.99%) 
Gastrointestinal disorders     
Cheilitis  1  9/110 (8.18%)  5/111 (4.50%) 
Diarrhoea  1  6/110 (5.45%)  6/111 (5.41%) 
Leukoplakia oral  1  6/110 (5.45%)  4/111 (3.60%) 
Odynophagia  1  6/110 (5.45%)  3/111 (2.70%) 
Oral disorder  1  11/110 (10.00%)  14/111 (12.61%) 
Oral mucosal erythema  1  5/110 (4.55%)  8/111 (7.21%) 
Stomatitis  1  7/110 (6.36%)  6/111 (5.41%) 
General disorders     
Chest pain  1  8/110 (7.27%)  10/111 (9.01%) 
Pyrexia  1  5/110 (4.55%)  9/111 (8.11%) 
Infections and infestations     
Oral candidiasis  1  31/110 (28.18%)  26/111 (23.42%) 
Oral hairy leukoplakia  1  6/110 (5.45%)  11/111 (9.91%) 
Pneumonia bacterial  1  5/110 (4.55%)  8/111 (7.21%) 
Pulmonary tuberculosis  1  9/110 (8.18%)  6/111 (5.41%) 
Investigations     
Alanine aminotransferase increased  1  12/110 (10.91%)  6/111 (5.41%) 
Aspartate aminotransferase increased  1  31/110 (28.18%)  26/111 (23.42%) 
Blood albumin decreased  1  58/110 (52.73%)  53/111 (47.75%) 
Blood alkaline phosphatase increased  1  18/110 (16.36%)  11/111 (9.91%) 
Blood bicarbonate decreased  1  21/110 (19.09%)  20/111 (18.02%) 
Blood calcium decreased  1  43/110 (39.09%)  50/111 (45.05%) 
Blood creatinine increased  1  7/110 (6.36%)  5/111 (4.50%) 
Blood glucose decreased  1  1/110 (0.91%)  6/111 (5.41%) 
Blood glucose increased  1  7/110 (6.36%)  9/111 (8.11%) 
Blood magnesium decreased  1  11/110 (10.00%)  10/111 (9.01%) 
Blood phosphorus decreased  1  10/110 (9.09%)  10/111 (9.01%) 
Blood potassium decreased  1  9/110 (8.18%)  11/111 (9.91%) 
Blood sodium decreased  1  52/110 (47.27%)  37/111 (33.33%) 
Blood uric acid increased  1  10/110 (9.09%)  20/111 (18.02%) 
Haemoglobin decreased  1  33/110 (30.00%)  33/111 (29.73%) 
Neutrophil count decreased  1  22/110 (20.00%)  29/111 (26.13%) 
White blood cell count decreased  1  17/110 (15.45%)  23/111 (20.72%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  9/110 (8.18%)  9/111 (8.11%) 
Oropharyngeal plaque  1  7/110 (6.36%)  0/111 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01427738     History of Changes
Obsolete Identifiers: NCT01494129
Other Study ID Numbers: ACTG A5265
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: November 3, 2010
First Posted: September 2, 2011
Results First Submitted: January 6, 2015
Results First Posted: February 16, 2015
Last Update Posted: February 16, 2015