Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.
OBJECTIVE
Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs.


OBJECTIVE
To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite.


METHODS
A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003.


METHODS
Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily).


METHODS
The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety.


RESULTS
Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose-related increase in itching, pain, edema, and staining of the anogenital skin associated with the active treatment. Overall, 21 patients withdrew from active treatment because of adverse events compared with none using placebo.


CONCLUSIONS
Use of sodium nitrite, 6%, with citric acid, 9%, twice daily is more effective than placebo in the treatment of anogenital warts. Treatment was associated with local irritant adverse effects.


BACKGROUND
clinicaltrials.gov Identifier: NCT02015260.
Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, Scotland.
Anthony D
AD
Ormerod
Department of Dermatology, University Medical Centre, Groningen, Groningen, the Netherlands.
Pieter C
PC
van Voorst Vader
Department of Dermatology and Venereology, Medical University of Warsaw, Warsaw, Poland.
Slovomir
S
Majewski
Paula-Modersohn-Platz Freiburg, Germany.
Wolfgang
W
Vanscheidt
University of Exeter Medical School, University of Exeter, St Luke's Campus, Exeter, England.
Nigel
N
Benjamin
Department of Dermatology, Erasmus Medical Centre, Rotterdam, the Netherlands7Department of Dermatology, Havenziekenhuis, Rotterdam, the Netherlands.
Willem
W
van der Meijden
D000287:Administration, Topical; D000328:Adult; D001004:Anus Diseases / Q000188:drug therapy* / Q000821:virology; D019343:Citric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003218:Condylomata Acuminata / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D019343:Citric Acid; D012977:Sodium Nitrite