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A Trial of the Efficacy and Safety of Topical Nitric Oxide in Patients With Anogenital Warts

Phase 2
Completed
Conditions
Condylomata Acuminata
Anogenital Warts
Interventions
Drug: Placebo
Registration Number
NCT02015260
Lead Sponsor
University of Aberdeen
Brief Summary

Objective To assess the efficacy of the topical application of Nitric Oxide, delivered using acidified nitrite.

Design Multicentre, randomized, controlled, dose ranging trial. A control arm and three doses of acidified nitrite applied topically for 12 weeks with a further 12 weeks of follow up.

Setting The trial setting was in European genitourinary medicine clinics

Participants Male and female volunteers over 18 years of age with between 2 and 50 ano-genital warts, 328 were screened for eligibility and 299 subjects from 40 centres were randomised.

Exclusions Pregnancy; concomitant Sexually Transmitted Disease; internal warts requiring treatment other than surgery /laser; diabetes ; Human Immunodeficiency Virus-positive, immunosuppressed and/or using immunosuppressive therapies; drug abuse.

interventions compared

* Control Placebo nitrite cream and placebo citric acid cream twice daily

* A) 3% sodium nitrite + 4.5% citric acid creams twice daily

* B) 6% sodium nitrite + 9% citric acid creams once daily

* C) 6% sodium nitrite + 9% citric acid creams twice daily

Outcomes

* Primary proportion of patients with complete clearance of target warts Secondary

* Time to clearance

* Wart area

* Wart count

* Patient and investigator assessment of efficacy

* Safety

* Tolerability

* Adherence

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
299
Inclusion Criteria
  • Males and females over 18 years of age
  • 2-50 warts in the anogenital region.
  • Female patients of child-bearing potential had to be willing to use a non-barrier method of contraception at entry and for the duration of the study.
  • all patients had to be willing to use barrier protection for the duration of the study.
  • All patients had to be able to comply with the requirements of the protocol and be likely to return for follow-up visits and had to be contactable for the duration of the study.
Exclusion Criteria
  • Patients with clinically relevant abnormal haematology or biochemistry results (determined from the sample taken at Visit 1).
  • Patients who had used an active therapy for anogenital warts within 2 weeks of randomisation to study drug, i.e. Visit 2.
  • Patients who had used any local supportive medication, including topical corticosteroids or beta-interferon, within 2 weeks of study entry.
  • Patients who had used medication known to adversely affect their haematology profile, including local anaesthetics (benzocaine, lidocaine, etc), nitrofurantoin, sulphonylureas and sulphonamides within 2 weeks of study entry. [Word 'adversely' added by Protocol Amendment 2, 7 May 2002.]
  • Patients with abnormal anogenital skin, such as eczema, or skin that had not healed following surgery (cryosurgery, laser ablation or similar).
  • Patients who were known to have a concomitant sexually transmitted disease that inhibited accurate assessment of their warts.
  • Patients who required treatment other than surgery or laser for internal warts.
  • Male patients with intra-urethral warts [deleted by Protocol Amendment 2, 7 May 2002].
  • Patients with diabetes (Type I or Type II diabetes).
  • Patients who were known to be HIV-positive.
  • Patients who were known to be immunosuppressed and/or using immunosuppressive therapies.
  • Patients known to abuse alcohol and/or drugs or with a history of chronic alcohol or drug abuse.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboPlaceboplacebo 0% nitrite cream and placebo 0% citric acid cream
Topical NO Dose ATopical NO3% sodium nitrite + 4.5% citric acid twice daily
Topical NO Dose BTopical NO6% sodium nitrite + 9% citric acid once daily
Topical NO Dose CTopical NO6% sodium nitrite + 9% citric acid twice daily
Primary Outcome Measures
NameTimeMethod
Proportion of patients with complete clearance of target warts in Intention to treat (ITT) population24 weeks

* Number of and area of target warts (up to 10 selected) at Baseline and Week 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at follow-up (Weeks 4, 8 and 12 after end of treatment)

* Number of warts at Baseline (Week 0) and of remaining baseline warts at Week 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at Weeks 4, 8 and 12 of follow-up

Secondary Outcome Measures
NameTimeMethod
Investigator assessment of efficacy12 weeks

Investigator assessment of efficacy (categorised as complete clearance, significant improvement, partial improvement, no change or worsening) at Week 12/withdrawal/early completion

Patient assessment of tolerability12

Patient assessment of itching, pain and burning (categorised as none, mild, moderate or severe) at treatment site at Screening and Weeks 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion

Safety of treatment12 weeks and followed up

Adverse events throughout treatment period; unresolved events at end of treatment were followed up Heart rate and blood pressure at each visit during treatment Laboratory tests at Screening and Week 12/withdrawal/early completion Physical examination at Screening and at Week 12/withdrawal/early completion.

Total number of warts (baseline and new) at end of treatment12 weeks
Patient assessment of efficacy12 weeks

Patient assessment of efficacy (categorised as complete clearance, significant improvement, partial improvement, no change or worsening) at Week 12/withdrawal/early completion

Investigator assessment of tolerability12 weeks

Investigator assessment of erythema/eschar and oedema (using modified Draize scales from 0 to 4) at Baseline (Week 0), Weeks 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at follow-up (Weeks 4, 8 and 12 after end of treatment)

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