Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Use of Cidofovir for Recurrent Respiratory Papillomatosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00205374
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : July 18, 2017
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 20, 2005
Results First Submitted Date  ICMJE February 22, 2013
Results First Posted Date  ICMJE July 18, 2017
Last Update Posted Date February 26, 2019
Study Start Date  ICMJE November 1999
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
Change in Papilloma Severity [ Time Frame: Baseline, 2 months, and 12 months ]
Derkay Severity Score. Minimum Score is Zero. Maximum score is 86. Treatment of RRP with cidofovir injection will be considered efficacious if drug group patients experience clinically or statistically significant changes in papilloma severity and inter-surgery time intervals (relative to pre-treatment assessments), when compared with placebo group patients. The scale rates - Voice (normal 0, abnormal 1, aphonic 2) Stridor (absent 0, present with activity 1, present at rest 2) Urgency of the intervention (scheduled 0, elective 1, urgent 2, emergent 3) Respiratory distress (none 0, mild 1, mod 2, severe 3, extreme 4). For multiple anatomical sites (18 or more) in the upper airway, left and right sides, lesions are rated as 0=none, 1=surface lesion, 2=raised lesion, and 3=bulky lesion). A higher rating value indicates more advanced disease and a worse outcome.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
12-month Change in Voice Handicap Index (VHI) Score [ Time Frame: 2 months, and 12 months ]
Voice Handicap Index. This scale rates a patient's perception of voice related handicap in the domains of functional, physical, and emotional. There are 10 questions for each domain. Each question is rated by the subject on a 5-point scale, never =0, almost never =1, sometimes =2, almost always =3, always =4). A lower total score or domain score indicates improved, or less, voice handicap. Thus, the maximum total score is 4 X 30 = 120. For each domain, the maximum score is 4 X 10 = 40. Scores of 0 are the lowest possible score. In the paper we say that the Maximum score is 100, but obviously is it actually 120. Complete scale = 0-120. Lower score indicates improved perceived voice-realted quality of life.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Cidofovir for Recurrent Respiratory Papillomatosis
Official Title  ICMJE Use of Cidofovir Injection in the Treatment of Recurrent Respiratory Papillomatosis."
Brief Summary Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm of the larynx in the pediatric population. The impact of the disease on patients and families can be tremendous due to the need for frequent treatment. It would be highly beneficial to develop effective medical therapies as adjunctive measures to surgical ablation with the goal of reducing the frequency of reoccurrence.
Detailed Description

The focus of the present study is to evaluate the usefulness of cidofovir injection in diminishing the frequency and magnitude of papilloma recurrences in adult and pediatric RRP patients. Briefly, patients will be randomized into either a treatment (cidofovir injection) or a placebo group. The following measures will be made at each of 6 data collection time points, over the course of one year: (1) tumor load, based upon a published staging system for papilloma, (2) degree of respiratory obstruction for phonation, as assessed by phonation threshold pressures, and (3) general health, on validated health inventories (SF12 and Voice Handicap Index for adults; PedsQL (Trademarked) for children) and via measures of height weight and days absent from school or daycare, where applicable, for children. A repeated measures analysis will allow examination of time by treatment interactions to determine if the cidofovir injection group has fewer, or less severe, recurrences than the placebo group.

Specifically, we will answer the following questions in this investigation:

  1. Does cidofovir injection reduce the frequency of RRP recurrences?
  2. Does cidofovir injection reduce the magnitude of RRP, as assessed with a proposed staging system for RRP (Derkay et al., 1998) and measures of phonatory threshold pressure?
  3. Does cidofovir injection improve general health, as assessed by height, weight and days absent from school in pediatric patients and health inventories (general health and voice-related) in children and adults?
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Respiratory Papillomatosis
Intervention  ICMJE
  • Drug: Cidofovir
    With regard to cidofovir concentration, the FDA has allowed us to inject a concentration of 5 mg/ml into both children and adults. The injection will add less than 2 additional minutes to the surgery time and discharge time will not be affected. Because the volumes of cidofovir injected into the airway will be reasonably small (typically less than 2 mL), the total systemic dose of cidofovir administered per visit will be far below the FDA-approved systemic limit of 5 mg/kg for HIV-related CMV retinitis.
    Other Name: Vistide
  • Drug: Placebo
    On the baseline study day, patients will be randomized into either a treatment group (cidofovir injection) or a placebo group. A restricted randomization procedure, in groups of 4, will be used to encourage uniformity in sample sizes between groups.
    Other Name: Sugar pill
Study Arms  ICMJE
  • Active Comparator: Cidofovir
    Cidofovir (Vistide) is a commercially available agent approved by the FDA for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). The drug is not FDA approved for the treatment of RRP at this time. However, recent case reports have been encouraging with regard to the effectiveness of the agent in the treatment of RRP. The FDA has granted this study a "safe to proceed" designation with IND 58,481.
    Intervention: Drug: Cidofovir
  • Placebo Comparator: Placebo
    On the baseline study day, patients will be randomized into either a treatment group (cidofovir injection) or a placebo group. A restricted randomization procedure, in groups of 4, will be used to encourage uniformity in sample sizes between groups.
    Intervention: Drug: Placebo
Publications * McMurray JS, Connor N, Ford CN. Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled study. Ann Otol Rhinol Laryngol. 2008 Jul;117(7):477-83.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 24, 2010)
19
Original Enrollment  ICMJE
 (submitted: September 13, 2005)
20
Actual Study Completion Date  ICMJE December 2009
Actual Primary Completion Date December 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 4 surgeries for RRP in last 12 months

Exclusion Criteria:

  • Renal insufficiency
  • Nephrotoxic drugs in the last 7 days
  • Sulfa allergies
  • Currently treated with systemic or topical HPV chemotherapeutic agents
  • Females of childbearing potential with a positive pregnancy test
  • Women who are breast feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00205374
Other Study ID Numbers  ICMJE 1999-196
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: J. Scott McMurray, MD University of Wisconsin Medical School
PRS Account University of Wisconsin, Madison
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP