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Use of Cidofovir for Recurrent Respiratory Papillomatosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00205374
First received: September 13, 2005
Last updated: June 19, 2017
Last verified: June 2017
  Purpose
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.

Condition Intervention Phase
Recurrent Respiratory Papillomatosis Drug: Cidofovir Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: Use of Cidofovir Injection in the Treatment of Recurrent Respiratory Papillomatosis."

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Change in Papilloma Severity [ Time Frame: 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.



Secondary Outcome Measures:
  • 12-month Reduction 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.



Enrollment: 19
Study Start Date: November 1999
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

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?
  Eligibility

Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00205374

Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: J. Scott McMurray, MD University of Wisconsin Medical School
  More Information

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00205374     History of Changes
Other Study ID Numbers: 1999-196
Study First Received: September 13, 2005
Results First Received: February 22, 2013
Last Updated: June 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Papilloma
Respiratory Tract Infections
Papillomavirus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Infection
Respiratory Tract Diseases
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Cidofovir
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 16, 2017