Trial Outcomes & Findings for Use of Cidofovir for Recurrent Respiratory Papillomatosis (NCT NCT00205374)

NCT ID: NCT00205374

Last Updated: 2019-02-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

19 participants

Primary outcome timeframe

Baseline, 2 months, and 12 months

Results posted on

2019-02-26

Participant Flow

The participants in this randomized, double-blind, placebo-controlled clinical trial were 19 consecutive adult or pediatric patients who presented to the University of Wisconsin Otolaryngology-Head and Neck Surgery Clinic with a diagnosis of RRP who met inclusio/exclusion criteria and gave informed consent to participate.

Before inclusion in this study, and 48 hours before each cidofovir injection, laboratory tests confirmed that the (female) participants were not pregnant and that laboratory findings were not exclusionary for study participation.

Participant milestones

Participant milestones
Measure
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. No more than 6 treatments were performed per patient within the 12-month time interval of the study.
Placebo
The placebo treatment was injection of saline solution that had a color and viscosity identical to those of the active drug. Up to 6 injections per participant were given during the study.
Overall Study
STARTED
10
9
Overall Study
COMPLETED
10
9
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Use of Cidofovir for Recurrent Respiratory Papillomatosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cidofovir
n=10 Participants
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.
Placebo
n=9 Participants
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.
Total
n=19 Participants
Total of all reporting groups
Age, Categorical
<=18 years
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
8 Participants
n=5 Participants
6 Participants
n=7 Participants
14 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
33 years
STANDARD_DEVIATION 18 • n=5 Participants
29 years
STANDARD_DEVIATION 12 • n=7 Participants
31 years
STANDARD_DEVIATION 15 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
8 Participants
n=7 Participants
16 Participants
n=5 Participants
Region of Enrollment
United States
10 participants
n=5 Participants
9 participants
n=7 Participants
19 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Cidofovir
n=10 Participants
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.
Placebo
n=9 Participants
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.
Change in Papilloma Severity
Baseline
13.2 scores on a scale
Interval 5.0 to 33.0
12 scores on a scale
Interval 5.0 to 23.0
Change in Papilloma Severity
2 months
3.7 scores on a scale
Interval 0.0 to 11.0
3.6 scores on a scale
Interval 1.0 to 11.0
Change in Papilloma Severity
12 months
2.7 scores on a scale
Interval 0.0 to 13.0
5.1 scores on a scale
Interval 0.0 to 16.0

SECONDARY outcome

Timeframe: 2 months, and 12 months

Population: \[raw data no longer exist for this study, there a no data to report for a Baseline measure\]

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.

Outcome measures

Outcome measures
Measure
Cidofovir
n=10 Participants
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.
Placebo
n=9 Participants
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.
12-month Change in Voice Handicap Index (VHI) Score
2 months
22 scores on a scale
Interval 0.0 to 59.0
32 scores on a scale
Interval 8.0 to 61.0
12-month Change in Voice Handicap Index (VHI) Score
12 months
31 scores on a scale
Interval 2.0 to 63.0
42 scores on a scale
Interval 0.0 to 93.0

Adverse Events

Cidofovir

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

J. Scott McMurray, MD

University of Wisconsin-Madison

Phone: 608-262-7181

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place