Recurrent Respiratory PapillomatosisPhase 4NCT00205374
Use of Cidofovir for Recurrent Respiratory Papillomatosis
A Phase 4 study testing Cidofovir in people with Recurrent Respiratory Papillomatosis, run by University of Wisconsin, Madison.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Recurrent Respiratory Papillomatosis
- What is being tested?
- Cidofovir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- Nov 1999to Dec 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 4 surgeries for RRP in last 12 months
Who cannot join
- 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
About this study
Official title: Use of Cidofovir Injection in the Treatment of Recurrent Respiratory Papillomatosis."
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.
Read the 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:
- Does cidofovir injection reduce the frequency of RRP recurrences?
- 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?
- 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?
- Conditions
- Recurrent Respiratory Papillomatosis
- Being tested
- Cidofovir, Placebo
- Medical subject headings
- Recurrent respiratory papillomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CidofovirDrug
Also called Vistide
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.
PlaceboDrug
Also called Sugar pill
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.
| Study group | Role | What they receive |
|---|---|---|
| Cidofovir | Active comparator | 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. Receives: Drug: Cidofovir |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Papilloma Severity
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.
Measured: Baseline, 2 months, and 12 months
Secondary outcomes (1)
12-month Change in Voice Handicap Index (VHI) Score
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.
Measured: 2 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startNov 1999
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Respiratory PapillomatosisStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- J. Scott McMurray, MD, Principal investigator, University of Wisconsin Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00205374
- Sponsor's protocol ID
- 1999-196
- Status last verified
- Feb 2019
- First submitted
- 13 Sep 2005
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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. doi: 10.1177/000348940811700702.
PubMed 18700421
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Cidofovir Injection in the Treatment of Recurrent Respiratory Papillomatosis."
- ClinicalTrials.gov ID
- NCT00205374
- Acronym / sponsor ID
- 1999-196
- Conditions
- Recurrent Respiratory Papillomatosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- Nov 1999
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 18 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does cidofovir injection reduce the frequency of RRP recurrences?
- 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?
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cidofovir | Active comparator | Drug: CidofovirCidofovir (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. |
| Placebo | Placebo comparator | Drug: PlaceboOn 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. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 4 surgeries for RRP in last 12 months
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CidofovirAlso: VistideWith 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. | Drug | Cidofovir |
| PlaceboAlso: Sugar pillOn 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 |
Primary outcome
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.
1 secondary outcome
12-month Change in Voice Handicap Index (VHI) Score
Time frame: 2 months, and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18700421McMurray 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. doi: 10.1177/000348940811700702.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. Scott McMurray, MD principal investigator
University of Wisconsin Medical School
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cidofovir in people with Recurrent Respiratory Papillomatosis, run by University of Wisconsin, Madison.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Papilloma Severity (time frame: Baseline, 2 months, and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00205374, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2019.