Nasally Delivered Pulmozyme for Sinusitis in Cystic Fibrosis

• Sponsor: University of Vermont (Other)
• Overall Status: Completed
• CT.gov ID: NCT00416182
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 66
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Chronic sinusitis is a frequent complication in cystic fibrosis. The aim of this study is to determine whether Pulmozyme(dornase alfa) would maintain sinus health (compared to placebo) in patients with cystic fibrosis who have recently undergone sinus surgery.

Condition or Disease	Intervention/Treatment	Phase
Sinusitis; Cystic Fibrosis	Drug: Pulmozyme (dornase alfa); Drug: Placebo	Phase 2

Detailed Description

AIM: To evaluate the effectiveness of Pulmozyme(dornase alfa) in decreasing post-operative sinusitis symptoms in patients with cystic fibrosis (CF)

PROCEDURES: 20 patients with CF will be randomized to receive either Pulmozyme or placebo via nasal inhalation daily for 12 months. Consent will be obtained following surgery and treatment will begin 1 week post-operatively.

Monitoring will include examination and recording of adverse effects and follow up weekly for one month and then at 2.5, 6, 9 and 12 months.

Outcome measures will include ciliary function testing, pulmonary function testing, sinus questionnaires and CT scan.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Use of Nasally Delivered Pulmozyme in the Treatment of Sinusitis in Cystic Fibrosis Patients: A Pilot Study
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pulmozyme 2.5 mg Pulmozyme (dornase alfa) delivered intranasally once daily	Drug: Pulmozyme (dornase alfa); 2.5 mg/2.5 mL of Pulmozyme (dornase alfa) delivered via Sinustar nasal nebulizer device; Other Names: Pulmozyme, dornase alfa, human recombinant DNase 1
Placebo Comparator: placebo 2.5 mg/2mL placebo administered intranasally once daily	Drug: Placebo; 2.5 mL of placebo delivered via Sinustar nebulizer device; Other Names: placebo comparator

Outcome Measures

Primary Outcome Measures

1. Computed Tomography Evidence of Less Sinus Disease [baseline and 1 year]

   compare sinus CT pre-op (baseline) to one year after initiation of study drug Difference in pre and post scores by Lund-McKay scoring system are reported (1 year minus baseline) The Lund-Mackay scoring system was used to evaluate the extent and severity of sinusitis. The scale ranges from 0 (best possible outcome with complete lucency of all sinuses) to 24 (worst possible outcome with complete opacification of all sinuses)

2. Improvement in Appearance of Nasal Passages/Sinuses [baseline and 1 year]

   periodic endoscopic photos of sinuses by ear-nose-throat (ENT) surgeon. The scale for scoring severity of disease ranges from 0 (best possible outcome) to 2 (worst possible outcome). independent blinded scoring by 2 surgeons difference in scores pre and post are reported (1 year minus baseline)

Secondary Outcome Measures

1. Chronic Sinusitis Survey Score [baseline and 1 year]

   pre-surgery and end of trial (12 months) Reduction in scores (baseline minus 1 year) are recorded The chronic sinusitis survey consists of 6 questions, ranges from 0-24, a lower score indicates the best possible outcome.

2. Pulmonary Function [baseline and 1 year]

   prior to surgery and end of study spirometry as measured by forced expiratory volume in 1 second (FEV1) percent predicted. The change over the course of the study (1 year minus baseline) is reported. A higher value indicates a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical and laboratory diagnosis of cystic fibrosis

• Age greater than or equal to 5 years

• Forced expiratory volume in 1 second (FEV1) greater than or equal to 40% predicted

• Sinus surgery within one week of enrollment

Exclusion Criteria:

• Pregnancy

• Intolerance of orally inhaled Pulmozyme (dornase alfa)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fletcher Allen Health Care	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• University of Vermont
• Genentech, Inc.

Investigators

• Principal Investigator: Thomas Lahiri, MD, University of Vermont
• Study Director: Sandra Diehl, MS, University of Vermont Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Thomas Lahiri, Professor of Pediatrics, University of Vermont
• ClinicalTrials.gov Identifier: NCT00416182
• Other Study ID Numbers: Z3297S
• First Posted: Dec 27, 2006
• Last Update Posted: Nov 14, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Thomas Lahiri, Professor of Pediatrics, University of Vermont: Cystic fibrosis; chronic sinusitis; mucolytic
• Additional relevant MeSH terms: Sinusitis; Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	Patients undergoing sinus surgery meeting inclusion criteria were approached in the outpatient or hospital setting
Pre-assignment Detail	upon providing informed consent, subjects were randomized and blinded to treatment or placebo groups

Arm/Group Title	Pulmozyme (Dornase Alfa)	Placebo
Arm/Group Description	2.5 mg/2.5mL of Pulmozyme administered intranasally once daily	2.5mg/2.5mL placebo administered intranasally once daily
Period Title: Overall Study
STARTED	8	8
COMPLETED	5	6
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Pulmozyme (Dornase Alfa)	Placebo	Total
Arm/Group Description	2.5 mg/2.5 mL of intranasal Pulmozyme	2.5 mL of placebo comparator	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	3 37.5%	6 75%	9 56.3%
Between 18 and 65 years	5 62.5%	2 25%	7 43.8%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 62.5%	5 62.5%	10 62.5%
Male	3 37.5%	3 37.5%	6 37.5%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Computed Tomography Evidence of Less Sinus Disease
Description	compare sinus CT pre-op (baseline) to one year after initiation of study drug Difference in pre and post scores by Lund-McKay scoring system are reported (1 year minus baseline) The Lund-Mackay scoring system was used to evaluate the extent and severity of sinusitis. The scale ranges from 0 (best possible outcome with complete lucency of all sinuses) to 24 (worst possible outcome with complete opacification of all sinuses)
Time Frame	baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pulmozyme	Placebo
Arm/Group Description	Patients receiving 2.5 mg intranasal Pulmozyme once daily	Patients receiving intranasal placebo once daily
Measure Participants	5	6
Mean (95% Confidence Interval) [units on a scale]	5.875	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pulmozyme, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments	P-value of < 0.05 is considered significant
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Improvement in Appearance of Nasal Passages/Sinuses
Description	periodic endoscopic photos of sinuses by ear-nose-throat (ENT) surgeon. The scale for scoring severity of disease ranges from 0 (best possible outcome) to 2 (worst possible outcome). independent blinded scoring by 2 surgeons difference in scores pre and post are reported (1 year minus baseline)
Time Frame	baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pulmozyme	Placebo
Arm/Group Description	endoscopic photos of sinuses by ENT surgeon independently and blindly scored by two surgeons with scale of 0,1,2 to indicate severity of disease	endoscopic photos of sinuses by ENT surgeon, independently and blindly scored by two surgeons. Scores of 0,1,2 based on disease severity.
Measure Participants	5	6
Mean (95% Confidence Interval) [units]	0.2	-1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pulmozyme, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments	P-value of < 0.05 is considered significant.
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Chronic Sinusitis Survey Score
Description	pre-surgery and end of trial (12 months) Reduction in scores (baseline minus 1 year) are recorded The chronic sinusitis survey consists of 6 questions, ranges from 0-24, a lower score indicates the best possible outcome.
Time Frame	baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pulmozyme	Placebo
Arm/Group Description	Scores from the Chronic Sinusitis Survey	Scores from the Chronic Sinusitis Survey recorded
Measure Participants	5	6
Mean (95% Confidence Interval) [units on a scale]	8.5	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pulmozyme, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value < 0.05 is considered significant
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Pulmonary Function
Description	prior to surgery and end of study spirometry as measured by forced expiratory volume in 1 second (FEV1) percent predicted. The change over the course of the study (1 year minus baseline) is reported. A higher value indicates a better outcome.
Time Frame	baseline and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pulmozyme	Placebo
Arm/Group Description	Percent predicted for forced expiratory volume in 1 second recorded	Percent predicted forced expiratory volume in 1 second recorded
Measure Participants	5	6
Mean (Full Range) [percentage of predicted FEV1]	0.8	5.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pulmozyme, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4
	Comments	P <0.05 is considered significant
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	1 year (study period)
Arm/Group Title	Pulmozyme		Placebo
Arm/Group Description	patients receiving once daily intranasal Pulmozyme		patients receiving once daily intranasal placebo
All Cause Mortality
	Pulmozyme		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pulmozyme		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		2/8 (25%)
Respiratory, thoracic and mediastinal disorders
hospitalization for pulmonary exacerbation	1/8 (12.5%)	1	2/8 (25%)	2
Other (Not Including Serious) Adverse Events
	Pulmozyme		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
sinus surgery	1/8 (12.5%)	1	0/8 (0%)	0

Limitations/Caveats

recruitment for a long trial was difficult so enrollment was truncated.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.