Effectiveness of Pulmozyme in Infants With Cystic Fibrosis

• Sponsor: Nationwide Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00179998
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 138
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study to find out whether Pulmozyme is effective for clearing mucus from the airways of children with cystic fibrosis less than 3 ½ years of age.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Recombinant Human DNase (Pulmozyme); Drug: Placebos	Phase 2

Detailed Description

Pulmozyme is given using a nebulizer and is now widely used in older children and adults with cystic fibrosis. In adults and older children, studies have shown that daily use of Pulmozyme improves lung function and decreases the number of lung infections requiring hospital treatment. Pulmozyme has been approved by the Food and Drug Administration for use in children over 5 years old and adults with cystic fibrosis. Pulmozyme has also been approved by the FDA for use in children with cystic fibrosis less than 5 years old based upon studies showing that it is safe in this age group and that it does get into the airway tubes as well in infants and toddlers as it does in older children and adults. Currently Pulmozyme is not widely used in children with cystic fibrosis younger than 5 years because no study has clearly shown that inhaling Pulmozyme daily improves lung function or improves clearance of mucus from the airway tubes in very young children. This study will measure whether Pulmozyme improves lung function and mucous clearance from the lungs in children with cystic fibrosis less than 3 ½ years of age.

This study will compare Pulmozyme to a placebo. During the study infants and young children with cystic fibrosis will be treated with Pulmozyme for 6 months and placebo for 6 months. The study medicines will be inhaled at home once a day from a nebulizer for a period of one year. Half of the children will be treated with Pulmozyme for the first 6 months of the study and half will receive the placebo. At the 6 month point the group receiving Pulmozyme will be changed to the placebo and the group receiving placebo will be changed to Pulmozyme. The order of the 6 month treatment periods is randomized. This study is blinded. The study doctor and his staff will not know who is receiving Pulmozyme or placebo at any time during the study.

Whether Pulmozyme works will be measured using infant lung function tests and by doing a special 3-D x-ray of the child's chest (a high resolution CT or HRCT) at the beginning of the study, at 6 months and at 12 month after starting study. The study will not change the regular clinical care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Pulmozyme in Infants and Young Children With Cystic Fibrosis
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Recombinant Human DNase (Pulmozyme) then Placebo once daily nebulized rhDNAse	Drug: Recombinant Human DNase (Pulmozyme); 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months; Other Names: Pulmozyme ; Drug: Placebos; 2.5 ml sterile solution (8.77 mg/ml sodium chloride, 0.15 mg/ml calcium chloride, pH 7.0 +/- 2.0) delivered daily by nebulization for 6 months, either preceding or following 6 months of Pulmozyme depending on randomization of the subject
Placebo Comparator: Placebo (Nebulized Saline) then rhDNase once daily nebulized vehicle	Drug: Recombinant Human DNase (Pulmozyme); 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months; Other Names: Pulmozyme ; Drug: Placebos; 2.5 ml sterile solution (8.77 mg/ml sodium chloride, 0.15 mg/ml calcium chloride, pH 7.0 +/- 2.0) delivered daily by nebulization for 6 months, either preceding or following 6 months of Pulmozyme depending on randomization of the subject

Outcome Measures

Primary Outcome Measures

1. Chest CT (High Resolution Computed Tomography (HRCT) Score) [6 months]

   Change in Total HRCT Score from initiation of intervention to 6 months Modified Maffessanti HRCT Scoring System Airways Bronchial Wall Thickening:1 = mild, 2 = moderate, 3 = severe Bronchiectasis:1 = mild, 2 = moderate, 3 = severe Axial extent of 1 or 2: 1 = central/middle, 2 = also periphery Regional extent of 1 or 2: x 1 if < 50 %, x 2 if > 50 % Gas trapping score:0 if 1 sub-segment, 1 if < 25 %, 2 if 25 - 50 %, 3 if 50 - 75 %, 4 if > 75 % Multiply (# 1 + # 2 + # 3) by # 4 then add # 5 Parenchyma Airspace disease: 0 = none, 1 = present Ground glass opacity: 0 = none, 1 = present Mucous Plugging: 0 = none, 1 = present Total Score = Airway + Parenchymal Scores for RUL, LUL, RLL, and LLL Sections. The Total Score ranges from 12 to 92, with higher scores indicating greater impairment. Maximum Score = 4 x 23 = 92

2. Infant Pulmonary Function Tests (FEV0.5) [6 months]

   Change in FEV0.5 from initiation of intervention to 6 months

Secondary Outcome Measures

1. Antibiotic Treatment Days [per 6 month interval]

   Total number of days treated with IV, oral or nebulized antibiotics over 6 initial month interval

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 30 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age < 30 months

• Diagnosis of CF based on clinical features consistent with CF as well as 1 of the 2 following criteria: a) two sweat chlorides >60 mEq/L (by quantitative pilocarpine iontophoresis), b) genotype with 2 identifiable mutations consistent with CF.

• Informed consent by parent or legal guardian

Exclusion Criteria:

• Previous treatment with Pulmozyme

• Hospitalization or treatment with IV antibiotics with 14 days of initial study visit

• Acute intercurrent respiratory infection, defined as any of the following symptoms within the preceding 48 hours: 1) fever > 38 degrees C, 2) new onset of coryza or other upper respiratory symptoms, 3) increase in cough, wheezing, or respiratory rate

• History of adverse reaction to sedation

• Oxyhemoglobin saturation <90% on room air

• Severe upper airway obstruction as determined by site PI (severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea)

• Hemodynamically significant congenital heart disease or diagnosed arrhythmias

• History of hemoptysis

• History of previous pulmonary air leak (pneumothorax)

• Diagnosed seizure disorder necessitating current anticonvulsive therapy. A history of febrile seizures is not an exclusion criterion.

• Use of Investigational drug(s) within 60 days or 5 half-lives of enrollment in this study.

• Known allergy to Chinese Hamster Ovary-derived biological products or any component of the placebo or active drug formulations.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nationwide Children's Hospital	Columbus	Ohio	United States	43205

Sponsors and Collaborators

• Nationwide Children's Hospital
• Genentech, Inc.

Investigators

• Principal Investigator: Robert G Castile, MD, The Research Institute at Nationwide Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT00179998
• Other Study ID Numbers: Z2910s
• First Posted: Sep 16, 2005
• Last Update Posted: May 9, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Nationwide Children's Hospital: Cystic fibrosis; Infants; Children; Pulmozyme; Pulmonary function; Computed tomography
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Arm/Group Title	1 - rhDNase Then Placebo	2 - Placebo Then rhDNase
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	once daily nebulized vehicle Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months
Period Title: Initial Period - 6 Months
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: Initial Period - 6 Months
STARTED	12	12
COMPLETED	12	10
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Nebulized rhDNAse Then Placebo	Placebo Then Nebulized rhDNAse	Total
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months then 3 ml diluent placebo delivered by nebulization given daily for 6 months	once daily nebulized vehicle Recombinant Human DNase (Pulmozyme): Comparison of 3 ml diluent placebo delivered by nebulization given daily for 6 months then 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months	Total of all reporting groups
Overall Participants	12	12	24
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	23.3 (11.9)	48.3 (36.7)	41.8 (31.6)
Sex: Female, Male (Count of Participants)
Female	4 33.3%	8 66.7%	12 50%
Male	8 66.7%	4 33.3%	12 50%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Chest CT (High Resolution Computed Tomography (HRCT) Score)
Description	Change in Total HRCT Score from initiation of intervention to 6 months Modified Maffessanti HRCT Scoring System Airways Bronchial Wall Thickening:1 = mild, 2 = moderate, 3 = severe Bronchiectasis:1 = mild, 2 = moderate, 3 = severe Axial extent of 1 or 2: 1 = central/middle, 2 = also periphery Regional extent of 1 or 2: x 1 if < 50 %, x 2 if > 50 % Gas trapping score:0 if 1 sub-segment, 1 if < 25 %, 2 if 25 - 50 %, 3 if 50 - 75 %, 4 if > 75 % Multiply (# 1 + # 2 + # 3) by # 4 then add # 5 Parenchyma Airspace disease: 0 = none, 1 = present Ground glass opacity: 0 = none, 1 = present Mucous Plugging: 0 = none, 1 = present Total Score = Airway + Parenchymal Scores for RUL, LUL, RLL, and LLL Sections. The Total Score ranges from 12 to 92, with higher scores indicating greater impairment. Maximum Score = 4 x 23 = 92
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Subjects will include children with CF < 30 months old and never treated with Pulmozyme. Patients available for recruitment will include 12 newly diagnosed children <30 months old from Nationwide Children's Hospital and 4 from Dayton Children's.

Arm/Group Title	Nebulized rhDNAse	Nebulized Saline
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	once daily nebulized vehicle
Measure Participants	12	12
Mean (Standard Deviation) [Score points]	3.7 (21.1)	6.1 (9.5)

2. Primary Outcome

Title	Infant Pulmonary Function Tests (FEV0.5)
Description	Change in FEV0.5 from initiation of intervention to 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Children < 30 months of age with cystic fibrosis who were given either the study drug followed by the placebo or given placebo followed by study drug. Data is not available for the second period, as the PI has retired and is no longer associated with NCH.

Arm/Group Title	Nebulized rhDNAse Then Placebo	Placebo (Nebulized Saline) Then rhDNAse
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	Once daily 3 ml diluent delivered by nebulization given daily for 6 months followed by 2.5 mg rhDNAse in 3 ml diluent delivered by nebulization given daily for 6 months
Measure Participants	12	12
Mean (Standard Deviation) [z score]	-0.1 (1.1)	-0.2 (1.0)

3. Secondary Outcome

Title	Antibiotic Treatment Days
Description	Total number of days treated with IV, oral or nebulized antibiotics over 6 initial month interval
Time Frame	per 6 month interval

Outcome Measure Data

Analysis Population Description

Subjects included children < 30 months of age who were newly diagnosed with Cystic Fibrosis. Subjects were recruited from Nationwide Children's (AKA Columbus Children's) and Dayton Children's Hospitals.

Arm/Group Title	Nebulized rhDNAse Then Placebo	Placebo (Nebulized Saline) Then rhDNAse
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent. IPFTs and CV-HRCT will be performed at that time. These subjects will then receive the placebo (Normal saline) delivered by nebulization given daily for 6 months. IPFT and CV-HRCTs will be performed again at 1 year.	Those placed in the placebo arm with receive nebulized normal saline daily for 6 months. Following evaluation by IPFT and CV-HRCT, these subjects will receive the study drug daily for 6 months by the same delivery method. IPFT and CT-HRCTs will be performed again at 1 year.
Measure Participants	12	12
Mean (Standard Deviation) [days]	31.7 (24.5)	36.3 (20.1)

Adverse Events

Time Frame	6 months for each intervention
Adverse Event Reporting Description	Safety population included all participants who received either the study drug or placebo
Arm/Group Title	Nebulized rhDNAse Then Placebo(Nebulized Saline)		Placebo (Nebulized Saline) Then rhDNAse
Arm/Group Description	once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.		Once daily nebulized saline daily for 6 months, followed by Recombinant Human DNase (Pulmozyme) in 3 ml diluent daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.
All Cause Mortality
	Nebulized rhDNAse Then Placebo(Nebulized Saline)		Placebo (Nebulized Saline) Then rhDNAse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebulized rhDNAse Then Placebo(Nebulized Saline)		Placebo (Nebulized Saline) Then rhDNAse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
wheezing	1/12 (8.3%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Nebulized rhDNAse Then Placebo(Nebulized Saline)		Placebo (Nebulized Saline) Then rhDNAse
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		11/12 (91.7%)
Respiratory, thoracic and mediastinal disorders
cough	11/12 (91.7%)	11	11/12 (91.7%)	11

Limitations/Caveats

Dr. Castile is retired and no longer is associated with Nationwide Children's Hospital and no one associated with the trial works at NCH any longer. We are unable to further update this study in clinicaltrials.gov.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.